Development of red-light cleavable PEG-PLA nanoparticles as delivery systems for cancer therapy.

The development of targeted delivery systems can improve the selectivity of cancer drugs. Additionally, a system that promotes the controlled delivery of the drug triggered by an external stimulus in the exact target tissue is highly desirable. Regarding the light stimulus, the NIR window (650-950 nm) is the most suitable due to its higher capacity of penetration in human tissues and less harmful effects on normal cells. In this work, new red-light-responsive nanoparticles for doxorubicin delivery were developed. The nanoparticles were based on cleavable di-block copolymers of poly(ethylene glycol) (PEG) and poly(lactic acid) (PLA) linked by a red-light sensitive segment (1,2-bis(2-hydroxyethylthio)ethylene, BHETE). The PEG-BHETE-PLA copolymers were synthesized under mild conditions and exhibited a narrow polydispersity. The nanoparticles presented a size between 53 and 133 nm, with a doxorubicin loading capacity between 1.2 and 4.4 wt%. Release study of the encapsulated doxorubicin confirms the light-triggered nanoparticle disassembly process. In vitro cytotoxicity tests in MCF7 cell line, for the light-triggered nanoparticles, showed a decrease in cancer cells' viability higher than 25% compared to non-irradiated cells. Due to the promising results obtained with the light-sensitive PEG-BHETE-PLA nanoparticles, these materials have great potential to be used in drug delivery systems for cancer therapy.