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An NIR-Guided Aggregative and Self-Immolative Nanosystem for Efficient Cancer Targeting and Combination Anticancer Therapy.

Nanosized drug delivery systems based on polymeric structures have been proven to be promising approaches for cancer treatments. However, few have been effective at selectively targeting cancer cells and releasing drug at desired tumor sites. Here, we report a "smart" polymeric nanoplatform, which could actively accumulate at tumor sites and dissociate to release encapsulated cargos upon the irradiation of a near-infrared (NIR) laser. This nanoplatform composed of a novel amphiphilic block copolymer poly(propylene sulfide)-poly( N-isopropylacrylamide- co- N, N-dimethylacrylamide) (PPS-P(NIPAM- co-DMAA)) formed spherical structures in aqueous solution and responded to both oxidants and elevated temperature. Upon laser irradiation at 808 nm, the NIR light was efficiently converted to local heat by the doxorubicin (DOX) and indocyanine green (ICG) co-loaded micelles for enhanced cell uptake and therapeutic efficacy. It showed that the micelles effectively accumulated at the tumor sites guided by the application of an NIR laser in in vivo studies, exhibiting a 6-time greater and much faster targeting effect compared to the nonirradiation group. The effective tumor growth inhibition by the drug-loaded micelles upon laser irradiation demonstrated significant tumor inhibition without regrowth in 16 days. This micellar nanoplatform for precise NIR-guided cancer targeting and combination therapy provides a novel and robust strategy for cancer therapy.