Professor Shengliang Li published in Nano Letters

Calcium, a crucial cellular signal, is involved in both physiological response and biological development. Biology and medical researchers have efficiently focused on the calcium signal because it is intimately linked to the onset and progression of many serious human disorders. In the past few decades, scientists have been attempting to manage calcium signals for accurately curing illnesses and controlling biological processes. Emerging technologies, such as optogenetics, have been developed to study calcium signal modulationin vivoandin vitroduring the past ten years and also yielded a number of significant findings in this field. However, there are still significant flaws and safety issues in the reported approaches, which seriously limit its future application. Therefore, remote control of the calcium signal in deep tissues with minimal safety remains a big challenge.

Recently, Prof. Shengliang Li's group cooperated with Prof. Xing Chengfen from the Hebei University of Technology and published a paper entitled Remote Manipulation of ROS-Sensitive Calcium Channel Using Near-Infrared-Responsive Conjugated Oligomer Nanoparticles for Enhanced Tumor Therapy In Vivo”in Nano Letters.In this work, a multifunctional nanocarrier system with a near infrared response has been developed, which can be applied to the regulation of calcium channels in cells and the death of tumor cells mediated by calcium cascade, thus achieving efficient and safe tumor clearance treatment effect in a living tumor model. Prof. Shengliang Li and Prof. Chengfen Xing are the corresponding authors of the paper.

Figure 1.The detailed design and work mechanism of NIR-responsive nanomedicine

In recent years, Prof. Shengliang Li's group has developed a series of drug systems and carrier systems with high phototherapy activities viaregulating the molecular structure and structure-activity relationship of NIR phototherapy drugs, thus realizing high-performance NIR tumor diagnosis and treatment combined effect (Adv. Mater.2022, 34, 2201263;Adv. Mater.2021, 33, 2102799;Adv. Mater.2020, 32, 2001146;Angew. Chem. Int. Ed.2021, 133, 11864;ACS Nano2020, 14, 13681;ACS Nano2020, 14, 9917;ACS Nano2019, 13, 12901;Adv. Sci.2021, 8, 2003972;Mater. Horiz.2021, 8, 571;Chem. Sci.2020, 11, 888). On the basis of the above works, the team recently cooperated with Prof. Xing Chengfen of Hebei University of Technology to construct a multi-functional nanocarrier based on NIR photosensitizer, which realized the regulation of calcium channels and calcium cascade-mediated tumor cell death. In this study, a multifunctional nano-carrier loaded with TRPM2 plasmid was established. On the one hand, the carrier system can release TRPM2 plasmid through the responsive cleavage of diselenide linker under the irradiation of NIR light, thus enhancing the expression of TRPM2 in tumor cells. On the other hand, the TRPM2 channel can be selectively activated and trigger intracellular Ca²⁺influx for activating the ROS−TRPM2−Ca²⁺cascade, including autophagy and mitochondrial dysfunction. Electrophysiological experiments further confirmed the remote and repetitive calcium signal regulation performance of NIR light. After intravenous injection, NIR-II fluorescence imaging confirmed that the CONs-mediated platform could effectively accumulate in the tumor site. At the same time, the calcium ion signal and cascade reaction initiated by low-dose NIR light irradiation can achieve high-efficiency anti-tumor therapeutic activity and have good biological safety.

The work realizes the simultaneous gene delivery and calcium signal regulation function within a multifunctional nano-carrier, and also provides a new idea for ion channel regulation and anti-tumor therapy.

Reference:Ning Li, Yijian Gao, Boying Li, Dong Gao, Hao Geng, Shengliang Li*, and Chengfen Xing,* Remote Manipulation of ROS-Sensitive Calcium Channel Using Near-Infrared-Responsive Conjugated Oligomer Nanoparticles for Enhanced Tumor Therapy In Vivo. Nano Lett. 2022, 22, 5427-5433.

Linker:https://pubs.acs.org/doi/10.1021/acs.nanolett.2c01472

Prof. Shengliang Li, is a distinguished professor of College of Pharmaceutical Sciences in Soochow University, and holds a principal investigator in the laboratory of Advanced Bio-Photon and Nanomedicine. He has co-authored 90 papers with over 3600 times of citation (H-Index 34) and 3 ESI Highly Cited Paper (ESI 1%). Prof. Shengliang Li holds 4 PCT patent applications and received 4 Chinese patents. He is a Young Editorial Board Member for Chinese Chemical Letters.