Smart Magnetic and Fluorogenic Photosensitizer Nanoassemblies Enable Redox‐Driven Disassembly for Photodynamic Therapy

Stimuli-responsive smart photosensitizer (PS) nanoassemblies that allow enhanced delivery and controlled release of PSs are promising for imaging-guided photodynamic therapy (PDT) of tumors. However, the lack of high-sensitivity and spatial-resolution signals and fast washout of released PSs from tumor tissues have impeded PDT efficacy in vivo. Herein, we report tumor targeting, redox-responsive magnetic and fluorogenic PS nanoassemblies (NP-RGD) synthesized via self-assembly of a cRGD- and disulfide-containing fluorogenic and paramagnetic small molecule (1-RGD) for fluorescence/magnetic resonance bimodal imaging-guided tumor PDT. NP-RGD show high r1 relaxivity but quenched fluorescence and PDT activity; disulfide reduction by glutathione (GSH) promotes efficient disassembly into a small-molecule probe (2-RGD) and an organic PS (PPa-SH), which could further bind with intracellular albumin, allowing prolonged retention and cascade activation of fluorescence and PDT to ablate tumors.