Cancer-targeted reactive oxygen species-degradable polymer nanoparticles for near infrared light-induced drug release

Nanocarriers can be translocated to the peripheral region of tumor tissues through the well-known enhanced permeability and retention effects. However, a high dose of nanocarriers need to be injected due to the low delivery efficiency of nanocarriers, which can also increase the side effects of off-targeted nanocarriers in normal tissues. It was demonstrated that on-demand drug release from tumor-targeted nanocarriers can reduce the effective dosage of anti-cancer drugs by rapidly increasing the local drug concentration in the tumor tissue. Here we report a near-infrared (NIR) photodynamic method to trigger drug release from tumor-targeted polymer nanoparticles via reactive oxygen species (ROS)-mediated polymer degradation. Paclitaxel and silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) were co-encapsulated as an anti-cancer drug and photosensitizer, respectively, within biotin-decorated poly(ethylene glycol)-polythioketal micelles. Upon NIR light illumination under the maximum permissible exposure level, the photoexcited naphthalocyanine generated ROS cleaved the thioketal groups in the micelles to release the encapsulated paclitaxel. The photodynamically-induced release of paclitaxel dramatically reduced the half maximal inhibitory concentration of paclitaxel by 39.9-fold and eliminated lung adenocarcinoma at a concentration an order of magnitude smaller than its maximum tolerated dosage. Even under a simulated deep tissue condition with a tissue-like phantom, the NIR light-illuminated micelles exhibited a high level of cytotoxicity against the tumor cells and efficiently suppressed tumor growth. Our study demonstrates that photodynamic polymer degradation is an effective means to improve the anticancer drug efficacy of tumor-targeted micelles.