Professor Huabing Chen's group reports self-activated arsenic manganite nanohybrids in the Journal of Controlled Release

Arsenic trioxide (ATO) is an anti-tumor drug derived from traditional Chinese Medicine. It has achieved great success in the treatment of acute promyelocytic leukemia. High-dose ATO has a certain curative effect on solid tumors such as liver cancer, breast cancer, and prostate cancer, but the non-targeted distribution of high-dose ATO often causes serious toxic and side effects. How to improve the tumor targeting of arsenic agents, reduce their toxic side effects, and explore the combination therapy of arsenic therapy to improve the therapeutic effect of arsenic agents on solid tumors is the key focus of current research in cancer therapy.

In recent years, the research team of Chen Huabing of Soochow University and the team of Shen Junkang of the Second Affiliated Hospital have used the single-molecule albumin template to induce the biomineralization of drugs in the inner cavity of the protein by electrostatic adsorption, precipitation, coordination, etc., and constructed a series of drug-loaded single-molecule albumin nanoparticles to improve tumor imaging and therapeutic effects through targeted drug delivery. Based on the above work, the team recently reported a self-activating arsenic-manganese nanocomposite with tumor-targeting ability to achieve high-contrast magnetic resonance imaging (MRI) and arsenic therapy-photothermal/immune synergistic therapy for solid tumors (Scheme 1, J Control Release 2022, 350, 761-776).

Scheme 1.Self-activated As/Mn-NHs for high-contrast MRI and thermo/immuno-arsenotherapeutic synergy of ATO against solid tumors.

The research team introduced a controllable Mn²⁺/HAsO₃^2-biomineralization reaction in the albumin cavity to prepare a self-activating arsenic-manganese nanocomposite with tumor-targeted drug delivery ability. The arsenic-manganese nanocomplex can be decomposed under the stimulation of acidity and glutathione to generate Mn²⁺with high-contrast MRI imaging, and at the same time, it can significantly increase the concentration of arsenic in tumor cells, and induce tumor cell apoptosis and anti-tumor metastases through various pathways (Fig. 1), and significantly induce tumor immunogenic cell death (Fig. 2). The arsenic-manganese nanocomposite has a good therapeutic effect on triple-negative breast cancer, and it can be further combined with photothermal therapy or immunotherapy to enhance the inhibitory effect of orthotopic breast cancer and lung metastasis through synergistic effect (Fig. 3).

Fig. 1.Mechanisms of apoptosis and anti-metastasis in tumor cells after As/Mn-NHs treatment.

Fig. 2.Immunogenic cell death (ICD) effect has been inducedin 4T1 tumor cellsafter As/Mn-NHs treatment.

Fig. 3.Synergistic antitumor efficacy against both primary and metastatic breast tumors upon combination with concurrent thermo/immuno-therapy.

In summary, our rationally designed As/Mn-NHs with tumor targeting and stimuli-responsive cascade delivery show great promise in high-contrast imaging and arsenotherapy-based synergy, affording a clinically translational vehicle for visible and synergistic arsenotherapy against solid tumors.

References:Yanhua Zhai, Ming Liu, Tao Yang, Jie Luo, Chaogang Wei*, Junkang Shen*, Xue Song, Hengte Ke, Peng Sun, Miao Guo, Yibin Deng*, Huabing Chen*, Self-activated arsenic manganite nanohybrids for visible and synergistic thermo/immuno-arsenotherapy.J Control Release2022, 350, 761-776.

The original link:https://doi.org/10.1016/j.jconrel.2022.08.054