A tumor acidity-driven transformable polymeric nanoassembly with deep tumor penetration and membrane-anchoring capability for targeted photodynamic therapy.

In recent years, directly damaging cell membrane therapeutic modalities have attracted great attention in the field of cancer therapy due to their critical role in guaranteeing essential cellular function. In this study, the transformable nanoassembly PEG-Ce6@PAEMA, consisting of the photosensitizer polyethylene glycol-chlorin-e6 (PEG-Ce6) and tumor pH-sensitive polymer poly(2-azepane ethyl methacrylate) (PAEMA), was developed for highly efficient membrane-targeted photodynamic therapy. The PAEMA core is rapidly protonated at the acidic tumor pH, resulting in the disassembly of PEG-Ce6@PAEMA and regeneration of PEG-Ce6. Subsequently, the resultant PEG-Ce6 with a very small size (~2.6 kDa) ensures deep penetration into tumor tissue and direct and rapid anchoring to the cancer cell membrane, eventually achieving superior tumor growth inhibition under light irradiation. Thus, this tumor acidity-driven transformable polymeric nanoassembly provides a simple but efficient strategy for membrane targeting cancer therapy.