Tumor-targeted delivery of anticancer drugs has been extensively studied for several decades. However, elaborately designed smart carriers for drug delivery frequently fail in clinical trials because of the complexity and heterogeneity of tumor environments in vivo. To overcome those challenges, we introduce a dual-targeted drug delivery system using folate-decorated polymeric micelles that quickly degrade under light illumination, releasing the encapsulated drugs in a controllable manner. This work aims to evaluate the in vitro and in vivo therapeutic efficacies of ROS-sensitive polymeric micelles encapsulating meso-tetraphenylporphyrin (TPP) and paclitaxel as a photosensitizer and an anti-cancer drug, respectively. The polythioketal-based micelles were fabricated from the self-assembly of the amphiphilic block copolymer of poly(1,4-phenyleneacetone dimethylene thioketal) (PPADT) and polyethylene glycol (PEG) having a weight-average molecular weight of 19.2 kDa. TPP and paclitaxel were encapsulated within the micelles, whereby folic acid was decorated on the surface by incorporating folic acid-PEG-b-PPADT. The light-induced degradation of the micelles was confirmed using NMR and GPC. The thioketal bond in micelles was degraded rapidly by singlet oxygen generated by TPP, and the encapsulated paclitaxel were released from the micelles. The intravenous injections of micelless with a low paclitaxel dosage (1 mg kg-1), followed by visible light illumination on the tumor sites of HeLa- xenograft mouse model was performed. Folic acid facilitated the accumulation of the drugs on tumor sites about 3 times higher, and light-assisted paclitaxel release greatly increased the therapeutic efficacy of micelles as indicated in tumor-growth suppression analysis.

Light-triggered and ROS-mediated degradation of therapeutic nanoparticles for enhanced in vivo anticancer therapeutic efficacy

254th National Meeting (2017)

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