Multifunctional protein-based self-assembled nanoplatform: overcoming hypoxic tumor microenvironment for enhanced imaging-guided photodynamic therapy

Abstract

Photodynamic therapy (PDT) has emerged as a promising modality for cancer treatment, but its efficacy is often limited by tumour hypoxia. Here, we report the development of a novel protein-based, self-assembled nanoplatform, CAT-I-BODIPY NPs (CIB NPs), to address this limitation. We first design and synthesize an I-BODIPY photosensitizer based on the heavy atom effect and modification of the electron-donating group, which exhibits excellent capabilities in generating reactive oxygen species and enabling near-infrared (NIR) fluorescence imaging. The incorporation of an oxygen-producing enzyme, catalase (CAT), within these nanoassemblies enables in situ oxygen generation to counteract hypoxic constraints. Controllable self-assembly by multiple supramolecular interactions into highly ordered architecture not only guarantees CAT's catalytic activity but also leads to excellent NIR fluorescence imaging ability and enhanced PDT efficacy. Notably, the visualization of optimal accumulation of CIB NPs within tumour sites 18 h post-injection offers precise PDT application guidance. Both in vitro and in vivo studies corroborate the remarkable anti-tumour efficacy of CIB NPs under NIR illumination, providing a significant advancement in PDT. The favourable biosafety profile of CIB NPs further emphasizes their potential for clinical application in hypoxic tumour therapy.