Design of Organic Charge Transfer Complex Nanoparticles for Biomedical Applications

Description

Therapeutic agents with good near-infrared (NIR) responses are highly desired for tumor phototherapy applications, including photothermal and photodynamic therapies (PTT and PDT). Photoexcitation activates these materials to generate excessive heat in PTT or cytotoxic reactive oxygen species (ROS) in PDT to kill cancer cells. While PTT and PDT have been demonstrated to have much initial success, one limitation of their wider applications is the availability of therapeutics with high performance under NIR-IR excitation, which enables deeper tissue penetration and has better biosafety.To date, development of therapeutic agents with strong NIR absorption and excellent photoconversion efficiency for phototherapy is a hot topic as shown in serval important publications (Nature Photonics. 8, 455 (2014), Nature comm., 10, 767 (2019); 10, 1192 (2019); 10, 2206 (2019)). While there are some reports on PTT agents with absorption peaks higher than 800 nm, PDT agents with absorption peak beyond 800 nm are rare. The rarity of high performance NIR PTT/PDT agent is an obvious hurdle to be overcome. More importantly, complicated synthesis processes are usually required to prepare these materials. So far, there are only a handful of commercially available materials with good performance under ~ 800 nm excitation, and none of them shows promising PDT performance at long wavelength beyond 1000 nm.In our preliminary studies, PI and his team have prepared a new generation of water-dispersible organic nanoparticles with photoresponse up to 1500 nm based on charge transfer complexes (CTCs) formed between commercially available donor (D) and acceptor (A) materials. In this project, we propose to further study such CTC systems systematically, and develop basic design rules to select D and A materials for preparing high performance CTC nanoparticles for PTT and/or PDT applications. Results obtained in this work will generate knowledge on optimizing combinations of commercial D and A materials for shifting their absorption peaks from visible light to NIR in their CTCs. These CTC nanoparticles will be further characterized in term of their PTT/PDT performance, biosafety in vitro using different cell lines. Selected systems with good PTT/PDT performance and biocompatibility will be tested in vivo for developing potential high performance anticancer therapeutics under NIR irradiations.