Conjugated Oligomer Nanoparticles for Type-I Photodynamic Therapy of Cancer with Near Infrared Radiation

Project: Research

View graph of relations

Description

Therapeutic agents with good near-infrared (NIR) responses are highly desired for tumor photodynamic therapy (PDT). In PDT, photosensitizers are excited by specific light to produce cytotoxic reactive oxygen species (ROS) for killing cancer cells. NIR excitation is strongly preferred for its deeper tissue penetration and less damage to healthy tissue. While PDT has experienced much recent development, wider applications is currently limited by their reduced therapeutic efficiency due to tumor hypoxia (i.e. low oxygen concentration in typical tumor environments). The low oxygen levels severely retard ROS generation by most PDT agents,which efficiency typically strong depends on the availability of environmental oxygen. To date, developing therapeutic materials with high NIR light-harvesting and PDT efficacy is a hot topic and holds great potential for cancer therapy as demonstrated in many important publications (Nature Chem. 2019, 11, 1041; Nat. Biomed. Eng. 2019, 3, 27; Nat. Photon. 2014, 8, 455; Nature Comm. 2020, 11, 1735; 2020, 11, 357, 2019, 10, 2412). While there are some reports on photothermal therapy (PTT) agents with absorption peaks beyond 800 nm, PDT agents with absorption peak >800 nm are rare. The rarity of high performance NIR PDT agent is an obvious hurdle to be overcome. More importantly, most reported PDT agents mainlygenerated singlet oxygen via commonly employed type-II PDT process, which is known as an oxygen-dependent modality and seriously limited by the natural hypoxia condition of tumor. On the other hand, the type-I PDT, which generates radicals instead of singlet oxygen to kill cancer cells, has been demonstrated to have much less dependence on oxygen supply. So far, there are some reports on type-I PDT agents able to be activated with visible light between 400 and 600 nm, and only a handful of them shows promising type-I PDT performance upon NIR excitation with wavelength >700 nm. In our preliminary studies, PI and his team have prepared a new generation of water dispersible organic oligomer nanoparticles with radical generation upon NIR exposure. Inparticular the PI has shown that attaching a stable radical to an oligomer molecule can enhance its radical generation ability in hypoxia. In this project, we propose to further explore such high-performance hypoxia-overcomin oligomer photosensitizers systematically, and develop rational molecular design rules to select donor (D), acceptor (A), π-linker and radical units forconstructing a series of type-I oligomer photosensitizers covering visible to NIR absorbance region for cancer PDT applications. Results to be achieved in this work will provide general guidelines for designing of D-A and D-A-radical structured oligomer materials for absorption tunable type-I PDT applications upon NIR irradiation. These oligomer nanoparticles will be further characterized in term of their PDT performances, biosafety in vitro using different cell lines. Optimized nanoparticles with high-performance PDT and biocompatibility in vitro will be tested for in vivo cancer therapeutic applications under NIR irradiations. 

Detail(s)

Project number9043412
Grant typeGRF
StatusNot started
Effective start/end date1/01/23 → …