De novo design of polymeric carrier to photothermally release singlet oxygen for hypoxic tumor treatment

Intratumoral hypoxia extremely limits the clinic applications of photodynamic therapy (PDT). Endoperoxides allow thermally releasing singlet oxygen (¹O₂) in a defined quantity and offer promising opportunities for oxygen-independent PDT treatment of hypoxic tumors. However, previous composite systems by combining endoperoxides with photothermal reagents may result in unpredicted side effects and potential harmful impacts during therapy in vivo. Herein, we de novo design an all-in-one polymer carrier, which can photothermally release ¹O₂. The strategy has been demonstrated to effectively enhance the production of ¹O₂ and realize the photodamage in vitro, especially in hypoxic environment. Additionally, the polymer carrier accumulates into tumor after intravenous injection via the enhanced permeation and retention effects and accelerates the oxygen-independent generation of ¹O₂ in tumors.The oxidative damage results in good inhibitory effect on tumor growth. Realization of the strategy in vivo paves a new way to construct photothermal-triggered oxygen-independent therapeutic platform for clinical applications.