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[(sensitive)-524.9(shell-sheddable)-522.2(micelles,)-524(\(ii\))-517.2(reduction-sensitive)]TJ 0 -1.1174 TD [(disassembla)-10.8(ble)-286.8(micelles)-290.2(with)-293.5(a)-284.5(reductively)-292.4(degradable)-292.2(core,)]TJ 0 -1.1116 TD [(\(iii\))-380.2(reduction-sensitive)-382.9(reversibly)-382(shell-cross-linked)-386(\(SCL\))]TJ T* [(micelles,)-345.5(and)-338.5(\(iv\))-344.3(reduction-sensitive)-342.6(reversibly)-347.4(core-cross-)]TJ T* [(linked)-474.6(\(CCL\))-475.2(micelles)-480.3(\(Fig.)-474.3(1\).)-472.1(The)-472.2(versatile)-480.1(design)-474.2(and)]TJ ET q 1 i 126.822 544.762 m 487.389 544.762 l 487.389 182.891 l 126.822 182.891 l W n q 360.926 0 0 361.871 126.822 182.891 cm /Im2 Do Q Q BT /F7 1 Tf 9.845 0 0 9.845 62.022 166.1102 Tm [(FIG.)-238.8(1.)-994.8(Il)15.3(lu)21(st)21.2(ra)19.9(ti)20.9(on)-214.9(of)-215(re)18.7(du)15.6(ct)19.9(io)20.9(n-)21.2(se)20.1(ns)15.6(it)20.9(iv)20.9(e)-226.7(m)0(i)19.9(c)0(e)18.7(l)0(l)20.7(e)0(s)-216(f)0(o)21(r)-226.7(ac)19.9(ti)20.9(ve)-216.2(de)20.1(li)20.7(ve)19.9(ry)-216.2(of)-215(an)21.2(ti)15.1(ca)19.9(nc)20.1(er)-217.4(dr)20.1(ug)21.2(s.)-211.5(\(A)14.5(\))]TJ /F5 1 Tf 39.6015 0 TD [(Re)18.9(du)21.1(ct)19.7(io)20.9(n-)21(se)20(ns)15.5(it)20.7(iv)20.9(e)-226.8(s)0(h)21.2(e)0(l)19.7(l)0(-)]TJ -39.6015 -1.0135 TD [(sh)21.2(ed)19.9(da)14.1(bl)20.9(e)-278.6(m)0(i)19.7(c)0(e)18.7(l)0(l)20.7(e)0(s)-273.6(f)0(o)21(r)0(m)19.9(e)0(d)-268(f)0(r)21(o)0(m)-273.8(a)0(m)24.5(p)0(h)15.3(i)0(p)20.9(h)0(i)20.9(l)0(i)20.7(c)-278.6(bl)20.9(oc)14.1(k)-277.4(o)0(r)-266.9(g)0(r)21.1(a)0(f)14.1(t)-277.6(co)19.9(po)21.1(ly)20.9(me)18.7(rs)-272.5(co)19.9(nt)20.9(ai)19.7(ni)20.9(ng)-272.6(in)20.9(te)19.7(rv)21(en)19.9(in)20.9(g)-283.2(d)0(i)20.9(s)0(u)21.2(l)0()21(d)0(e)-273.8(b)0(o)21.1(n)0(d)21(s)-277.2(wo)20.2(ul)20.9(d)-283.2(q)0(u)21.1(i)0(c)19.7(k)0(l)20.9(y)]TJ 0 -1.0077 TD [(sh)21.2(ed)-469.6(of)21.1(f)-479(s)0(h)15.5(e)0(l)19.7(l)0(s)21(,)-475.6(di)20.9(sa)14.3(ss)21.4(em)18.7(bl)20.9(e,)-472(an)19.9(d)-473.2(f)0(o)15.3(r)0(m)-463.8(l)0(a)13.9(r)0(g)21(e)-480.1(ag)19.9(gr)21.1(eg)19.9(at)19.7(es)-469.4(un)21.1(de)19.9(r)-479(a)-480.1(re)19.9(du)21.1(ct)19.7(iv)15.1(e)-474.4(e)0(n)19.9(v)0(i)15.1(r)0(o)21(n)0(m)19.9(e)0(n)19.9(t)0(,)-465.2(r)0(e)19.9(s)0(u)15.5(l)0(t)20.7(i)0(n)20.9(g)-479(in)-468.6(fa)19.9(st)-468.4(an)19.9(d)-479(c)0(o)19.9(m)0(p)19.9(l)0(e)19.7(t)0(e)]TJ 0 -1.0135 TD [(in)20.9(tr)20.9(ac)12.9(el)19.7(lu)20.9(la)19.7(r)-300.4(d)0(r)21.1(u)0(g)-289.9(r)0(e)19.9(l)0(e)19.7(a)0(s)20.1(e)0(.)]TJ /F7 1 Tf 10.4172 0 TD [(\(B)20.1(\))]TJ /F5 1 Tf 1.6124 0 TD [(Re)18.9(du)21.1(ct)19.7(io)20.9(n-)15.3(se)20(ns)21.2(it)20.7(iv)20.9(e)-301.6(d)0(i)20.9(s)0(a)20.1(s)0(s)15.6(e)0(m)18.7(b)0(l)20.9(a)0(b)19.9(l)0(e)-291.3(m)0(i)19.7(c)0(e)18.7(l)0(l)20.7(e)0(s)-290.9(a)0(r)19.9(e)-301.6(pr)21.1(ep)19.9(ar)19.9(ed)-291.1(fr)15.3(om)-285.3(am)18.7(ph)21.1(ip)15.1(hi)20.9(li)20.7(c)-301.6(c)0(o)19.9(p)0(o)21.1(l)0(y)20.9(m)0(e)18.7(r)0(s)-289.7(w)0(i)20.1(t)0(h)-290.1(a)]TJ -12.0296 -1.0135 TD [(re)19.9(du)21.1(ct)19.7(iv)15.1(el)19.7(y)-317.7(d)0(e)14.1(g)0(r)21.1(a)0(d)19.9(a)0(b)19.9(l)0(e)-314.3(h)0(y)21.1(d)0(r)21.1(o)0(p)21.1(h)0(o)21.1(b)0(i)20.9(c)-324.6(bl)20.9(oc)19.9(k.)-315.3(Th)19.9(e)-318.9(m)0(i)19.7(c)0(e)18.7(l)0(l)20.7(e)0(s)-313.9(w)0(o)20.2(u)0(l)15.1(d)-317.7(sw)20.4(el)13.9(l)-317.9(a)0(n)19.9(d)-323.5(ev)19.9(en)19.9(tu)20.9(al)19.7(ly)-313.1(be)-314.1(di)20.9(si)21(nt)20.9(eg)14.1(ra)19.9(te)19.7(d)-317.7(i)0(n)15.1(s)0(i)21(d)0(e)-314.1(t)0(h)20.9(e)-318.9(tu)15.1(m)15.1(o)0(r)-313(c)0(e)18.7(l)0(l)20.7(s)0(,)]TJ T* [(gi)20.9(vi)20.9(ng)-336(ri)20.9(se)-331.2(to)-330.4(co)19.9(mp)19.9(le)19.7(te)-331.6(dr)21.1(ug)-336(re)19.9(le)19.7(as)20.1(e.)]TJ /F7 1 Tf 15.1392 0 TD [(\(C)20.2(\))]TJ /F5 1 Tf 1.7045 0 TD [(Re)18.9(du)21.1(ct)19.7(io)20.9(n-)15.3(se)20.1(ns)21.2(it)20.7(iv)20.9(e)-341.9(r)0(e)19.9(v)0(e)14.1(r)0(s)21.2(i)0(b)20.9(l)0(y)-330.4(S)0(C)20.2(L)-341.9(mi)19.7(ce)18.7(ll)20.7(es)14.3(,)-337.4(a)0(l)19.7(t)0(h)15.1(o)0(u)21.1(g)0(h)-330.2(r)0(o)21(b)0(u)21.1(s)0(t)-330.2(a)0(g)19.9(a)0(i)13.9(n)0(s)21.2(t)-340.9(di)20.9(lu)20.9(ti)20.7(on)21.1(,)-343.1(a)0(r)19.9(e)]TJ -16.8437 -1.0077 TD [(pr)21.1(on)21.1(e)-445.6(t)0(o)-439.8(f)0(a)19.9(s)0(t)-433.9(d)0(e)19.9(-)0(c)19.9(r)0(o)21(s)0(s)15.6(-)0(l)20.9(i)0(n)20.9(k)0(i)20.9(n)0(g)-433.9(a)0(n)19.9(d)-444.4(di)15.1(ss)21.4(oc)19.9(ia)19.7(ti)20.7(on)-433.9(at)-435.2(lo)15.1(w)-445.2(c)0(o)19.9(n)0(c)19.9(e)0(n)19.9(t)0(r)20.9(a)0(t)19.7(i)0(o)20.9(n)0(s)-439.5(\()]TJ /F9 1 Tf 29.311 0 TD (<)Tj /F5 1 Tf .7083 0 TD [(CM)19.2(C\))-434.9(in)-434.1(re)19.9(sp)21.2(on)21(se)-440.6(to)-434(th)20.9(e)-445.6(i)0(n)20.9(t)0(r)20.9(a)0(c)18.7(e)0(l)19.7(l)0(u)20.9(l)0(a)13.9(r)-444.4(re)19.9(du)21.1(ct)19.7(iv)20.9(e)]TJ -30.0193 -1.0135 TD [(co)19.9(nd)21.1(it)20.7(io)15.1(n,)-465(el)19.7(eg)14.1(an)19.9(tl)20.7(y)-479(r)0(e)19.9(s)0(o)21.2(l)0(v)20.9(i)0(n)15.1(g)-479(th)20.9(e)-480.1(e)0(x)19.9(t)0(r)20.9(a)0(c)18.7(e)0(l)19.7(l)0(u)20.9(l)0(a)19.7(r)-479(st)15.3(ab)19.9(il)20.7(it)20.7(y)-479(a)0(n)19.9(d)-479(in)20.9(tr)15.1(ac)18.7(el)19.7(lu)20.9(la)19.7(r)-479(d)0(r)21(u)0(g)-468.4(r)0(e)14.1(l)0(e)19.7(a)0(s)20.1(e)-480.1(di)20.9(le)19.7(mm)18.7(a.)]TJ /F7 1 Tf 40.1601 0 TD [(\(D)20.2(\))]TJ /F5 1 Tf 1.8427 0 TD [(Re)18.9(du)21.1(ct)19.7(io)20.9(n-)21.1(se)14.3(ns)21.2(it)20.7(iv)20.9(e)]TJ -42.0028 -1.0135 TD [(re)19.9(ve)19.9(rs)15.5(ib)20.9(ly)-249.8(CC)19.1(L)-267.1(m)0(i)19.7(c)0(e)18.7(l)0(l)20.7(e)0(s)20.1(,)-262.5(al)19.7(th)15.1(ou)21.1(gh)-249.6(st)15.3(ab)19.9(le)-250.9(ag)19.9(ai)19.7(ns)15.5(t)-260.3(d)0(i)20.9(l)0(u)15.1(t)0(i)20.7(o)0(n)21.1(,)-262.5(ar)19.9(e)-267.1(s)0(u)21.2(b)0(j)20.9(e)0(c)18.7(t)-266.1(to)-249.8(de)19.9(-c)19.9(ro)15.3(ss)21.4(-l)20.9(in)20.9(ki)20.9(ng)15.3(,)-262.5(m)0(i)19.7(c)0(e)18.7(l)0(l)20.7(e)-261.3(sw)14.6(el)19.7(li)20.7(ng)21(,)-262.5(a)0(n)19.9(d)-265.9(di)20.9(ss)21.4(oc)19.9(ia)19.7(ti)14.9(on)-249.6(at)]TJ T* -.0192 Tc [(l)-19.2(o)1.7(w)-435.6(c)-19.2(on)-19.2(ce)-19.2(nt)-19.2(ra)-19.2(ti)-19.2(on)-19.2(s)-424.1(\()]TJ /F9 1 Tf 8.5226 0 TD 0 Tc (<)Tj /F5 1 Tf .7083 0 TD [(CM)19.2(C\))-406.1(un)21.1(de)19.9(r)-415.6(a)-416.8(re)19.9(du)21.1(ct)19.7(iv)20.9(e)-416.8(e)0(n)19.9(v)0(i)20.9(r)0(o)15.3(n)0(m)19.9(e)0(n)19.9(t)0(,)-401.9(w)0(h)20.2(i)0(c)19.7(h)-415.6(re)19.9(pr)15.3(es)20.1(en)19.9(ts)-405.1(th)20.9(e)-416.8(o)0(t)20.9(h)0(e)19.9(r)-415.6(wa)19.1(y)-415.6(t)0(o)-405.3(a)0(d)19.9(d)0(r)21(e)0(s)20(s)-415.4(th)15.1(e)-411(e)0(x)19.9(t)0(r)15.1(a)0(c)18.7(e)0(l)19.7(l)0(u)20.9(l)0(a)19.7(r)]TJ -9.2309 -1.0077 TD [(st)21(ab)19.9(il)14.9(it)20.7(y)-386.8(a)0(n)19.9(d)-392.6(in)20.9(tr)20.9(ac)18.7(el)19.7(lu)20.9(la)13.9(r)-386.8(d)0(r)21.1(u)0(g)-382(r)0(e)19.9(l)0(e)19.7(a)0(s)20.1(e)-393.7(di)20.9(le)19.7(mm)18.7(a.)-379.8(CM)19.2(C,)-379.7(cr)19.9(it)20.7(ic)19.7(al)-383.4(mi)19.7(ce)18.7(ll)20.7(e)-388(c)0(o)19.9(n)0(c)14.1(e)0(n)19.9(t)0(r)20.9(a)0(t)19.7(i)0(o)20.9(n)0(;)-382.2(C)0(C)19.1(L)0(,)-379.8(c)0(o)19.9(r)0(e)19.9(-)0(c)19.9(r)0(o)21(s)0(s)15.6(-)0(l)20.9(i)0(n)20.9(k)0(e)19.9(d)0(;)-382.2(S)0(C)20.2(L)0(,)-379.8(s)0(h)21.2(e)0(l)19.7(l)0(-)]TJ 0 -1.0135 TD [(cr)19.9(os)21.2(s-)15.5(li)20.7(nk)21.1(ed)19.9(.)