H₂O₂-responsive biodegradable nanomedicine for cancer-selective dual-modal imaging guided precise photodynamic...

A tumor-related stimuli-activatable and biodegradable nanoplatform for tumor-selective imaging and effective photodynamic therapy (PDT) towards precision medicine is highly desirable but still greatly challenging. Here, we developed a novel H₂O₂-activatable and biodegradable nanomedicine (BSA-MBPB) by encapsulation of a single newly synthesized pro-photosensitizer (MBPB) with its photoactivity completely annihilated within bovine serum albumin (BSA) to achieve imaging-guided tumor-targeted effective PDT. BSA-MBPB can be decomposed and activated by H₂O₂ to not only produce the clinical photosensitizer methylene blue to recover its fluorescent, photoacoustic and photosensitizing properties for dual-modal imaging and cytotoxic singlet oxygen (¹O₂) generation, but also to simultaneously produce a GSH-depleting adjuvant quinone methide to boost the ¹O₂ yield, thus strengthening the efficacy of PDT. BSA-MBPB allows for highly efficient and accurate PDT without major side effects, offering potential as the next-generation nanomedicine towards clinical practice of precise PDT.