Light-Triggered Clustered Vesicles with Self-Supplied Oxygen and Tissue Penetrability for Photodynamic Therapy against Hypoxic Tumor

Smart nanocarriers are of particular interest for highly effective photodynamic therapy (PDT) in the field of precision nanomedicine. Nevertheless, a critical challenge still remains in the exploration of potent PDT treatment against hypoxic tumor. Herein, light-triggered clustered polymeric vesicles for photoinduced hypoxic tumor ablation are demonstrated, which are able to deeply penetrate into the tumor and simultaneously afford oxygen supply upon light irradiation. Hydrogen peroxide (H2O2) and poly(amidoamine) dendrimer conjugating chlorin e6/cypate (CC-PAMAM) are coassembled with reactive-oxygen-species-responsive triblock copolymer into the polymeric vesicles. Upon 805 nm irradiation, the vesicles exhibit the light-triggered thermal effect that is able to decompose H2O2 into O-2, which distinctly ensures the alleviation of tumor hypoxia at tumor. Followed by 660 nm irradiation, the vesicles are rapidly destabilized through singlet oxygen-mediated cleavage of copolymer under light irradiation and thus allow the release of photoactive CC-PAMAM from the vesicular chambers, followed by their deep penetration in the poorly permeable tumor. Consequently, the light-triggered vesicles with both self-supplied oxygen and deep tissue penetrability achieve the total ablation of hypoxic hypopermeable pancreatic tumor through photodynamic damage. These findings represent a general and smart nanoplatform for effective photoinduced treatment against hypoxic tumor.