-245.2(T)0(o)-233.5(s)0(e)14.3(e)-244(th)20.9(is)-232.3(il)14.9(lu)20.9(st)21(ra)19.9(ti)20.7(on)-238.1(in)-232.5(co)19.9(lo)20.9(r,)-234.7(th)20.9(e)-249.8(r)0(e)19.9(a)0(d)19.9(e)0(r)-233.5(i)0(s)-238.1(r)0(e)19.9(f)0(e)19.9(r)0(r)21(e)0(d)-239.3(t)0(o)-232.5(t)0(h)20.9(e)-244(we)13.3(b)-242.9(v)0(e)19.9(r)0(s)21.2(i)0(o)20.9(n)-248.6(of)-232.3(th)20.9(is)-238.1(ar)19.9(ti)20.7(cl)19.7(e)-244(a)0(t)-239.4(w)0(w)19.4(w)0(.)17.8(l)0(i)20.7(e)0(b)19.9(e)0(r)19.9(t)0(p)20.9(u)0(b)21(.)0(c)17.5(o)0(m)19.9(/)0(a)19.7(r)0(s)]TJ /F3 1 Tf 8.9663 0 0 8.9663 62.022 749.6502 Tm (756)Tj 49.0026 0 TD [(SUN)-332.3(ET)-338.7(AL.)]TJ ET endstream endobj 87 0 obj << /Length 43 /Filter /FlateDecode >> stream xS**T0T0BiU)D* 9V endstream endobj 88 0 obj << /Type /XObject /Resources << /ProcSet [/PDF /Text /ImageB /ImageC /ImageI] /Font << /F1 754 0 R >> >> /Subtype /Form /BBox [0 0 612 792] /Matrix [1 0 0 1 0 0] /Length 54 /FormType 1 /Filter 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[(HepG2)-377(cells,)-379.9(resulting)-379.9(in)-370.9(high)-378.9(antitumor)-375.5(efcacy.)-378.5(Further-)]TJ 0 -1.1116 TD [(more,)-419.1(DOX-loaded)-419.2(SSPAA-)]TJ /F6 1 Tf 11.7383 0 TD (g)Tj /F5 1 Tf .5011 0 TD [(-PEG)-415.2(micelles)-416.9(exhibited)-415.8(sig-)]TJ -12.2394 -1.1116 TD [(nicantly)-381.1(stronger)-378.5(accumulation)-376.6(at)-377.9(the)-373.2(tumor)-375.5(site,)-377.7(reduced)]TJ T* [(distribution)-290.1(in)-284.6(normal)-291.3(organs,)-287.4(lower)-289.9(side)-287.7(effects,)-291(and)-286.7(higher)]TJ 0 -1.1174 TD [(antitumor)-248.8(efcacy)-248.3(compared)-243.9(to)-244.2(free)-248.6(DOX)]TJ /F11 1 Tf 16.7607 0 TD ($)Tj /F5 1 Tf .4493 0 TD [(HCl)-247.2(in)-238.5(nude)-247.5(mice)]TJ -17.21 -1.1116 TD [(bearing)-217.5(4T1)-217.6(breast)-216.2(carcinoma)-217.5(tumor)-214.2(xenograft)-219.7(\(66\).)-215.1(SSPAA-)]TJ /F6 1 Tf T* (g)Tj /F5 1 Tf .5011 0 TD [(-PEG/CPT)-335.4(prodrug)-330.2(micelles)-330.5(showed)-331(enhanced)]TJ /F6 1 Tf 19.3411 0 TD [(in)-330.6(vitro)]TJ /F5 1 Tf 3.3349 0 TD (re-)Tj -23.1771 -1.1174 TD [(lease)-331.5(of)-330.5(CPT)-327.9(at)-331.8(higher)-330.4(DTT)-329.1(concentration)-330.4(\(20\).)-330.3(Nam)]TJ /F6 1 Tf 22.2037 0 TD [(et)-331.8(al.)]TJ /F5 1 Tf -22.2037 -1.1116 TD [(found)-333.8(that)-328.4(reduction-sensitive)-336.8(SSPAA-)]TJ /F6 1 Tf 15.8968 0 TD (g)Tj /F5 1 Tf .5011 0 TD (-arginine/SS-\(PEG-)Tj -16.3979 -1.1116 TD [(PTX\))-392.2(prodrug)-393.6(micelles)-393.9(could)-392.7(efciently)-394.8(condense)-392.3(plasmid)]TJ 0 -1.1174 TD [(DNA)-253.6(into)-252.3(polyplexes)-255.3(with)-253.2(sizes)-255.2(ranging)-250.9(from)-253.2(125)-251(to)-250(210)-164.6(nm)]TJ 0 -1.1116 TD [(\(53\).)-353.4(These)-348.7(polyplexes)-353.2(displayed)-352.1(improved)-351.1(transfection)-350.9(ef-)]TJ T* [(ciency)-443.1(than)-443.4(25)-169.2(kDa)-443.1(bPEI,)-440.8(enhanced)-439.7(cellular)-444.6(uptake)-446.8(than)]TJ T* (SSPAA-)Tj /F6 1 Tf 3.427 0 TD (g)Tj /F5 1 Tf .5011 0 TD [(-arginine/DNA)-330.6(polyplexes,)-327.9(and)-327(had)-327(higher)-324.7(antitu-)]TJ -3.9281 -1.1174 TD [(mor)-511.4(potency)-505.5(than)-506.8(free)-513.5(PTX.)-504(Reduction-s)-9.8(ensitive)-506.7(polyion)]TJ 0 -1.1116 TD [(micelles)-595.5(obtained)-593.1(from)-587.3(SSPAA-)]TJ /F6 1 Tf 13.9558 0 TD (g)Tj /F5 1 Tf .5011 0 TD [(-PCL)-593.9(and)-586.2(PEG-COOH)]TJ -14.4569 -1.1116 TD [(showed)-521.1(a)-514.9(DTT-dependent)-522.3(PTX)-517.8(release)-524.9(prole,)-518(in)-514.9(which)]TJ 0 -1.1174 TD [(about)-191.1(30%,)-186.4(75%,)-186.4(and)-183(100%)-184(of)-186.5(PTX)-189.5(was)-189.5(released)-186.2(within)-186.4(9)-168.1(h)-185.4(in)]TJ 0 -1.1116 TD [(response)-609.7(to)-601.3(0,)-597.8(10,)-604.6(and)-597.7(40)-169.2(m)]TJ /F6 1 Tf 12.6886 0 TD (M)Tj /F5 1 Tf 1.4342 0 TD [(DTT,)-603.3(respectively)-605.5(\(26\).)]TJ -14.1228 -1.1116 TD .012 Tc [(Reducti)5(on)5.1(-sens)5.3(i)-.7(t)5(i)-.7(ve)-1078.8(micell)5(es)-1077.5(were)-1078.8(al)5(so)-1077.7(co)5.1(nst)5(r)-.6(u)5.1(c)-1.8(ted)]TJ 0 -1.1174 TD [(fro)5.2(m)-871.5(a)-1.7(mph)5.2(i)-.6(p)5.2(h)-.5(i)5.1(lic)-871.4(h)5.2(y)-.5(p)5.2(e)-1.7(rb)5.2(ranched)-876(h)5.2(omop)5.2(ol)5.1(yp)5.2(hos)5.4(ph)5.2(at)5.1(es)]TJ 0 -1.1116 TD .0117 Tc [(\(HP)5(H)-1.8(S)5(E)-2.1(P)5(s)-.7(\))-415.6(w)-1.8(i)4.7(t)-1(h)-415.6(d)4.8(isu)4.8(l)-1()5(d)-.9(e)-416.8(b)4.8(ond)4.8(s)-415.4(i)-1(n)-415.6(t)4.7(he)-416.8(b)4.8(a)-2.1(ckbo)4.8(ne,)-417.9(w)4(hich)]TJ T* .0123 Tc [(were)-370.1(pr)5.5(ep)5.4(ared)-368.9(by)-368.9(self)5.5(-cond)5.4(en)5.4(si)5.3(ng)-368.9(ri)5.3(ng-)5.5(op)5.4(en)5.4(in)5.4(g)-374.7(p)5.4(ol)5.3(ymer)5.5(i-)]TJ 0 -1.1174 TD .0124 Tc [(zatio)5.5(n)-685.6(o)-.2(f)-685.6(2-\()5.6(\(2)5.5(-hy)5.5(dr)5.6(ox)5.5(yet)5.4(h)-.2(y)5.5(l)-.3(\))5.6(-di)5.4(su)5.5(lfany)5.5(l)-.3(\))-685.6(e)-1.4(t)5.4(h)-.2(o)5.5(xy-)5.6(2-)5.6(ox)5.5(o-)]TJ 0 -1.1116 TD .0119 Tc [(1,3,2)5(-di)4.9(ox)5(ap)5(ho)5(sph)5(o)-.7(l)4.9(a)-1.9(n)5(e)-1153.8(\()5.1(4)-.7(3)5(\))-.7(.)-1149.2(D)-1.6(OX-)5.1(l)-.8(o)5(a)-1.9(d)5(e)-1.9(d)-1146.9(H)-1.6(P)5.2(H)-1.6(SEP)]TJ T* .013 Tc [(mi)6(ce)5(lle)5(s)-396.8(e)5(xh)6.1(ib)6.1(ite)5(d)-397(e)5(nh)6.1(an)6.1(ce)5(d)-397(c)5(el)6(l)-397.2(i)6(nhi)6(bi)6(ti)6(on)-391.3(aga)5(i).3(n)6.1(s).6(t)-391.4(G)-.5(S)6.3(H)-.5(-)]TJ T* .0134 Tc [(OE)5.4(t-p)6.5(r).8(e)5.4(t).7(r)6.6(e)-.4(a)5.4(t).7(ed)-298.7(He)5.4(La)-299.9(ce)5.4(ll)6.4(s)-304.3(\().8(I)6.6(C)]TJ 7.3823 0 0 6.5614 183.3448 175.5779 Tm .0145 Tc (50)Tj /F9 1 Tf 9.843 0 0 9.843 192.5858 177.222 Tm 0 Tc (=)Tj /F5 1 Tf .7257 0 TD .0109 Tc [(0.0)4(8)]TJ /F10 1 Tf 1.9583 0 TD 0 Tc (l)Tj /F5 1 Tf .5587 0 TD .0072 Tc [(g)-5.4(/)-5.5(ml)-5.5(\))-304.9(a)-6.6(nd)-310.7(re)-6.6(du)-5.4(c)-6.6(e)-.8(d)]TJ -16.7377 -1.1174 TD .007 Tc [(i)-5.7(n)-5.6(hi)-5.7(bi)-5.7(ti)-5.7(on)-598.9(t)-5.7(o)-5.6(wa)-6.8(rd)-598.9(b)-5.6(u).1(t)-5.7(h).1(i)-5.7(o)-5.6(ni)-5.7(ne)-600(s)-5.4(u).1(l)-5.7(f)-5.6(ox)-5.6(im)-6.8(in)-5.6(e-)-5.6(p)-5.6(r).2(e)-6.8(t)0(r)-5.6(e)-1(a)-6.8(t)0(e)-6.8(d)-598.9(\()-5.6(a)-1(n)]TJ 0 -1.1116 TD .0125 Tc [(inh)5.6(i)-.2(b)5.6(i)-.2(t)5.5(o)-.1(r)-627.9(for)-627.9(th)5.6(e)-634.8(i)5.5(ntr)5.7(a)-1.3(cel)5.5(l)-.2(u)5.6(l)-.2(ar)-627.9(sy)5.6(nt)5.5(hes)5.8(i)-.2(s)-627.7(o)-.1(f)-633.6(G)4.8(SH\))-633.7(c)4.5(el)5.5(ls)]TJ T* (\(IC)Tj 7.3823 0 0 6.5614 73.1905 142.696 Tm .0145 Tc (50)Tj /F9 1 Tf 9.843 0 0 9.843 82.4315 144.3401 Tm 0 Tc (=)Tj /F5 1 Tf .7315 0 TD .0081 Tc [(0.6)-4.5(4)]TJ /F10 1 Tf 1.9525 0 TD 0 Tc (l)Tj /F5 1 Tf .5645 0 TD .0072 Tc [(g/)-5.5(ml)-5.5(\))-840.5(c)-6.6(om)-6.6(pa)-6.6(re)-6.6(d)-840.6(t).2(o)-846.3(t).2(h)-5.4(e)-841.7(no)-5.4(nt)-5.5(r)-5.4(e)-.8(a)-6.6(t).2(e)-6.6(d)-840.6(ce)-6.6(ll)-5.5(s)]TJ -5.5524 -1.1174 TD .0126 Tc (\(IC)Tj 7.3823 0 0 6.5614 73.1905 131.6976 Tm .0145 Tc (50)Tj /F9 1 Tf 9.843 0 0 9.843 82.4315 133.3417 Tm 0 Tc (=)Tj /F5 1 Tf .7315 0 TD .0081 Tc [(0.3)-4.5(5)]TJ /F10 1 Tf 1.9525 0 TD 0 Tc (l)Tj /F5 1 Tf .5645 0 TD .0121 Tc [(g)5.2(/)-.6(ml\).)-434.8(In)-438.3(a)-439.4(p)-.5(r)5.3(e)-1.7(v)5.2(i)-.6(ou)5.2(s)-438.1(s)-.3(tu)5.2(dy)5.2(,)-440.6(i)-.6(t)-438.4(w)4.4(as)-438.1(ob)5.2(served)]TJ -5.5524 -1.1116 TD [(that)-484.6(amphi)5(ph)5.1(il)5(ic)-479.8(hyp)5.1(er)5.2(br)5.2(an)5.1(ched)-478.7(mu)5.1(lti)5(ar)5.2(m)-485.7(H)4.3(PHSEP-)]TJ /F6 1 Tf 22.3707 0 TD .0068 Tc [(st)-5.9(ar)]TJ /F5 1 Tf 1.5897 0 TD 0 Tc (-)Tj -23.9604 -1.1116 TD .0115 Tc [(PEP)-386.9(c)-2.3(o)4.6(p)-1.1(o)4.6(l)-1.2(y)4.6(pho)4.6(sp)4.6(hate-)4.7(b)-1.1(ased)-387(micell)4.5(es)-386.8(d)4.6(e)-2.3(creas)4.8(e)-2.3(d)-387(f)4.7(ro)4.6(m)-388.2(7)4.6(0)]TJ 0 -1.1174 TD .0123 Tc [(100)-161.6(nm)-272.2(to)-276.8(10)-161.6(nm)-278(aft)5.3(e)-1.5(r)-276.7(4)-.3(8)-161.6(h)-276.8(in)5.4(cu)5.4(batio)5.4(n)-276.8(i)-.4(n)-276.8(1)5.4(0)-167.3(m)]TJ /F6 1 Tf 18.9552 0 TD 0 Tc (M)Tj /F5 1 Tf 1.1231 0 TD .0135 Tc [(DT)5.5(T)-276.8(\().9(4)6.6(6).9(\))6.7(.)]TJ -20.0783 -1.1116 TD .0115 Tc [(Mo)4.6(reo)4.6(v)-1.1(er,)-487.3(D)-2(OX-l)4.5(oaded)-490.7(m)-2.3(i)4.5(c)-2.3(elles)-490.5(w)-2(ere)-491.8(s)4.8(hown)-490.7(t)-1.2(o)-490.7(r)4.7(ap)4.6(id)4.6(ly)]TJ T* .0072 Tc [(r)-5.4(e)-6.6(le)-6.6(as)-5.2(e)-467.4(D)-6.3(OX)-472.8(in)-5.4(to)-471.9(th)-5.4(e)-467.4(n)-5.4(uc)-6.6(l)-5.5(e)-.8(i)-472.1(o).3(f)-471.9(H)-.5(e)-6.6(L)-.8(a)-473.1(c)-.8(e)-6.6(l).2(l)-5.5(s).5(,)-468.5(r)-5.4(e)-6.6(s).5(u)-5.4(l).2(t)-5.5(i).2(n)-5.4(g)-466.2(i)-5.5(n)]TJ 0 -1.1174 TD .0131 Tc [(en)6.2(han)6.2(c)-.7(e)5.1(d)-725.2(an)6.2(ti)6.1(tu)6.2(mo)6.2(r)-725.2(e)-.7(f)6.4(ca)5.1(cy)6.2(.)