Amphiphilic fluorinated Aza-BODIPY alleviates hypoxia in solid tumors and enhances the photodynamic efficacy for breast cancer.

Photodynamic therapy (PDT) is an established modality for tumor treatment due to its high spatiotemporal precision and minimal invasiveness. Its efficacy is limited by tumor hypoxia, a hallmark of the solid tumor microenvironment that promotes malignant progression, and is exacerbated by PDT-induced oxygen consumption. To address this challenge, we synthesized an amphiphilic aza-BODIPY-based photosensitizer (PS) featuring hydrophobic perfluoroalkyl chains for enhanced oxygen delivery and hydrophilic oligo (ethylene glycol) chains for improved aqueous solubility. Such compound self-assembled into nanoparticles (BDP-F-NPs) in aqueous solution, which demonstrate exceptional colloidal stability and near-quantitative drug loading. The compound had significant singlet oxygen (1O₂) generation due to bromine functionalization at its 2,6-positions, while the perfluorocarbon (PFC) component enriches and stores oxygen. Upon 660 nm laser irradiation (120 J/cm2), BDP-F-NPs effectively inhibit tumor growth in vivo. This study presents a dual-functional nanoplatform combining oxygen supply and photosensitization, offering a clinically viable strategy to overcome hypoxia-associated therapy resistance in PDT.