Tumor microenvironment-activated HA@GOx/IR-820@MnO2 nanosheets for dual-modal imaging guided phototherapy of cervical cancer.

The clinical efficacy of photodynamic therapy (PDT) for solid tumors is severely constrained by the hypoxic tumor microenvironment. To address this issue, we developed a novel type of theranostic nanoplatform-HA@GOx/IR-820@MnO2 nanosheets (HGI-MnO2 NSs), based on hyaluronic acid (HA)-modified manganese dioxide nanosheets (MnO2 NSs) co-loaded with a near-infrared II (900-1700 nm, NIR-II) fluorescence emissive organic dye (IR-820) and glucose oxidase (GOx). This nanosystem is designed to self-replenish oxygen and amplify reactive oxygen species (ROS) generation through a cascade of catalytic reactions. The HGI-MnO2 NS continuously decomposes tumor-overexpressed hydrogen peroxide (H2O2) into oxygen, alleviating hypoxia and thereby enhancing IR-820-mediated PDT. Simultaneously, GOx consumes intratumoral glucose and generates H2O2in situ, which in turn serves as a substrate for MnO2, creating a self-sustaining cycle to augment therapeutic outcomes. Furthermore, the nanoplatform enables high-contrast NIR-II fluorescence imaging for precise tumor localization. Both in vitro and in vivo experiments demonstrate effective tumor suppression via effective PDT as well as strong photothermal therapy mediated by IR-820, along with great biocompatibility. This work presents a promising multifunctional nanoplatform for precise cervical cancer theranostics, particularly against hypoxic and resistant tumors.