-727.6(M)5.3(ul)6.1(tic)5.1(or)6.3(e/)6.1(she)5.1(l).4(l)6.1(-).5(st)6.1(ru)6.2(ct)6.1(ure)5.1(d)]TJ 0 -1.1116 TD .0118 Tc [(red)4.9(u)-.8(cti)4.8(o)-.8(n)4.9(-)-.8(sens)5.1(iti)4.8(ve)-906.2(mi)4.8(cell)4.8(es)-910.7(con)4.9(s)-.6(tr)5(ucted)-910.8(f)-.8(r)5(o)-.8(m)-906.3(h)-.8(y)4.9(p)-.8(er-)]TJ 25.5097 67.9184 TD .0124 Tc [(b)5.5(r)-.2(anch)5.5(ed)-386.1(p)5.5(o)-.2(ly)5.5(di)5.4(selen)5.5(i)-.3(d)5.5(e)-387.3(pos)5.7(sessi)5.4(ng)-386.1(al)5.4(tern)5.5(ati)5.4(v)-.2(e)-387.3(h)5.5(ydr)5.6(op)5.5(ho)5.5(-)]TJ 0 -1.1174 TD .0071 Tc [(bi)-5.6(c)-260.1(d).2(i)-5.6(s).4(e)-6.7(l).1(e)-6.7(n).2(i)-5.6(d)-5.5(e)-254.3(b)-5.5(on)-5.5(ds)-258.8(a)-6.7(n).2(d)-258.9(h)-5.5(yd)-5.5(ro)-5.5(ph)-5.5(i)-5.6(l).1(i)-5.6(c)-254.3(p)-5.5(h).2(o)-5.5(s)-5.3(ph)-5.5(at)-5.7(e)-254.3(m)-6.7(oi)-5.6(et)-5.6(i)-5.6(e)-.9(s)-258.8(i).1(n)]TJ 0 -1.1116 TD .0114 Tc [(t)4.4(h)-1.2(e)-526.5(b)4.5(ackb)4.5(one)-520.8(framewo)4.5(rk)-525.3(d)4.5(i)-1.3(s)4.7(p)-1.2(layed)-525.3(f)-1.2(ast)-525.5(r)4.6(esp)4.5(o)-1.2(n)4.5(s)-1(e)-526.5(t)4.4(o)-525.4(r)-1.2(e-)]TJ T* .0117 Tc [(d)4.8(u)-.9(ctiv)4.8(e)-434.1(a)-2.1(gent)4.7(s)-438.5(a)3.7(nd)-432.9(achi)4.7(ev)4.8(ed)-432.9(rapid)-432.9(D)-1.8(OX)-433.8(rel)4.7(e)-2.1(ase)-434.1(i)-1(n)4.8(t)-1(o)-432.9(t)-1(h)4.8(e)]TJ T* .0091 Tc [(nuclei)-355(of)-354.8(He)-4.7(La)-356(ce)-4.7(lls)-348.9(\()-3.5(44\).)]TJ 1.0137 -1.1174 TD 0 Tc [(Reduction-sensitive)-499.2(core-degradable)-501.6(micelles)-497.5(have)-496.3(also)]TJ -1.0137 -1.1116 TD [(been)-323.5(designed)-327.9(from)-322.3(amphiphilic)-327.2(copolymers)-325.5(bearing)-321.2(multi-)]TJ T* [(ple)-229.2(disulde)-228.8(bonds)-224.2(at)-228.1(the)-229.2(side)-224.4(chain)-232.6(of)-226.8(hydrophobic)-226.5(regimen.)]TJ 0 -1.1174 TD [(For)-325.6(example,)-327(Ryu)]TJ /F6 1 Tf 7.6777 0 TD [(et)-326(al.)]TJ /F5 1 Tf 2.4133 0 TD [(prepared)-323.3(poly\(acrylic)-328.1(acid\)-)]TJ /F6 1 Tf 11.3524 0 TD (g)Tj /F5 1 Tf .5011 0 TD (-\(trie-)Tj -21.9445 -1.1116 TD [(thylene)-505.6(glycol)-509.1(monoethyl)-507.9(ether)-509(acrylate\)/\(undecyl)-511.1(dithio-)]TJ T* 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0 TD .0196 Tc [(compared)-465.3(to)-465.3(fre)-5.7(e)-460.7(D).4(O)-5.4(X)-460.4(and)-459.5(N).4(C)-5.6(L)-460.7(mic)-5.7(e).1(lles.)]TJ -5.3911 -1.1116 TD .0189 Tc [(Sa)-6.4(mara)-6.4(jeew)-6.1(a)]TJ /F6 1 Tf 5.8864 0 TD [(et)-316.3(al.)]TJ /F5 1 Tf 2.4824 0 TD .0186 Tc [(r)-5.5(e)-.9(po)-5.5(rte)-6.7(d)-310.8(th)-5.5(at)-310.9(r)-5.5(e)-.9(du)-5.5(ctio)-5.5(n-s)-5.3(e)-.9(ns)-5.3(iti)-5.7(ve)-312(S)-5.4(C)-.8(L)]TJ -8.3689 -1.1116 TD .0188 Tc [(mi)-5.5(cell)-5.5(e)-.7(s)-310.4(s)-5.1(elf)-5.3(-).5(as)-5.1(sem)-6.6(b).4(led)-316.4(f).5(r)-5.3(o).4(m)-311.8(p).4(o)-5.3(l).3(y\()-5.3(oli)-5.5(go\()-5.3(ethy)-5.3(len)-5.3(e)-311.8(gl)-5.5(ycol)-5.5(\))]TJ 0 -1.1174 TD [(met)-5.5(hyl)-771.5(e)-6.5(t).3(her)-771.3(a)-6.5(cryl)-5.5(ate)-6.5(-)]TJ /F6 1 Tf 10.2638 0 TD .0195 Tc (co)Tj /F5 1 Tf .9849 0 TD 0 Tc (-)Tj /F6 1 Tf .3571 0 TD (N)Tj /F5 1 Tf .6854 0 TD .0185 Tc [(-a)-6.8(cry)-5.6(l)0(oyl)-5.8(oxy)-5.6(suc)-6.8(c)-1(ini)-5.8(m)-1.1(ide)-6.8(\)).2(-)]TJ /F6 1 Tf 11.145 0 TD 0 Tc (b)Tj 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-1.1116 TD .0199 Tc [(show)-5.1(ed)-649.3(re)-5.4(markable)-650.5(cell)-655.2(i)1.4(nh)]TJ 12.7289 0 TD .0185 Tc [(ibit)-5.8(ion)-656.5(e)-1(ffe)-6.8(ct,)-653.1(w)-.7(i)-5.8(t)0(h)-650.7(a)-1(b)-5.6(out)]TJ -12.7289 -1.1116 TD .0235 Tc [(th)5.1(r)5.2(e)-1.8(ef)5.2(ol)5(d)-288.6(l)5(o)5.1(w)4.3(er)-282.8(IC)]TJ 7.3823 0 0 6.5614 389.9338 427.5778 Tm .0299 Tc (50)Tj 9.843 0 0 9.843 400.592 429.2219 Tm .0188 Tc [(val)-5.5(u).4(e)-288.7(t)-5.5(han)-293.3(f).5(r)-5.3(e)-.7(e)-288.7(P)-5.2(TX)-294.2(in)-287.6(K)-6.2(B)-288.6(c)-6.5(e)-.7(lls)-293.1(f)-5.3(o).4(l-)]TJ -8.893 -1.1116 TD [(l)-5.5(o).4(wi)-5.5(ng)-212.7(2)-166.6(h)-212.7(inc)-6.5(ubat)-5.5(i).3(on)-212.7(an)-5.3(d)]TJ /F12 1 Tf 10.8974 0 TD 0 Tc (*)Tj /F5 1 Tf 1.0195 0 TD .0218 Tc [(11)3.4(-)3.5(f)-2.3(o)3.4(l)3.3(d)-209.7(l)3.3(ower)-209.7(I)3.5(C)]TJ 7.3823 0 0 6.5614 498.614 416.6361 Tm .0222 Tc (50)Tj 9.843 0 0 9.843 508.4786 418.2802 Tm .0189 Tc [(than)-212.6(Ta)-6.4(xol)]TJ -19.8537 -1.1174 TD .0222 Tc 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[(demonstrate)-5.6(d)-384.6(enha)-5.6(nced)-384.6(a)-5.6(n)1.3(ti)]TJ 11.9629 0 TD .0203 Tc [(tumor)-383.9(e).8(fcacy)-384(a)-5(g)1.9(ainst)-384.1(G)1.1(SH-)]TJ -11.9629 -1.1116 TD .0201 Tc [(O)-4.9(E).5(t)-476.5(p)1.7(retreate)-5.2(d)-476.3(U87)-476.3(c)-5.2(ells)-476.1(tha)-5.2(n)-476.3(nontre)-5.2(a).6(ted)-482.1(cells)-476.1(as)-476.1(w)-4.9(e).6(ll)]TJ 0 -1.1174 TD .0187 Tc [(a)-6.6(s)-356.6(pref)-5.4(era)-6.6(b).3(le)-357.9(acc)-6.6(umul)-5.6(atio)-5.4(n)-351(i)-5.6(n)-351(s)-5.2(ple)-6.6(e)-.8(n)-356.8(a)-.8(nd)-356.8(liv)-5.4(er)-356.7(fol)-5.6(l).2(ow)-6.3(ing)]TJ 0 -1.1116 TD .0189 Tc [(2)-5.2(4)-166.5(h)-350.8(i).4(.v.)-347.4(i)-5.4(njec)-6.4(tio)-5.2(n.)-347.4(Re)-6.4(duct)-5.4(i).4(on)-350.8(an)-5.2(d)-345.1(p).5(H)-351.7(d).5(u)-5.2(a)-.6(l-)-5.2(sen)-5.2(s).7(it)-5.4(ive)-352(S).7(CL)]TJ T* .0204 Tc [(m)-5(i)1.9(celles)-401(w)1.2(ere)-396.6(d)2(e)-4.9(v)2(eloped)]TJ /F6 1 Tf 11.0471 0 TD .019 Tc (via)Tj /F5 1 Tf 1.6876 0 TD .0201 Tc 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[(c)-6.6(ont)-5.6(rol)-5.6(.)-687.4(Fur)-5.4(t).2(her)-5.4(m)-.9(or)-5.4(e,)-687.4(dru)-5.4(g).3(-l)-5.6(oad)-5.4(e)-.8(d)-685.1(d)-5.4(ual-)-5.4(sen)-5.4(s).5(it)-5.6(ive)-692(S).5(CL)]TJ 0 -1.1116 TD [(m)-6.7(i).2(cel)-5.6(les)-287.5(c)-6.6(ould)-287.7(e)-6.6(fc)-6.6(i).2(ent)-5.6(l).2(y)-287.7(t).2(r)-5.4(a)-.8(ns)-5.2(port)-287.8(C)-6.5(PT)-288.9(or)-287.6(DO)-6.3(X)-288.5(i).2(nto)-287.7(c)-6.6(ell)]TJ T* [(n)-5.4(u).3(cl)-5.6(ei,)-284.2(r).4(es)-5.2(ult)-5.6(i).2(ng)-281.9(in)-281.9(e)-6.6(ffe)-6.6(ctiv)-5.4(e)-283.1(cell)-282(a)-6.6(popt)-5.6(osi)-5.6(s).5(.)]TJ 1.0137 -1.1174 TD .0121 Tc [(In)-392.2(con)5.2(t)-.6(r)5.3(a)-1.7(s)5.4(t)-398.1(to)-392.2(carbo)5.2(di)5.1(imid)5.2(e)-399.1(c)4.1(hemis)5.4(t)-.6(r)5.3(y)-397.9(th)5.2(at)-392.3(requi)5.1(res)-397.7(t)-.6(h)5.2(e)]TJ -1.0137 -1.1116 TD .0124 Tc [(use)-439.1(o)5.5(f)-437.9(a)-439.1(cr)5.6(os)5.7(s-l)5.4(i)-.3(n)5.5(k)-.2(er)5.6(,)-440.3(l)5.4(ip)5.5(oy)5.5(l)-438.1(a)-1.4(nd)-432.2(thi)5.4(o)-.2(l)5.4(-fu)5.5(ncti)5.4(on)5.5(ali)5.4(z)-1.4(ed)-437.9(mi)5.4(-)]TJ T* .0127 Tc [(cel)5.7(les)-316.5(a)4.7(re)-312.1(pr)5.9(on)5.8(e)-317.9(t)5.7(o)-316.7(a)4.7(ut)5.7(o-)5.9(cro)5.8(s).3(s)6(-).1(li)5.7(nk)5.8(in)5.8(g.)-313.3(Xu)]TJ /F6 1 Tf 17.6132 0 TD .0089 Tc [(et)-320.6(al.)]TJ /F5 1 Tf 2.4421 0 TD .0117 Tc [(f)4.9(oun)4.8(d)-317.7(t)4.7(hat)]TJ -20.0553 -1.1116 TD .0131 Tc [(SCL)-530.6(m)5(ic)5.1(ell)6.1(e)-.7(s)-529.2(b).5(a)5.1(s).7(ed)-529.4(on)-529.4(PE)5(G-)]TJ /F6 1 Tf 13.0515 0 TD 0 Tc (b)Tj /F5 1 Tf .5126 0 TD .0122 Tc [(-)5.4(P)-.3(CL)-531.5(di)5.2(bl)5.2(ock)-536.1(c)4.2(opo)5.3(ly)5.3(mer)]TJ -13.5641 -1.1174 TD .007 Tc 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[(cells)-583.9(\(11,)-576.9(86\).)