Hypoxia-responsive Exatecan prodrug liposomes co-delivered with IR808 for synergistic chemo-photodynamic therapy of breast cancer.

ABSTRACT: To overcome the poor solubility, rapid clearance, and systemic toxicity of Exatecan, we developed a tumor-activated liposomal delivery system co-encapsulating a hypoxia-cleavable Exatecan-squalene prodrug (EXA PRO) and the photosensitizer IR808. The nanocarrier integrates photodynamic therapy-induced hypoxia with bioreductive drug activation, enabling spatiotemporally controlled release within the tumor microenvironment. The liposomes, formulated with pH-sensitive lipids, exhibited uniform size (∼136 nm), high encapsulation efficiency, and dual responsiveness to acidic pH and reductive stress. Upon near-infrared laser irradiation, IR808 generated reactive oxygen species and aggravated intratumoral hypoxia, thereby triggering the cleavage of the azobenzene linker and facilitating targeted r

SUBMITTER: Wang L 

PROVIDER: S-EPMC12766086 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature