Cyanine-based polymeric nanoplatform with microenvironment-driven cascaded responsiveness for imaging-guided chemo-photothermal combination anticancer therapy
How to overcome multistage biological barriers for nanocarriers in cancer therapy to obtain highly precise drug delivery is still a challenge. Herein, we prepared a multistage and cascaded switchable polymeric nanovehicle, self-assembled from polyethylene glycol grafted amphiphilic copolymer containing hydrophobic poly(ortho ester) and hydrophilic ethylenediamine-modified poly(glycidyl methacrylate) (PEG-g-p(GEDA-co-DMDEA) for imaging-guided chemo-photothermal combination anticancer therapy. Notably, a novel ATRP initiator containing cyanine dye was designed and attached to polymer, enabling nanovehicle with NIR-light induced photothermal and fluorescent properties. The PEG shell displayed tumor-microenvironment-induced detachment, resulting in surface charge change of nanovehicle from neutral to positive and thus enhanced cellular uptake. Subsequently, the hydrophobic pDMDEA hydrolyzed into hydrophilic segment in the acidic lysosome, leading to sufficient drug release. Finally, under the aid of photothermal, therapeutic drug DOX perfectly escaped from lysosome to exert chemotherapy. This well-defined polymeric nanoplatform promoted the development in designing novel theranostic polymeric nanovehcile for precise cancer therapy.