-582.7(The)-575.9(resulting)-581.4(SCL)-581.3(polymersomes,)-585.6(while)]TJ T* [(showing)-405.9(remarkable)-408.6(stability)-403.2(against)-407.5(dilution,)-404.4(organic)-401.8(sol-)]TJ 0 -1.1174 TD [(vent,)-504.5(high)-499.9(salt)-501(conditions,)-499.6(and)-505.6(change)-499.7(of)-503.3(temperature)-502(in)]TJ 0 -1.1116 TD [(water,)-340.5(were)-335.9(otherwise)-341.4(completely)-338.7(dissociated)-338.1(in)-336.4(0.5)-166.9(h)-335.2(upon)]TJ T* [(incubation)-313.2(with)-305(10)-169.2(m)]TJ /F6 1 Tf 8.5877 0 TD (M)Tj /F5 1 Tf 1.1404 0 TD [(DTT)-306.1(at)-308.8(pH)-308.3(7.4)-305.1(and)-309.7(37)]TJ /F9 1 Tf 9.1291 0 TD ()Tj /F5 1 Tf .3974 0 TD [(C.)-305.1(These)-308.3(re-)]TJ -19.2547 -1.1174 TD [(versible)-339.5(SCL)-339.4(polymersomes)-340.3(with)-339.6(high)-332.8(protein)-337.4(loading)-337.4(ef-)]TJ 0 -1.1116 TD [(ciency)-206.1(showed)-204.3(much)-196.9(faster)-204.6(CC)-200.1(release)-208.1(into)-200.5(cytosol)-199(of)-203.8(MCF-7)]TJ 25.5097 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[(core)-715.1(under)-715.1(reductive)-722.1(environments)-719.5(results)-717.2(in)-716.5(swelling)]TJ T* [(or)-526.3(dissociation)-534.1(of)-526.3(micelles,)-529.8(facilitating)-535.8(intracellular)-532.2(drug)]TJ 0 -1.1174 TD [(release)-363.6(\(Fig.)-364.9(1D\).)-364.7(Wei)]TJ /F6 1 Tf 9.636 0 TD [(et)-360.6(al.)]TJ /F5 1 Tf 2.4824 0 TD [(constructed)-367(reduction)-363.8(and)-367.3(pH)]TJ -12.1184 -1.1116 TD [(dual-sensitive)-307(DOX-conjugated)-309.8(CCL)-306.1(micelles)-307.5(from)-305.1(PEG-)]TJ /F6 1 Tf 23.4593 0 TD (b)Tj /F5 1 Tf .4953 0 TD (-)Tj -23.9546 -1.1116 TD [(po)20.8(ly)20.7(\(m)19.6(et)19.5(ha)19.7(cr)19.7(yl)14.9(ic)-245.4(ac)18.5(id)20.7(-)]TJ /F6 1 Tf 8.9333 0 TD (g)Tj /F5 1 Tf .4896 0 TD [(-h)20.9(yd)20.8(ra)19.7(zo)19.7(ne)19.7(-D)20(OX)13.3(\))-254.5(d)0(i)20.7(b)0(l)20.7(o)0(c)13.9(k)-254.5(co)19.7(po)20.8(ly)20.7(me)18.4(r)]TJ -9.4229 -1.1174 TD [(containing)-255.6(pendant)-257.8(hydrazide)-255.4(groups)-259.8(\(PEG-)]TJ /F6 1 Tf 17.665 0 TD (b)Tj /F5 1 Tf 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[(and)-741.7(promoted)-748.6(intracellular)-751(DOX)-748.9(release)-749.5(inside)-745.1(GSH-)]TJ 0 -1.1174 TD [(pretreated)-361.4(HeLa)-360.1(cells,)-356.9(resulting)-362.6(in)-353.7(enhanced)-364.8(cell)-358.3(inhibition)]TJ 0 -1.1116 TD [(efcacy.)-320.9(Reduction)-324.6(and)-321.2(pH)-325.6(dual-sensitive)-324.3(DOX-conjugated)]TJ T* [(CCL)-524.9(micelles)-532.1(with)-523.9(an)-527.5(average)-530.7(size)-525(of)-526.3(60)-169.2(nm)-521.8(were)-531.7(pre-)]TJ 0 -1.1174 TD [(pared)-307.3(from)-310.8(p)-24.1(o)-24.1(l)-24.3(y)-18.4(\()]TJ /F6 1 Tf 7.0211 0 TD (N)Tj /F5 1 Tf .6912 0 TD .0242 Tc [(-\(2-hy)5.8(droxyprop)5.8(yl\)met)5.7(hacrylamide\)-)]TJ /F6 1 Tf 15.724 0 TD 0 Tc (b)Tj /F5 1 Tf .5184 0 TD (-)Tj -23.9546 -1.1116 TD [(P)-24(P)-24(D)-19.2(S)-24(E)-25.3(M)-25(A)-468.5(\(PHPMA-)]TJ /F6 1 Tf 9.2904 0 TD (b)Tj /F5 1 Tf .5011 0 TD [(-PPDSEMA\))-451(block)-444.5(copolymers)-446.5(by)]TJ ET q 420.92 0 0 158.74 94.507 573.505 cm /Im5 Do Q BT /F7 1 Tf 9.845 0 0 9.845 59.7543 556.7242 Tm [(FIG.)-284.9(4.)-1000.6(SCL)-286.8(PEG-)]TJ /F4 1 Tf 8.6839 0 TD (b)Tj /F7 1 Tf .4952 0 TD (-Cys)Tj 7.3837 0 0 6.5625 169.2283 555.0802 Tm (4)Tj 9.845 0 0 9.845 172.9133 556.7242 Tm (-)Tj /F4 1 Tf .334 0 TD (b)Tj /F7 1 Tf .501 0 TD [(-PDLLA)-287.2(micelles)-283.4(for)-286.3(enhanced)-287.1(tumor-targeting)-284.1(delivery)-288(of)-284.1(DOX.)-279.8(\(A\))]TJ /F5 1 Tf 30.0423 0 TD [(Fluorescent)-285.1(image)]TJ -42.3714 -1.0135 TD [(of)-284.2(tissue)-277.8(distribution)-283.2(of)-278.4(Cy5.5-labeled)-285(SA)-279(and)-280.6(DS)-279(micelles)-283.6(at)-285.5(1)-277.4(day)-280.5(after)-283.9(injection.)]TJ /F7 1 Tf 33.7796 0 TD (\(B\))Tj /F5 1 Tf 1.6124 0 TD [(Relative)-283.6(tumor)-282.7(volume)-279.1(\(the)-281.7(ratio)-282.9(of)]TJ -35.392 -1.0077 TD [(tumor)-397.9(volume)-400(to)-399.5(initial)-394.8(size)-403.7(before)-394.1(treatment\))-400.9(for)-400.3(M109)-396.4(tumor)-397.9(as)-400.3(a)-393.7(function)-401(of)-399.3(time)-398.2(after)-399.1(intravenously)-395.6(injected)-403.5(DOX)]TJ 0 -1.0135 TD [(formulations)-279.5(\(2)-163.2(mg/kg\))-272.2(at)-274(day)-274.8(0)-271.6(and)-269(4)-271.6(\()]TJ /F6 1 Tf 15.8821 0 TD (n)Tj /F9 1 Tf .668 0 TD (=)Tj /F5 1 Tf .7198 0 TD [(68\).)-272.2(*)]TJ /F6 1 Tf 2.8562 0 TD (p)Tj /F9 1 Tf .6622 0 TD (<)Tj /F5 1 Tf .7198 0 TD [(0.1;)-271.4(**)]TJ /F6 1 Tf 2.8044 0 TD (p)Tj /F9 1 Tf .668 0 TD (<)Tj /F5 1 Tf .7198 0 TD [(0.005.)-269.8(To)-273.8(see)-270(this)-274.8(illustration)-273.1(in)-272.8(color,)-274.6(the)-275(reader)-274.3(is)-272.6(referred)]TJ -25.7004 -1.0135 TD [(to)-336.2(the)-332.6(web)-339(version)-330.6(of)-336(this)-332.4(article)-339.2(at)-331.6(www.liebertpub.com/ars)]TJ /F3 1 Tf 8.9663 0 0 8.9663 59.7543 749.7069 Tm 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[(d)-5.5(i).2(ox)-5.5(a-)-5.4(1,8)-5.5(-oc)-6.6(ta)-6.6(ne)-6.6(dit)-5.6(h).3(i)-5.6(o).3(l)-644.9(t).2(h)-5.5(r).3(o)-5.5(u).3(g)-5.5(h)-639(d)-5.5(i).2(s)-5.3(u).3(l)-5.6().5(de)-645.9(e)-6.6(x)-11.2(c)-6.6(h)-5.5(a)-6.6(n)-11.2(g)-5.5(e)-651.7(r)-5.4(e)-6.6(a)-12.4(c)-6.6(t)-5.6(i)-5.6(o)-11.2(n)]TJ 0 -1.1174 TD -.0217 Tc [(\(2)-5.5(4\).)-255.5(T)-6.7(hes)-5.3(e)-254.3(CC)-6.5(L)-254.4(m)-1(ic)-6.7(ell)-5.6(e)-.9(s)-253(e)-6.7(xhi)-5.6(bit)-5.6(e)-.9(d)-253.2(h)-5.5(igh)-258.9(s).4(ta)-6.7(bil)-5.6(ity)-258.9(in)-258.9(ser)-5.5(u).2(m)-254.4(a)-.9(n)-5.5(d)]TJ 0 -1.1116 TD -.0215 Tc [(we)-6.5(re)-432.7(ex)-5.3(plo)-5.3(r).5(ed)-431.5(f)-5.3(o).4(r)-431.5(c)-6.5(ont)-5.4(rol)-5.4(l).3(ed)-431.5(d)-5.3(e)-.7(li)-5.4(very)-437.3(of)-431.5(va)-6.5(cci)-5.4(nes)-5.1(,)-428.1(i)-5.4(n).4(cl)-5.4(udin)-5.3(g)]TJ T* [(ov)-5.4(alb)-5.4(u).3(min)-264.6(a)-.8(nd)-264.6(immu)-5.4(nos)-5.2(tim)-6.6(ula)-6.6(t).2(or)-5.4(y)-258.8(C)-.7(p)-5.4(G)-.5(-DN)-6.3(A)-.5(.)]TJ 1.0137 -1.1174 TD 0 Tc (Wei)Tj /F6 1 Tf 1.9698 0 TD [(et)-291.5(al.)]TJ /F5 1 Tf 2.3442 0 TD [(reported)-293.4(that)-293.8(reduction-sensitiv)-12(e)-290.2(CCL)-294.5(micelles)]TJ -5.3277 -1.1116 TD [(based)-497.2(on)-497.5(lipoic)-497.7(acid)-496.4(\(LA\)-functionalized)-506.1(PEG-)]TJ /F6 1 Tf 20.0323 0 TD (b)Tj /F5 1 Tf .5011 0 TD (-PHPMA)Tj -20.5333 -1.1116 TD (\(PEG-)Tj /F6 1 Tf 2.5515 0 TD (b)Tj /F5 1 Tf .5011 0 TD [(-PHPMA-LA\))-637.4(conjugates,)-634.3(although)-626.5(highly)-634.7(stable)]TJ -3.0526 -1.1116 TD [(under)-513.5(extensive)-514.6(dilution)-516.2(and)-511.3(concentrated)-520.4(salt)-512.5(condition,)]TJ 0 -1.1174 TD [(swelled)-224.1(to)-215.4(over)-224.4(800)-164.6(nm)-216.5(in)-221.2(response)-223.8(to)-215.4(10)-169.2(m)]TJ /F6 1 Tf 17.1178 0 TD (M)Tj /F5 1 Tf 1.0483 0 TD [(DTT)-219.7(likely)-221.3(due)]TJ -18.1661 -1.1116 TD [(to)-457.3(the)-459.6(increased)-458(hydrophilic)-7.9(ity)-452.8(of)-457.2(micellar)-463.1(core)-461.7(upon)-453.7(de-)]TJ T* [(cross-linking)-188.2(\(81\).)-186.3(These)-187.4(DOX-loaded)-188.9(CCL)-185.1(micelles)-186.5(induced)]TJ 0 -1.1174 TD [(pronounced)-468.3(antitumor)-461.9(effect)-470.9(following)-466.2(48)-163.5(h)-461.9(incubation)-468.8(in)]TJ 0 -1.1116 TD [(HeLa)-331.3(and)-332.8(HepG2)-331(cells)-330.4(with)-328.1(IC)]TJ 7.3823 0 0 6.5614 188.3338 515.2817 Tm (50)Tj 9.843 0 0 9.843 198.9921 516.9258 Tm [(values)-331.4(of)-324.7(6.7)-333.9(and)-327(12.8)]TJ /F10 1 Tf 9.325 0 TD (l)Tj /F5 1 Tf .5529 0 TD (g)Tj -23.7933 -1.1116 TD [(DOX/ml,)-440.4(respectivel)-11.2(y.)-436.5(With)-438.9(a)-440(similar)-442.2(strategy,)-440.8(reduction-)]TJ 0 -1.1174 TD [(sensitive)-375.1(CCL)-369.4(micelles)-376.6(demonstrating)-375.1(accelerated)-377.6(intracel-)]TJ 0 -1.1116 TD [(lular)-461.9(drug)-453.6(release)-461.5(and)-459.5(enhanced)-462.7(cell)-456.2(inhibition)-460.9(were)-456.8(also)]TJ T* [(obtained)-293.6(from)-287.8(starch-)]TJ /F6 1 Tf 8.7144 0 TD (g)Tj /F5 1 Tf .5011 0 TD [(-PEG/LA)-288.2(copolymers)-296.7(\(94\).)