pH-induced in suit aggregation of Cu2-xSe-POED with extended tumor retention for enhanced chemodynamic /photothermal therapy

Various functional nanoparticle platforms have been used as alternative approaches for tumor treatment such as chemodynamic (CDT) and photothermal therapies (PTT). However, the tumor microenvironment with dense extracellular matrices and increased interstitial fluid pressure is adverse for enrichment and retention of nanoparticles. Herein, a pH-sensitive Cu 2-x Se-POED nanoparticles (CS-POED NPs) platform is developed to promote the hydrophilic-hydrophobic transition, that contribute to the formation of CS aggregates with large size in tumor tissue. pH-sensitivity of CS-POED NPs results from modifying the surface with pH-sensitive poly(ethylene glycol)-ortho ester-dihydrolipoic acid (POED). The accumulation of CS-POED NPs led to a Fenton-like reaction, generating considerable amounts of ROS to boost the effectiveness of CDT. Meanwhile, the agglomeration CS-POED NPs prolongs their tumor retention resulting in enhanced PTT. According to in vitro and in vivo studies, CS-POED NPs substantially kills tumor cells with laser irradiation, leading to a significant regression of the tumors. In addition, CS-POED NPs have exhibited a favorable biosafety profile based on their in vitro and in vivo evaluations. The novel pH-sensitive CS-POED nanoparticles platform certainly offers a new strategy for enhanced chemodynamic/photothermal tumor therapy.