NIR-activated dual-mode oxygen-generating and -delivering nanoplatform for enhanced photodynamic therapy of cervical cancer

Abstract

The clinical translation of photodynamic therapy (PDT) for cervical cancer is constrained by limited visible-light penetration and tumor hypoxia. These limitations are further aggravated by the oxygen-consuming nature of PDT itself. Although near-infrared (700–1700 nm, NIR) light activation can alleviate the penetration issue, overcoming hypoxia remains a paramount challenge. Herein, an oxygen self-sufficient theranostic nanoplatform, designated IFHFC nanoparticles (IFHFC NPs), is developed to synergistically enhance NIR-PDT by implementing a novel dual oxygen-supply strategy that integrates catalytic oxygen generation with physical oxygen delivery. The NPs deliver oxygen through two complementary routes. They catalyze the decomposition of endogenous hydrogen peroxide into oxygen and, under NIR irradiation, release stored oxygen to sustain local oxygen availability. This coordinated oxygenation alleviates hypoxia and increases cytotoxic reactive oxygen species generation. Both in vitro and in vivo studies confirm improved inhibition of cervical tumor growth. Overall, combining deep-tissue-penetrating NIR activation with dual-mode oxygenation offers a promising strategy for overcoming key barriers of PDT in solid tumor treatment.