-284.2(Wu)]TJ /F6 1 Tf 13.0285 0 TD [(et)-291.5(al.)]TJ /F5 1 Tf -22.244 -1.1174 TD [(developed)-474.3(reduction)-479(and)-471(pH)-469.6(dual-sensiti)-9.9(ve)-469.9(CCL)-473.1(micelles)]TJ 0 -1.1116 TD [(from)-287.8(LA-)-287.6(and)]TJ /F6 1 Tf 5.9152 0 TD (cis)Tj /F5 1 Tf 1.1174 0 TD [(-1,2-cyclohexanedicarboxylic)-296.4(acid)-289.1(\(CCA\)-)]TJ -7.0326 -1.1116 TD [(decorated)-412.1(PEG-)]TJ /F6 1 Tf 6.5315 0 TD (b)Tj /F5 1 Tf .5011 0 TD [(-PLys)-403.7(\(PEG-)]TJ /F6 1 Tf 5.345 0 TD (b)Tj /F5 1 Tf .4953 0 TD [(-PLys-CCA/LA\))-411.9(copolymer)]TJ -12.8729 -1.1116 TD [(\(Fig.)-468.5(5\))-468.7(\(84\).)-468.5(The)-466.4(resulting)-472(robust)-467.3(CCL)-467.3(micelles)-474.5(quickly)]TJ 0 -1.1174 TD [(dissociated)-297.8(into)-292.6(unimers)-298(under)-294.6(a)-290.2(reductive)-295.9(environmen)-8.9(t)-289.2(and)]TJ 0 -1.1116 TD [(released)-301.4(DOX)-299.7(rapidly)-297.1(in)-301.8(response)-298.7(to)-296.1(10)-169.2(m)]TJ /F6 1 Tf 17.0833 0 TD (M)Tj /F5 1 Tf 1.1289 0 TD [(GSH)-298.6(at)-297.2(pH)-302.6(7.4)]TJ -18.2122 -1.1116 TD [(and)-401.9(5.0)-397.3(with)-397.2(86.0%)-400.6(and)-396.1(96.7%)-400.6(of)-393.8(release)-403.9(in)-399.7(24)-163.5(h,)-401.9(respec-)]TJ 0 -1.1174 TD [(tively.)-524.2(Cell)-525.2(experiments)-529.5(revealed)-526.2(that)-524.2(DOX-loaded)-522.9(CCL)]TJ 0 -1.1116 TD (PEG-)Tj /F6 1 Tf 2.2175 0 TD (b)Tj /F5 1 Tf .5011 0 TD [(-PLys-CCA/LA)-278.3(micelles)-278.7(efciently)-279.6(transported)-273.6(DOX)]TJ -2.7186 -1.1116 TD [(into)-206.2(the)-206.2(cell)-202.8(nuclei)-210.8(leading)-206.1(to)-203.9(pronounced)-203.4(cytotoxicit)-9.3(y)-202.7(effects)]TJ 0 -1.1174 TD [(to)-278.8(HeLa)-285.3(and)-280.9(HepG2)-284.9(cells.)]TJ 26.5177 37.8585 TD [(Ab)14.2(du)15.1(ll)14.8(ah)-372(Al)]TJ /F6 1 Tf 5.4256 0 TD [(et)-372.1(al)14.9(.)]TJ /F5 1 Tf 2.4939 0 TD [(fo)15.1(un)15.1(d)-381.2(t)0(h)20.7(a)0(t)-372.1(P)0(T)14(X)0(-)14.2(l)0(o)14.9(a)0(d)13.9(e)0(d)-372(C)0(C)13(L)-376.7(mi)13.7(ce)12.8(ll)14.8(es)]TJ -8.9333 -1.1174 TD [(ba)13.9(se)14.1(d)-208.4(o)0(n)-192.3(t)0(h)15(i)0(o)15(l)0(a)13.8(t)0(e)13.8(d)-202.7(Pl)15.1(ur)15.1(on)15.1(ic)-199.3(F1)15.2(27)-198(be)13.9(ar)19.7(in)14.9(g)-208.4(p)0(e)13.9(n)0(d)20.8(a)0(n)13.9(t)-208.6(th)15(io)20.7(l)-208.6(g)0(r)15.1(o)0(u)15.1(p)0(s)]TJ 0 -1.1116 TD [(in)-434.3(th)15(e)-440(P)0(P)15.4(O)-445.5(bl)14.9(oc)13.9(k)-438.8(d)0(i)14.9(s)0(p)15.3(l)0(a)13.8(y)0(e)19.7(d)-444.6(a)-440(c)0(o)13.9(m)0(p)13.8(a)0(r)14(a)0(b)19.7(l)0(e)-435.5(c)0(y)13.9(t)0(o)15(t)0(o)14.9(x)0(i)14.9(c)-440(ef)14(fe)14(ct)]TJ T* [(to)-336.4(fr)15.1(ee)-332.8(PT)14(X,)-333.7(wi)14.1(th)-330.6(a)-342.1(c)0(e)12.8(l)0(l)-330.8(v)0(i)14.9(a)0(b)13.9(i)0(l)14.8(i)0(t)14.8(y)-340.9(of)-330.5(39)15.1(%)-342(i)0(n)-336.4(A)0(5)14.2(4)0(9)-330.5(c)0(e)12.8(l)0(l)14.8(s)-340.7(fo)15.1(l-)]TJ T* [(lo)15(wi)14.1(ng)-226.8(24)-152(h)-231.5(i)0(n)15(c)0(u)13.9(b)0(a)19.7(t)0(i)14.8(o)0(n)-226.8(a)0(t)-222.4(a)-238.4(PT)19.8(X)-238.1(d)0(o)20.8(s)0(a)14.1(g)0(e)-228(o)0(f)-226.8(1)0(.)18.5(5)]TJ /F10 1 Tf 18.4195 0 TD (l)Tj /F5 1 Tf .5472 0 TD [(g/)14.9(ml)-222.4(\(1)15.1(\).)-223.4(Ya)13(n)]TJ /F6 1 Tf -18.9667 -1.1174 TD [(et)-331.8(al)14.9(.)]TJ /F5 1 Tf 2.4133 0 TD [(ob)15.1(ta)13.8(in)14.9(ed)-331.7(re)14(du)15.1(ct)13.8(io)20.7(n-)15.1(se)14.1(ns)15.3(it)14.8(iv)15(e)-342.1(C)0(C)18.8(L)-342.1(mi)19.5(ce)12.7(ll)14.8(es)-331.5(fr)15.1(om)-331.7(th)14.9(io)14.9(l-)]TJ -2.4133 -1.1116 TD [(co)13.9(nt)14.9(ai)13.8(ni)14.9(ng)-307.5(PE)14(G-)]TJ /F6 1 Tf 6.6755 0 TD (b)Tj /F5 1 Tf .4896 0 TD [(-p)15.1(ol)15(y\()15.1(LA)13(-)]TJ /F6 1 Tf 4.0433 0 TD (co)Tj /F5 1 Tf .9331 0 TD [(-\()15.2(2-)15.1(me)18.4(rc)14(ap)13.9(to)14.9(et)13.8(hy)15.1(l-)15(5-)15.1(me)18.5(th)15(yl)14.9(-2)15.1(-)]TJ -12.1415 -1.1116 TD [(ox)15.1(o-)15.1(1,)12.8(3-)15.1(di)15(ox)20.8(an)13.9(e-)14(5-)15.1(ca)12.8(rb)15.1(ox)15.1(yl)14.9(at)19.5(e\))14(\))-790.1(c)0(o)13.9(p)0(o)15.1(l)0(y)14.9(m)0(e)12.7(r)-790.1(th)20.7(ro)15.1(ug)15.1(h)-790.2(s)0(e)14.1(l)0(f)15(-)]TJ 0 -1.1174 TD [(as)14.1(se)14.1(mb)13.9(ly)-417(in)-411.3(aq)13.9(ue)13.9(ou)15.1(s)-421.4(s)0(o)15.3(l)0(u)15(t)0(i)14.8(o)0(n)-411.1(a)0(n)13.9(d)-421.6(ox)15.1(id)14.9(at)13.8(io)14.9(n)-421.6(o)0(f)-411.1(t)0(h)15(i)0(o)14.9(l)0(s)-416.8(\()0(8)15.1(8)0(\))15.1(.)]TJ 0 -1.1116 TD [(Th)13.9(es)14.1(e)-319(D)0(O)19.1(X)0(-)14.2(l)0(o)15(a)0(d)13.9(e)0(d)-308.6(C)0(C)13(L)-313.3(mi)13.7(ce)18.5(ll)14.8(es)-308.4(ex)13.9(hi)14.9(bi)14.9(te)13.8(d)-312.1(G)0(S)14.4(H)0(-)14.2(d)0(e)13.9(p)0(e)19.7(n)0(d)15.1(e)0(n)13.9(t)]TJ T* [(dr)15.1(ug)-457.2(re)14(le)13.8(as)14.1(e)-463(a)0(n)13.9(d)-467.6(ce)12.8(ll)-451.7(pr)15.1(ol)14.9(if)15(er)14(at)13.8(io)15(n)-461.9(i)0(n)15(h)0(i)14.9(b)0(i)14.9(t)0(i)14.8(o)0(n)15.1(,)-464.2(wh)14.2(er)13.9(ei)19.6(n)-467.6(c)0(e)12.8(l)0(l)]TJ 0 -1.1174 TD [(vi)14.9(ab)13.9(il)14.8(it)14.8(y)-196.9(o)0(f)-186.5(G)0(S)20.1(H)0(-)14.2(p)0(r)15.1(e)0(t)13.8(r)0(e)14(a)0(t)13.8(e)0(d)-187.7(M)0(C)13.1(F)0(-)21(7)-196.9(ce)12.8(ll)14.8(s)-191(d)0(e)13.9(c)0(r)14(e)0(a)12.8(s)0(e)14.1(d)-191.2(fr)15.1(om)-187.7(mo)13.9(re)]TJ 0 -1.1116 TD [(th)15(an)-176.2(60)15.1(%)-180.7(t)0(o)-169.4(l)0(e)13.8(s)0(s)-174.6(t)0(h)20.7(a)0(n)-176.2(3)0(0)15.1(%)-180.7(up)15.1(on)-169.2(in)14.9(cr)14(ea)12.8(si)15.1(ng)-169.2(GS)14.4(H)-180.5(c)0(o)13.9(n)0(c)13.9(e)0(n)13.9(t)0(r)20.7(a)0(t)13.8(i)0(o)15(n)]TJ T* [(fr)15.1(om)-297.2(5)-300.6(t)0(o)-290.3(2)0(0)-152(m)]TJ /F6 1 Tf 6.0304 0 TD (M)Tj /F5 1 Tf .8236 0 TD .3029 Tc [(.L)302.9(i)]TJ /F6 1 Tf 1.7394 0 TD 0 Tc [(et)-291.5(al)14.9(.)]TJ /F5 1 Tf 2.3384 0 TD [(de)13.9(sc)14.1(ri)15(be)13.9(d)-300.6(t)0(h)15(a)0(t)-291.5(r)0(e)14(d)0(u)15.1(c)0(t)13.8(i)0(o)15(n)0(-)20.9(s)0(e)14.1(n)0(s)15.3(i)0(t)14.8(i)0(v)15(e)]TJ -10.9319 -1.1116 TD [(CC)13(L)-232.7(m)0(i)13.7(c)0(e)18.5(l)0(l)14.8(e)0(s)-227.8(b)0(a)19.7(s)0(e)14.1(d)-231.5(on)-221.1(th)15(io)14.9(la)13.8(te)13.8(d)-231.5(t)0(e)19.5(l)0(o)15(d)0(e)13.9(n)0(d)15.1(r)0(i)15(m)0(e)12.7(r)0(s)-220.8(c)0(o)13.9(m)0(p)13.9(o)0(s)15.3(e)0(d)-222.2(o)0(f)]TJ 0 -1.1174 TD [(a)-273(l)0(i)14.8(n)0(e)13.9(a)0(r)-262.5(P)0(E)14(G)-272.7(an)13.9(d)-271.8(a)-267.2(Cy)14(s-)15.3(co)13.9(nt)14.9(ai)13.8(ni)14.9(ng)-261.4(de)13.9(nd)15.1(ri)15(ti)20.6(c)-273(c)0(l)13.8(u)0(s)15.3(t)0(e)13.8(r)-271.8(of)-261.4(ch)13.9(ol)14.9(ic)]TJ 0 -1.1116 TD [(ac)12.8(id)15(s)-271.6(\()0(C)14.1(A)0(s)14.4(\))0(,)-263.7(P)0(E)14(G)0(-)]TJ /F6 1 Tf 7.4127 0 TD (b)Tj /F5 1 Tf .4896 0 TD [(-C)14.1(ys)]TJ 7.3823 0 0 6.5614 409.0959 548.1636 Tm (4)Tj 9.843 0 0 9.843 412.7243 549.8077 Tm [(-L)13.9(ys)]TJ 7.3823 0 0 6.5614 430.4692 548.1636 Tm (8)Tj 9.843 0 0 9.843 434.0408 549.8077 Tm [(-C)14.1(A)]TJ 7.3823 0 0 6.5614 450.7653 548.1636 Tm (8)Tj 9.843 0 0 9.843 454.3936 549.8077 Tm [(,)-268.4(h)0(a)13.9(d)-271.8(su)15.3(pe)19.7(ri)15(or)-267.1(PT)19.8(X-)14.2(lo)14.9(ad)13.9(-)]TJ -14.3589 -1.1116 TD [(in)15(g)-381.2(c)0(a)12.8(p)0(a)13.9(c)0(i)13.8(t)0(y)20.7(,)-383.6(en)13.9(ha)19.7(nc)13.9(ed)-372(mi)13.7(ce)12.8(ll)14.8(ar)-372(st)15.1(ab)13.9(il)14.8(it)14.8(y,)-367.4(pr)15.1(ol)14.9(on)15.1(ge)13.9(d)]TJ /F6 1 Tf 21.4895 0 TD [(in)-370.9(vi)13.8(vo)]TJ /F5 1 Tf -21.4895 -1.1174 TD [(ci)13.8(rc)14(ul)14.9(at)13.8(io)15(n)-346.7(t)0(i)14.8(m)0(e)12.7(,)-349(an)13.9(d)-352.4(p)0(r)20.9(e)0(f)14(e)0(r)14(e)0(n)13.9(t)0(i)14.8(a)0(l)-343.3(a)0(c)12.8(c)0(u)13.9(m)0(u)19.6(l)0(a)13.8(t)0(i)14.8(o)0(n)-342(a)0(t)-343.3(t)0(h)14.9(e)-347.8(tu)14.9(mo)13.9(r)]TJ 0 -1.1116 TD 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[(du)15.1(ct)13.8(iv)15(e)-232.6(e)0(n)13.9(v)0(i)14.9(r)0(o)15.1(n)0(m)13.9(e)0(n)19.7(t)0(.)