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Hypericin nanoparticles for self-illuminated photodynamic cytotoxicity based on bioluminescence resonance energy
Hao-Han Yu1, Qiu-Ping Deng2, Qing-Hua Zheng3
1Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210046, People's Republic of China; College of Food and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210046, People's Republic of China.
Abstract:
The purpose of this study was to investigate the self-sensitization of photosensitizer without an external light source to produce a photodynamic therapy (PDT) effect based on the principle of bioluminescence resonance energy transfer (PDT-BRET). First, we demonstrated that HeLa cells could efficiently express firefly luciferase (FLase) after the firefly luciferase gene was transfected with the FLase-gene plasmid (FLase-GP), and proved that FLase could act on the substrate firefly D-luciferin (FLuc) to produce photons. The generated photons activate the photosensitizer hypericin (Hyp) and induce cytotoxicity. Then, we successfully prepared carboxymethyl chitosan-modified poly(lactic-co-glycolic acid) nanoparticles (CPNPs) loaded with FLuc (FLuc-CPNPs) and with loaded Hyp (Hyp-CPNPs). Their physicochemical and pharmaceutical characteristics indicated that they were an excellent drug delivery system. Characterization of the biological effects showed that they could be located in the mitochondrial, had higher ROS generation and stronger cytotoxicity. In vivo results also showed that PDT-BRET was as effective as classic PDT. PDT-BRET and the related drug delivery system are expected to become a new platform for anticancer therapy.
