An NIR guided aggregative and self-immolative nanosystem for efficient cancer targeting and combination anticancer therapy.

Nanosized drug delivery systems have offered promising approaches for cancer therapy. However, few was effective to selectively target cancer cells and release 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 near infrared laser (NIR) irradiation. This nanoplatform composed of a novel amphiphilic block copolymer poly(propylene sulphide)-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 doxorubicin (DOX) and indocyanine green (ICG) loaded micelles efficiently converted the NIR light to local heat for enhanced cell uptake and therapeutic efficacy. In vivo studies showed that the micelles effectively accumulated at the tumor sites guided by the application of NIR laser, exhibiting a 6-time higher and much faster targeting effect compared to the non-irradiation group. The tumor growth was effectively inhibited by the drug loaded micelles upon laser irradiation, demonstrating 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.