-223.5(T)0(h)13.9(i)0(s)-226.8(C)0(C)13(L)-232.7(mi)19.5(ce)12.8(ll)14.8(ar)-228(PT)19.8(X)-232.4(e)0(x)13.9(h)0(i)14.9(b)0(i)14.9(t)0(e)13.8(d)-231.5(mo)13.9(re)]TJ T* [(ef)14(fe)14(ct)13.8(iv)15(e)-198.1(t)0(u)15(m)0(o)13.9(r)-196.9(gr)15.1(ow)14.2(th)-186.6(in)14.9(hi)14.9(bi)14.9(ti)14.8(on)-186.5(an)13.9(d)-196.9(l)0(o)15(n)0(g)15.1(e)0(r)-187.6(s)0(u)15.3(r)0(v)15.1(i)0(v)15(a)0(l)-193.6(t)0(i)20.6(m)0(e)-194.7(a)0(t)-187.8(a)]TJ 0 -1.1174 TD [(do)15.1(se)-256.6(of)-249.8(10)-152(mg)-256.9(PT)19.8(X/)14.1(kg)-255.6(th)15(an)-251(th)15(e)-261.4(N)0(C)13.2(L)-261.5(co)13.9(un)20.8(te)13.8(rp)15.1(ar)14(ts)-255.6(an)13.9(d)-260.3(T)0(a)18.5(x)0(o)15.1(l)0(.)]TJ 0 -1.1116 TD -.0153 Tc [(I)-15.3(n)-380.3(a)-380.4(p)-15.3(re)-15.3(vi)-15.3(ou)-15.3(s)-374.4(s)-15.3(tu)-15.3(dy)-15.3(,)-376.9(s)-15.3(im)-15.3(il)-15.3(ar)]TJ /F6 1 Tf 11.6288 0 TD 0 Tc [(in)-359.4(vi)13.8(tr)15.1(o)]TJ /F5 1 Tf 3.3752 0 TD [(re)13.9(le)13.8(as)14.1(e)-365.1(p)0(r)15.1(o)0()15.2(l)0(e)-360.6(a)0(n)13.9(d)-369.7(ce)12.8(ll)]TJ -15.004 -1.1116 TD [(cy)13.9(to)15(to)15(xi)14.9(ci)13.8(ty)-192.4(we)13(re)-193.4(ob)15.1(se)14.1(rv)15.1(ed)-193.4(fo)15.1(r)-202.7(v)0(i)14.9(n)0(c)19.7(r)0(i)15(s)0(t)15.1(i)0(n)14.9(e)-203.8(\(V)14.2(CR)13(\)-)15.1(lo)15(ad)19.7(ed)-199.2(CC)18.8(L)]TJ T* [(PE)14(G-)]TJ /F6 1 Tf 2.1887 0 TD (b)Tj /F5 1 Tf .4953 0 TD [(-C)14.1(ys)]TJ 7.3823 0 0 6.5614 357.7322 427.6345 Tm (4)Tj 9.843 0 0 9.843 361.3038 429.2786 Tm [(-L)13.9(ys)]TJ 7.3823 0 0 6.5614 379.0487 427.6345 Tm (8)Tj 9.843 0 0 9.843 382.6771 429.2786 Tm [(-C)14.1(A)]TJ 7.3823 0 0 6.5614 399.3448 427.6345 Tm (8)Tj 9.843 0 0 9.843 405.9778 429.2786 Tm [(mi)19.5(ce)12.8(ll)14.8(es)-285.4(\(3)15.1(0\))15.1(.)-297.2(T)0(h)19.6(e)]TJ /F6 1 Tf 7.6086 0 TD [(in)-284.5(vi)13.8(vo)]TJ /F5 1 Tf 3.0123 0 TD [(st)15.2(ud)15.1(ie)13.8(s)-294.6(u)0(s)15.3(-)]TJ -20.0611 -1.1174 TD [(in)15(g)-375.5(n)0(u)15.1(d)0(e)-360.5(m)0(i)13.7(c)0(e)-367.4(b)0(e)13.9(a)0(r)19.7(i)0(n)15(g)-375.5(no)15.1(n-)15.1(Ho)20(dg)15.1(ki)14.9(n)15.1(s)-375.3(l)0(y)20.7(m)0(p)13.8(h)0(o)15.1(m)0(a)-367.5(x)0(e)19.7(n)0(o)15.1(g)0(r)15.1(a)0(f)14(t)]TJ 0 -1.1116 TD [(sh)15.3(ow)14.2(ed)-366.2(be)13.9(tt)14.8(er)-366.2(to)15(le)13.8(ra)13.9(nc)13.9(e,)-362.8(im)13.7(pr)15.1(ov)15.1(ed)-366.2(ef)14(c)14.1(ac)18.5(y,)-367.4(an)13.9(d)-369.7(a)0(b)13.9(s)0(e)14.1(n)0(c)13.9(e)-376.6(of)]TJ T* [(ac)12.8(ut)14.9(e)-198.1(n)0(e)13.9(u)0(r)15.1(o)0(t)15(o)0(x)20.8(i)0(c)13.8(i)0(t)14.8(y)-196.9(fo)15.1(r)-196.9(V)0(C)13.2(R)0(-)19.8(l)0(o)15(a)0(d)13.9(e)0(d)-187.7(C)0(C)13(L)-198.1(mi)13.7(ce)18.5(ll)14.8(es)-193.2(at)-187.8(a)-198.1(d)0(o)20.8(s)0(e)-193.2(o)0(f)]TJ 0 -1.1174 TD [(2.)12.7(5)-156.6(m)0(g)-377.8(V)0(C)13.2(R)0(/)19.7(k)0(g)15.1(.)-383.6(Re)12.9(du)15.1(ct)13.8(io)15(n-)20.9(se)14.1(ns)15.3(it)14.8(iv)14.9(e)-382.4(C)0(C)13(L)-382.4(pr)15.1(od)15.1(ru)15.1(g)-381.2(m)0(i)13.7(c)0(e)12.8(l)0(l)14.8(e)0(s)]TJ 0 -1.1116 TD [(we)13(re)-366.2(re)14(ad)13.9(il)14.8(y)-369.7(p)0(r)15.1(e)0(p)13.9(a)0(r)14(e)0(d)-366.2(b)0(a)13.9(s)0(e)14.1(d)-369.7(on)-365.1(po)15.1(ly)14.9(\(m)13.9(et)13.8(ha)19.7(cr)14(yl)14.9(oy)15.1(lo)15(xy)15.1(et)13.8(hy)15.1(l-)]TJ T* .0297 Tc [(pho)5.6(sp)5.6(hor)5.6(yl)5.4(ch)5.6(oli)5.4(n)-.2(e\)-)]TJ /F6 1 Tf 8.6511 0 TD 0 Tc (b)Tj /F5 1 Tf .5241 0 TD .0291 Tc [(-p)5(ol)4.8(y\(2)5(-h)5(ydr)5(ox)5(yethy)5(l)-.9(met)4.8(h)-.8(acr)5(y)-.8(late-)]TJ -9.1752 -1.1174 TD 0 Tc [(dihydr)-6.7(olipoic)-262.7(acid-CPT\))-273.6(block)-266(copolymers)-267.9(\(48\),)-267(resulting)-264.7(in)]TJ ET q 1 i 62.022 334.148 m 398.551 334.148 l 398.551 62.532 l 62.022 62.532 l W n q 336.928 0 0 271.616 62.022 62.532 cm /Im6 Do Q Q BT /F7 1 Tf 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[(24.)-500.5(Heffernan)-333.5(M)-334.8(and)-327.9(Murthy)-331.2(N.)-331.2(Disulde-crosslinked)-342.9(polyion)]TJ 1.7505 -1.1223 TD [(micelles)-388.9(for)-389.3(delivery)-388.9(of)-386.9(protein)-384.5(therapeutics.)]TJ /F6 1 Tf 18.9076 0 TD [(Ann)-386.6(Biomed)]TJ -18.9076 -1.1284 TD (Eng)Tj /F5 1 Tf 1.9457 0 TD [(37:)-335.3(19932002,)-330.8(2009.)]TJ -3.6961 -1.1223 TD [(25.)-500.5(Hu)-245.8(X,)-245.8(Li)-245.6(H,)-245.8(Luo)-246.3(S,)-241(Liu)-245.7(T,)-246.1(Jiang)-247.4(Y,)-245.8(and)-248.6(Liu)-245.7(S.)-241(Thiol)-245.4(and)-248.6(pH)]TJ 1.7505 -1.1284 TD [(dual-responsive)-522.8(dynamic)-514.7(covalent)-518.9(shell)-521.3(cross-linked)-518.1(mi-)]TJ 0 -1.1223 TD [(celles)-609.2(for)-615(triggered)-610.9(release)-610.3(of)-612.5(chemotherapeutic)-613.3(drugs.)]TJ /F6 1 Tf 0 -1.1284 TD [(Polym)-337.2(Chem)]TJ /F5 1 Tf 5.5625 0 TD [(4:)-335.2(695706,)-330.5(2013.)]TJ -7.313 -1.1284 TD [(26.)-500.5(Huang)-378.6(H,)-379.9(Zhang)-378.9(X,)-379.9(Yu)-380(J,)-377.5(Zeng)-378.7(J,)-377.5(Chang)-381.8(PR,)-380.1(Xu)-373.9(H,)-379.9(and)]TJ 1.7505 -1.1223 TD [(Huang)-445.7(J.)-444.6(Fabrication)-450.8(and)-449.9(reduction-sensitive)-446.5(behavior)-450.5(of)]TJ 0 -1.1284 TD [(polyion)-384.1(complex)-380.5(nano-micelles)-390.1(based)-386.4(on)-378.4(PEG-conjugated)]TJ 0 -1.1223 TD [(polymer)-287.1(containing)-288.7(disulde)-292.9(bonds)-286.5(as)-290.3(a)-284.9(potential)-294.1(carrier)-288.4(of)]TJ 0 -1.1284 TD [(anti-tumor)-300.9(paclitaxel.)]TJ /F6 1 Tf 9.0086 0 TD [(Colloid)-296.8(Surface)-306.8(B)]TJ /F5 1 Tf 7.5813 0 TD [(110:)-305(5965,)-299.7(2013.)]TJ -18.3404 -1.1223 TD [(27.)-500.5(Huang)-287.1(X,)-288.5(Jiang)-284(X,)-288.5(Yang)-286.9(Q,)-282.4(Chu)-285.8(Y,)-288.5(Zhang)-287.4(G,)-282.4(Yang)-286.9(B,)-285.6(and)]TJ 1.7505 -1.1284 TD [(Zhuo)-691.7(R.)-694.2(Triple-stimuli)-691.1(\(pH/thermo/reduction\))-700.3(sensitive)]TJ 0 -1.1223 TD [(copolymers)-236(for)-236.8(intracellular)-240.1(drug)-234.7(delivery.)]TJ /F6 1 Tf 17.2608 0 TD [(J)-236.1(Mater)-231.6(Chem)]TJ /F5 1 Tf 5.9346 0 TD (1:)Tj -23.1954 -1.1284 TD [(18601868,)-330.8(2013.)]TJ -1.7505 -1.1223 TD [(28.)-500.5(Jia)-436.2(Z,)-435.2(Wong)-431.9(L,)-435.2(Davis)-438.1(TP,)-432.1(and)-437.7(Bulmus)-430.7(V.)-434.8(One-pot)-441.6(con-)]TJ 1.7505 -1.1284 TD [(version)-384.2(of)-380.8(RAFT-generated)-393.9(multifunctional)-381.1(block)-388.6(copoly-)]TJ 0 -1.1223 TD [(mers)-688.9(of)-691.8(HPMA)-695.1(to)-688.9(doxorubicin)-690.1(conjugated)-696(acid-)-687.9(and)]TJ 0 -1.1284 TD [(reductant-sensitive)-670.3(crosslinked)-668.1(micelles.)]TJ /F6 1 Tf 17.7427 0 TD (Biomacromole-)Tj -17.7427 -1.1223 TD (cules)Tj /F5 1 Tf 2.397 0 TD [(9:)-335.2(31063113,)-330.8(2008.)]TJ -4.1475 -1.1284 TD [(29.)-500.5(Jiang)-448.7(X,)-447(Li)-446.8(L,)-441.2(Liu)-447(J,)-444.6(Hennink)-451.5(WE,)-445.7(and)-443.8(Zhuo)-447.7(R.)-450.2(Facile)]TJ 1.7505 -1.1223 TD [(fabrication)-566.1(of)-563.7(thermo-responsive)-561.5(and)-565.8(reduction-sensitive)]TJ 0 -1.1284 TD [(polymeric)-284.9(micelles)-291.3(for)-285.6(anticancer)-285.9(drug)-283.5(delivery.)]TJ /F6 1 Tf 19.8103 0 TD (Macromol)Tj -19.8103 -1.1223 TD (Biosci)Tj /F5 1 Tf 2.8422 0 TD [(12:)-335.3(703711,)-330.5(2012.)]TJ 22.4147 70.8975 TD [(30.)-500.5(Kato)-463.2(K,)-465.3(Chin)-462.2(K,)-459.2(Yoshikawa)-468.9(T,)-459.5(Yamaguchi)-465.9(K,)-459.2(Tsuji)-464.1(Y,)]TJ 1.7505 -1.1223 TD [(Esaki)-395.7(T,)-392.5(Sakai)-389.6(K,)-392.1(Kimura)-392.2(M,)-389.8(Hamaguchi)-398.8(T,)-392.5(Shimada)-389.5(Y,)]TJ 0 -1.1284 TD [(Matsumura)-424.2(Y,)-422.6(and)-425.5(Ikeda)-420.1(R.)-425.8(Phase)-419.8(II)-425.8(study)-420.1(of)-423.5(NK105,)-424.8(a)]TJ 0 -1.1223 TD [(paclitaxel-incorporating)-568.4(micellar)-562.9(nanoparticle,)-562.1(for)-560.1(previ-)]TJ 0 -1.1283 TD [(ously)-414(treated)-411.2(advanced)-414.4(or)-411.3(recurrent)-410.7(gastric)-418.4(cancer.)]TJ /F6 1 Tf 21.5791 0 TD (Invest)Tj 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[(cross-links)-451.9(for)-444.2(delivery)-443.8(of)-441.7(chemotherapeutic)-454.7(agents.)]TJ /F6 1 Tf 22.2439 0 TD (Bio-)Tj -22.2439 -1.1284 TD (macromolecules)Tj /F5 1 Tf 6.8982 0 TD [(11:)-335.3(919926,)-330.5(2010.)]TJ -8.6487 -1.1223 TD [(33.)-500.5(Koo)-276.5(AN,)-271.9(Lee)-273(HJ,)-269.4(Kim)-275.5(SE,)-273.5(Chang)-272(JH,)-269.4(Park)-272.3(C,)-273.4(Kim)-275.5(C,)-267.3(Park)]TJ 1.7505 -1.1284 TD [(JH,)-495.1(and)-492.6(Lee)-492.6(SC.)-489.9(Disulde-cross-linked)-497.9(PEG-poly\(amino)]TJ 0 -1.1223 TD [(acid\)s)-412.7(copolymer)-413.6(micelles)-413.3(for)-413.7(glutathione-mediated)-412.7(intra-)]TJ 0 -1.1284 TD [(cellular)-313.2(drug)-307.9(delivery.)]TJ /F6 1 Tf 9.3196 0 TD [(Chem)-303.9(Commun)-313.8(\(Camb\))]TJ /F5 1 Tf 9.9052 0 TD (65706572,)Tj -19.2248 -1.1223 TD (2008.)Tj -1.7505 -1.1284 TD [(34.)-500.5(Koo)-264.3(AN,)-259.7(Min)-255.3(KH,)-259.7(Lee)-260.8(HJ,)-257.2(Lee)-260.8(S-U,)-263.5(Kim)-257.2(K,)-258(Chan)-259.6(Kwon)-259.9(I,)]TJ 1.7505 -1.1223 TD [(Cho)-328.5(SH,)-322(Jeong)-327.3(SY,)-322(and)-327.9(Lee)-321.8(SC.)-325.2(Tumor)-327.8(accumulation)-327.5(and)]TJ 0 -1.1284 TD [(antitumor)-548.5(efcacy)-547.6(of)-539.3(docetaxel-loaded)-552.7(core-shell-corona)]TJ 0 -1.1223 TD [(micelles)-523.1(with)-519.4(shell-specic)-520.6(redox-responsive)-525.8(cross-links.)]TJ /F6 1 Tf 0 -1.1284 TD (Biomaterials)Tj /F5 1 Tf 5.5137 0 TD [(33:)-335.3(14891499,)-330.8(2012.)]TJ -7.2642 -1.1223 TD .0117 Tc [(3)11.7(5)11.7(.)-488.8(Kup)5.5(pusamy)-330(P)2.6(,)-336(L)3.6(i)-335.5(H)3.9(,)-329.9(I)-3(lang)5.5(ovan)-330(G)-2.2(,)-329.9(C).7(ard)5.5(ounel)-329.4(A)-2.2(J,)-329.9(Zweier)]TJ 1.7505 -1.1284 TD [(JL,)-604.5(Y)3.8(amada)-602.7(K)-2.3(,)-598.4(K)-2.3(rishna)-602.7(MC,)-604.5(a)1.2(n)5.4(d)-604.6(Mitchell)-604(JB.)-598.4(N)-2.3(on)5.4(-)]TJ 0 -1.1223 TD [(invasiv)5.5(e)-352.5(imaging)-348.3(o)-.6(f)-350.6(t)-.1(u)5.5(m)-.2(or)-350.6(red)5.5(o)-.6(x)-354.4(s).2(t)11.7(a)-10.5(t)11.7(u)-6.3(s)-353.5(a)1.3(nd)-348.3(its)-353.5(m)11.7(o)-6.5(dica-)]TJ 0 -1.1284 TD [(tion)-256.8(b)-.6(y)-256.8(t)-.1(i)11.7(s)-5.4(sue)-261(g)5.5(lutath)5.5(ione)-254.9(levels.)]TJ /F6 1 Tf 13.5708 0 TD .0114 Tc [(Cancer)-256.2(Res)]TJ /F5 1 Tf 5.0075 0 TD .0123 Tc [(62:)-255.6(30)6.1(731)6.1(2,)]TJ -18.5783 -1.1223 TD [(2002)6.1(.)]TJ -1.7505 -1.1284 TD 0 Tc [(36.)-500.5(Lackman)-460.3(RL,)-452.3(Jamieson)-458.1(AM,)-452.5(Grifth)-454.2(JM,)-450.1(Geuze)-460.2(H,)-453.1(and)]TJ 1.7505 -1.1223 TD [(Cresswell)-369.2(P.)-356.9(Innate)-364.8(immune)-363.5(recognition)-364.4(triggers)-361.7(secretion)]TJ 0 -1.1284 TD [(of)-441.7(lysosomal)-441.3(enzymes)-445.4(by)-439.4(macrophages.)]TJ /F6 1 Tf 17.151 0 TD (Trafc)Tj /F5 1 Tf 3.1045 0 TD [(8:)-438.9(1179)]TJ -20.2556 -1.1223 TD [(1189,)-336.1(2007.)]TJ -1.7505 -1.1284 TD [(37.)-500.5(Lee)-291.3(S-Y,)-287.9(Kim)-287.7(S,)-289.8(Tyler)-289.1(JY,)-287.7(Park)-290.6(K,)-288.5(and)-285.2(Cheng)-290.3(J-X.)-290.2(Blood-)]TJ 1.7505 -1.1223 TD [(stable,)-623.3(tumor-adaptable)-625.3(disulde)-616.2(bonded)-621.1(mPEG-\(Cys\))]TJ 6.9712 0 0 6.196 545.6125 367.9369 Tm (4)Tj 9.2951 0 0 9.2951 549.0707 369.5243 Tm (-)Tj -23.6406 -1.1284 TD [(PDLLA)-773(micelles)-773.1(for)-767.5(chemotherapy.)]TJ /F6 1 Tf 16.7485 0 TD (Biomaterials)Tj /F5 1 Tf 5.9468 0 TD (34:)Tj -22.6953 -1.1223 TD [(552561,)-336.6(2013.)]TJ -1.7505 -1.1284 TD [(38.)-500.5(Li)-361.5(J,)-353.1(Huo)-355.8(M,)-359.3(Wang)-356.8(J,)-353.1(Zhou)-356.2(J,)-359.2(Mohammad)-355.6(JM,)-358.6(Zhang)-354.5(Y,)]TJ 1.7505 -1.1223 TD [(Zhu)-441.5(Q,)-440.9(Waddad)-446.7(AY,)-442.7(and)-443.8(Zhang)-439.9(Q.)-440.9(Redox-sensitive)-445.4(mi-)]TJ 0 -1.1284 TD [(celles)-542.1(self-assembled)-537.7(from)-535.4(amphiphilic)-537.9(hyaluronic)-535.6(acid-)]TJ 0 -1.1223 TD 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(Biomacromo-)Tj -18.4746 -1.1284 TD (lecules)Tj /F5 1 Tf 3.1289 0 TD [(12:)-329.2(15671577,)-336.9(2011.)]TJ -4.8794 -1.1223 TD [(46.)-500.5(Liu)-300.6(J,)-292.1(Pang)-300.4(Y,)-294.6(Huang)-299.3(W,)-297.3(Zhu)-295.1(Z,)-301(Zhu)-295.1(X,)-294.6(Zhou)-295.2(Y,)-300.7(and)-297.4(Yan)]TJ 1.7505 -1.1284 TD [(D.)-325.1(Redox-responsive)-333.1(polyphosphate)-325.4(nanosized)-329.6(assemblies:)]TJ 0 -1.1223 TD [(a)-339.8(smart)-340.8(drug)-344.5(delivery)-340.1(platform)-343.9(for)-334.4(cancer)-343.3(therapy.)]TJ /F6 1 Tf 21.0302 0 TD (Bioma-)Tj -21.0302 -1.1284 TD (cromolecules)Tj /F5 1 Tf 5.6784 0 TD [(12:)-335.3(24072415,)-330.8(2011.)]TJ -7.4289 -1.1284 TD [(47.)-500.5(Ma)-430.7(N,)-428.7(Li)-434.6(Y,)-428.7(Xu)-428.8(H,)-428.7(Wang)-436.1(Z,)-429.1(and)-425.5(Zhang)-433.8(X.)-428.7(Dual)-432.7(redox)]TJ 1.7505 -1.1223 TD [(responsive)-491.7(assemblies)-491.7(formed)-491.1(from)-486.6(diselenide)-487.2(block)-492.3(co-)]TJ 0 -1.1284 TD (polymers.)Tj /F6 1 Tf 4.3122 0 TD [(J)-333.7(A)0(m)-339.2(Chem)-334.4(Soc)]TJ /F5 1 Tf 6.8982 0 TD [(132:)-335.5(442443,)-330.5(2010.)]TJ -12.9609 -1.1223 TD [(48.)-500.5(McRae)-511.4(Page)-505.9(S,)-509.3(Martorella)-510.3(M,)-505.7(Parelkar)-508.7(S,)-509.3(Kosif)-509.4(I,)-502.7(and)]TJ 1.7505 -1.1284 TD [(Emrick)-551.1(T.)-544.9(Disulde)-550.6(cross-linked)-554.7(phosphorylcholine)-547.3(mi-)]TJ 0 -1.1223 TD [(celles)-255.4(for)-249(triggered)-251.1(release)-250.5(of)-246.6(camptothecin.)]TJ /F6 1 Tf 17.8647 0 TD [(Mol)-246.3(Pharm)]TJ /F5 1 Tf 4.8306 0 TD (10:)Tj -22.6952 -1.1284 TD [(26842692,)-336.9(2013.)]TJ -1.7505 -1.1223 TD [(49.)-500.5(Meng)-260.2(F,)-253.2(Cheng)-253.7(R,)-255.1(Deng)-256.4(C,)-255.1(and)-260.8(Zhong)-252.7(Z.)-252.2(Intracellular)-261.2(drug)]TJ 1.7505 -1.1284 TD [(release)-342(nanosystems.)]TJ /F6 1 Tf 8.8256 0 TD [(Mater)-335.3(Today)]TJ /F5 1 Tf 5.6113 0 TD [(15:)-335.3(436442,)-330.5(2012.)]TJ -16.1874 -1.1223 TD [(50.)-500.5(Meng)-388.3(F,)-381.3(Hennink)-384.4(WE,)-384.8(and)-382.8(Zhong)-386.9(Z.)-380.3(Reduction-sensitive)]TJ 1.7505 -1.1284 TD [(polymers)-499.8(and)-498.7(bioconjugates)-499.8(for)-499.1(biomedical)-499.9(applications.)]TJ /F6 1 Tf 0 -1.1223 TD (Biomaterials)Tj /F5 1 Tf 5.5137 0 TD [(30:)-329.2(21802198,)-336.9(2009.)]TJ -7.2642 -1.1284 TD [(51.)-500.5(Meng)-302.9(F)-308(and)-303.5(Zhong)-301.5(Z.)-301(Polymersomes)-311(spanning)-302.8(from)-303.6(nano-)]TJ 1.7505 -1.1223 TD [(to)-390.1(microscales:)-401.2(advanced)-390(vehicles)-396(for)-389.3(controlled)-394.7(drug)-393.2(de-)]TJ 0 -1.1284 TD [(livery)-378.3(and)-376.7(robust)-379.9(vesicles)-376.8(for)-377.1(virus)-373.6(and)-376.7(cell)-379.9(mimicking.)]TJ /F6 1 Tf 23.5247 0 TD (J)Tj -23.5247 -1.1223 TD [(Phys)-335.1(Chem)-334.4(Lett)]TJ /F5 1 Tf 6.8433 0 TD [(2:)-335.2(15331539,)-330.8(2011.)]TJ -8.5938 -1.1284 TD [(52.)-500.5(Meng)-388.3(F,)-387.4(Zhong)-380.8(Z,)-386.4(and)-388.9(Feijen)-383.1(J.)-389.7(Stimuli-responsive)-385.5(poly-)]TJ 1.7505 -1.1223 TD [(mersomes)-405.7(for)-407.6(programmed)-404(drug)-405.4(delivery.)]TJ /F6 1 Tf 17.7488 0 TD (Biomacromole-)Tj -17.7488 -1.1284 TD (cules)Tj /F5 1 Tf 2.397 0 TD [(10:)-335.3(197209,)-330.5(2009.)]TJ -4.1475 -1.1223 TD [(53.)-500.5(Nam)-505.9(K,)-501.9(Nam)-499.8(HY,)-503.7(Kim)-501.1(P-H,)-501.3(and)-498.7(Kim)-507.2(SW.)-501.6(Paclitaxel-)]TJ 1.7505 -1.1284 TD [(conjugated)-598.5(PEG)-592.3(and)-596.3(arginine-grafted)-600(bioreducible)-594.4(poly)]TJ 0 -1.1223 TD [(\(disulde)-258.8(amine\))-260.7(micelles)-260.8(for)-255.1(co-delivery)-261.7(of)-252.7(drug)-259.1(and)-254.7(gene.)]TJ /F6 1 Tf 0 -1.1284 TD (Biomaterials)Tj /F5 1 Tf 5.5137 0 TD [(33:)-329.2(81228130,)-336.9(2012.)]TJ -7.2642 -1.1223 TD [(54.)-500.5(Peer)-300.9(D,)-300.7(Karp)-301.4(JM,)-303.7(Hong)-301(S,)-295.9(Farokhzad)-305.8(OC,)-299.5(Margalit)-302.2(R,)-303.9(and)]TJ 1.7505 -1.1284 TD [(Langer)-281.9(R.)-279.5(Nanocarriers)-281.8(as)-278.1(an)-279(emerging)-279.3(platform)-276.8(for)-279.5(cancer)]TJ 0 -1.1223 TD (therapy.)Tj /F6 1 Tf 3.5924 0 TD [(Nat)-340.1(Nanotechnol)]TJ /F5 1 Tf 7.2398 0 TD [(2:)-335.2(751760,)-336.6(2007.)]TJ -12.5827 -1.1284 TD [(55.)-500.5(Ren)-412(T-B,)-418.1(Feng)-410.2(Y,)-410.4(Zhang)-415.5(Z-H,)-414.9(Li)-410.2(L,)-410.8(and)-413.3(Li)-410.3(Y-Y.)-414.6(Shell-)]TJ 1.7505 -1.1223 TD [(sheddable)-677.3(micelles)-681.7(based)-673.1(on)-677.3(star-shaped)-675.2(poly\()]TJ /F10 1 Tf 20.6947 0 TD (e)Tj /F5 1 Tf .3843 0 TD (-capro-)Tj -21.079 -1.1284 TD [(lactone\)-SS-poly\(ethyl)-428.7(glycol\))-415(copolymer)-425.8(for)-413.7(intracellular)]TJ 0 -1.1223 TD [(drug)-338.4(release.)]TJ /F6 1 Tf 5.5442 0 TD [(Soft)-334.9(Matter)]TJ /F5 1 Tf 4.9587 0 TD [(7:)-329.1(23292331,)-336.9(2011.)]TJ -12.2534 -1.1284 TD [(56.)-500.5(Ren)-485.2(T-B,)-485.2(Xia)-487.5(W-J,)-482(Dong)-484(H-Q,)-487.8(and)-480.4(Li)-483.4(Y-Y.)-487.8(Sheddable)]TJ 1.7505 -1.1223 TD [(micelles)-303.5(based)-294.9(on)-293(disulde-linked)-299.3(hybrid)-295.4(PEG-polypeptide)]TJ 0 -1.1284 TD [(copolymer)-602.7(for)-602.8(intracellular)-606(drug)-600.6(delivery.)]TJ /F6 1 Tf 18.7003 0 TD (Polymer)Tj /F5 1 Tf 3.995 0 TD (52:)Tj -22.6952 -1.1284 TD [(35803586,)-336.9(2011.)]TJ -1.7505 -1.1223 TD [(57.)-500.5(Ryu)-310.2(J-H,)-314.6(Roy)-310.2(R,)-310(Ventura)-311.6(J,)-310.4(and)-309.6(Thayumanavan)-312.8(S.)-314.2(Redox-)]TJ 1.7505 -1.1284 TD [(sensitive)-677.1(disassembly)-676.7(of)-673.5(amphiphilic)-672.1(copolymer)-675.9(based)]TJ 0 -1.1223 TD (micelles.)Tj /F6 1 Tf 3.9401 0 TD (Langmuir)Tj /F5 1 Tf 4.2695 0 TD [(26:)-335.3(70867092,)-330.8(2010.)]TJ -9.9601 -1.1284 TD [(58.)-500.5(Samarajeewa)-355.9(S,)-350.8(Shrestha)-354.9(R,)-346.6(Elsabahy)-351.6(M,)-347.1(Karwa)-356.2(A,)-349.4(Li)-349.3(A,)]TJ 1.7505 -1.1223 TD [(Zentay)-486.3(RP,)-483.8(Kostelc)-484.7(JG,)-476.8(Dorshow)-487.4(RB,)-479.6(and)-486.5(Wooley)-478.5(KL.)]TJ /F6 1 Tf 0 -1.1284 TD [(In)-344.2(vitro)]TJ /F5 1 Tf 3.4217 0 TD [(efcacy)-346.3(of)-344.2(paclitaxel-loaded)-356.5(dual-responsive)-345.9(shell)]TJ -3.4217 -1.1223 TD [(cross-linked)-640.1(polymer)-628.7(nanoparticles)-640.5(having)-632.7(orthogonally)]TJ 0 -1.1284 TD [(degradable)-282.3(disulde)-274.6(cross-linked)-274.1(corona)-273.9(and)-279.1(polyester)-272.3(core)]TJ 0 -1.1223 TD (domains.)Tj /F6 1 Tf 3.9828 0 TD [(Mol)-331.7(Pharm)]TJ /F5 1 Tf 4.9953 0 TD [(10:)-335.3(10921099,)-330.8(2013.)]TJ -10.7286 -1.1284 TD [(59.)-500.5(Schafer)-423.7(FQ)-419.5(and)-419.4(Buettner)-424.2(GR.)-415.4(Redox)-424.5(environment)-419.4(of)-417.4(the)]TJ 1.7505 -1.1223 TD [(cell)-416.5(as)-418.4(viewed)-418.9(through)-417.5(the)-412.7(redox)-415.9(state)-415.7(of)-417.4(the)-418.8(glutathione)]TJ 0 -1.1284 TD [(disulde/glutathione)-641.7(couple.)]TJ /F6 1 Tf 12.4485 0 TD [(Free)-644.3(Radic)-634.5(Biol)-635.6(Med)]TJ /F5 1 Tf 10.2467 0 TD (30:)Tj -22.6952 -1.1223 TD [(11911212,)-336.9(2001.)]TJ -1.7505 -1.1284 TD [(60.)-500.5(Sun)-271.7(HL,)-266.1(Guo)-270.4(BN,)-269(Cheng)-272(R,)-267.3(Meng)-272.4(FH,)-267.1(Liu)-270.1(HY,)-271.9(and)-266.9(Zhong)]TJ 1.7505 -1.1223 TD [(ZY.)-375.9(Biodegradable)-378.4(micelles)-382.8(with)-373.1(sheddable)-378.4(poly\(ethylene)]TJ 0 -1.1284 TD [(glycol\))-348(shells)-343.7(for)-346.6(triggered)-342.6(intracellular)-349.8(release)-348.1(of)-344.2(doxoru-)]TJ 0 -1.1223 TD (bicin.)Tj /F6 1 Tf 2.5983 0 TD (Biomaterials)Tj /F5 1 Tf 5.5076 0 TD [(30:)-335.3(63586366,)-330.8(2009.)]TJ 17.1572 70.8975 TD .5308 Tc [(6)530.8(1)530.8(.)30.3(S)521.7(u)518.5(nH)523(L)516.6(,).1(G)516.9(u)524.6(oB)519.8(N)516.9(,).1(C)519.8(h)518.5(e)520.4(n)518.5(gR)519.8(,M)519.2(e)520.4(n)518.5(gF)521.7(H)516.9(,).1(L)522.7(i)519(uH)516.9(Y)523(,).1(a)514.3(n)524.6(d)]TJ 1.7505 -1.1223 TD .0115 Tc [(Zhon)5.3(g)-464.4(Z)-2.7(Y.)-464.3(Reducti)11.5(o)-6.5(n)-.8(-sensitiv)5.3(e)-468.6(d)5.3(egrad)5.3(a)-5(b)5.3(l)-.3(e)-462.5(m)-.4(icellar)-466.7(n)5.3(a-)]TJ 9.2951 0 0 9.2951 327.118 704.2392 Tm [(n)5.3(oparticles)-512.3(a)1.1(s)-512.3(s)0(mart)-512.6(and)-507.1(i)-.3(ntui)11.5(t)-5.9(i)-.3(ve)-511.3(deliv)5.3(ery)-507.1(s)0(ystems)-506.2(for)]TJ T* .0111 Tc [(cancer)-314.6(chemot)11.1(h)-6.9(e).7(rapy.)]TJ /F6 1 Tf 9.3867 0 TD 0 Tc [(E)-14.2(x)-10.4(p)-12.3(e)-10.4(r)-11.5(t)-322.8(O)-13.9(p)-12.3(in)-329.1(D)-13.9(r)-11.5(u)-12.3(g)-323.4(D)-7.8(e)-16.5(li)-17.4(v)]TJ /F5 1 Tf 10.4175 0 TD .0123 Tc [(1)6.1(0)0(:)-310.5(1109)6.1()]TJ -19.8042 -1.1283 TD [(1)6.1(122,)-329.3(20)6.1(13.)]TJ -1.7505 -1.1223 TD 0 Tc [(62.)-500.5(Sun)-247.3(HL,)-247.8(Guo)-252.1(BN,)-250.7(Li)-245.6(XQ,)-253.6(Cheng)-247.6(R,)-249(Meng)-254.1(FH,)-248.8(Liu)-245.7(HY,)-253.6(and)]TJ 1.7505 -1.1284 TD [(Zhong)-325.9(ZY.)-327.1(Shell-sheddable)-326.6(micelles)-334(based)-325.4(on)-323.5(dextran-SS-)]TJ 0 -1.1223 TD (poly\()Tj /F10 1 Tf 2.1103 0 TD (e)Tj /F5 1 Tf .3904 0 TD [(-caprolactone\))-352.1(diblock)-345.6(copolymer)-352.6(for)-346.6(efcient)-347.2(intra-)]TJ -2.5007 -1.1284 TD [(cellular)-599.9(release)-604.2(of)-600.3(doxorubicin.)]TJ /F6 1 Tf 14.1319 0 TD (Biomacromolecules)Tj /F5 1 Tf 8.5572 0 TD (11:)Tj -22.6892 -1.1223 TD [(848854,)-330.5(2010.)]TJ -1.7505 -1.1284 TD [(63.)-500.5(Sun)-351(L,)-349.8(Liu)-355.5(W,)-352.2(and)-352.3(Dong)-355.9(C-M.)-354.5(Bioreducible)-355.2(micelles)-358.4(and)]TJ 1.7505 -1.1223 TD [(hydrogels)-457.7(with)-458.4(tunable)-459.6(properties)-463.8(from)-456.1(multi-armed)-463.4(bio-)]TJ 0 -1.1284 TD [(degradable)-337.2(copolymers.)]TJ /F6 1 Tf 10.0027 0 TD [(Chem)-334.4(Commun)]TJ /F5 1 Tf 6.6055 0 TD [(47:)-335.3(1128211284,)]TJ -16.6082 -1.1284 TD (2011.)Tj -1.7505 -1.1223 TD [(64.)-500.5(Sun)-338.8(P,)-344.7(Zhou)-344(D,)-337.3(and)-346.2(Gan)-341.7(Z.)-343.7(Novel)-347.5(reduction-sensitive)-342.8(mi-)]TJ 1.7505 -1.1284 TD [(celles)-511.6(for)-517.4(triggered)-513.3(intracellular)-520.6(drug)-509.1(release.)]TJ /F6 1 Tf 19.8957 0 TD [(J)-516.7(Control)]TJ -19.8957 -1.1223 TD (Release)Tj /F5 1 Tf 3.4583 0 TD [(155:)-329.4(96103,)-336.4(2011.)]TJ -5.2087 -1.1284 TD .014 Tc [(6)14(5)14(.)-486.5(S)4.9(u)1.7(n)-529(Y).1(,)-535(Y)6.2(an)-529(X,)-535(Y)6.2(u)1.7(an)-535.1(T,)-528.9(Liang)-529(J)2.5(,)-535(F)4.9(an)-529(Y,)-535(G)6.2(u)-535.1(Z,)-528.9(an)7.8(d)]TJ 1.7505 -1.1223 TD .0125 Tc [(Zhang)-481.7(X)-1.4(.)-481.6(D)-1.4(i)12.5(s)-4.6(as)12.5(sem)12.5(b)-5.7(lable)-479.8(m).6(icel)12.5(l)-4.9(e)2.1(s)-486.9(b).2(ased)-481.7(on)-481.7(redu)6.3(ction-)]TJ 0 -1.1284 TD .0104 Tc [(de)-6.1(gradabl)10.4(e)-335.1(amphiphilic)-323.3(gra)-6.1(f)1.8(t)-324.6(c)]TJ 12.8084 0 TD [(opolymers)-324.2(f)-4.2(or)-327.4(intracellul)10.5(a)-11.7(r)]TJ -12.8084 -1.1223 TD .012 Tc [(d)5.8(e)-4.5(l)12(i)-5.4(very)-610.3(o)5.8(f)-612.6(do)5.8(xorubicin)5.8(.)]TJ /F6 1 Tf 11.2836 0 TD [(Bio)5.7(m)-2(ateria)5.7(ls)]TJ /F5 1 Tf 5.9163 0 TD .0123 Tc [(31:)-609.4(7)6.1(124)6.1(7131)6.1(,)]TJ -17.1998 -1.1284 TD [(2)6.1(010.)]TJ -1.7505 -1.1223 TD 0 Tc [(66.)-500.5(Sun)-332.7(Y,)-331.2(Zou)-331.7(W,)-333.9(Bian)-338.3(S,)-332.5(Huang)-335.9(Y,)-331.2(Tan)-335.9(Y,)-331.2(Liang)-335.6(J,)-334.8(Fan)-336.9(Y,)]TJ 1.7505 -1.1284 TD [(and)-248.6(Zhang)-244.7(X.)-251.9(Bioreducible)-251.5(PAA-g-PEG)-250.1(graft)-253(micelles)-248.6(with)]TJ 0 -1.1223 TD [(high)-622.1(doxorubicin)-623(loading)-626.2(for)-621.1(targeted)-624.9(antitumor)-627.8(effect)]TJ 0 -1.1284 TD [(against)-452.6(mouse)-455(breast)-461.5(carcinoma.)]TJ /F6 1 Tf 14.1075 0 TD (Biomaterials)Tj /F5 1 Tf 5.6296 0 TD [(34:)-451.2(6818)]TJ -19.7371 -1.1223 TD [(6828,)-330(2013.)]TJ -1.7505 -1.1284 TD [(67.)-500.5(Tang)-372.6(L-Y,)-372.2(Wang)-375.1(Y-C,)-369(Li)-373.7(Y,)-373.8(Du)-373.9(J-Z,)-369.8(and)-376.7(Wang)-369(J.)-371.4(Shell-)]TJ 1.7505 -1.1223 TD 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