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Self-Assembly of Monomeric Hydrophobic Photosensitizers with Short Peptides Forming Photodynamic Nanoparticles with Real-Time Tracking Property and without the Need of Release in Vivo.

Employing nanoscaled materials as photosensitizer (PS) carriers is an effective strategy to solve the problem of poor solubility and low tumor selectivity of hydrophobic PS in photodynamic therapy (PDT), which compulsorily requires the PS release in PDT implementation. However, the complicated environment in vivo makes it difficult to precisely design and control the release process and the delivery process requires real-time tracking. Developing a delivery strategy of hydrophobic PS in the monomeric form with fluorescent emission and without consideration of the PS release in the PDT process, is in urgent demand. Herein, we report a versatile and potent strategy for fabrication of photodynamic nanoparticles (nanoPSs) with featuring the monomeric PS based on aromatic peptide-modulated self-assembly of porphyrin derivatives. Aromatic peptides within nanoPSs can isolate hydrophobic porphyrins from each other, resulting in monomeric porphyrin delivery with real-time fluorescence tracking property and avoiding self-aggregation and hence porphyrin release. Moreover, partially charged porphyrins tend to expose on the surface of nanoPSs, facilitating production and diffusion of 1O2. The highest 1O2 yield can be achieved with porphyrin loading as low as 6 wt %, reducing side effects of excessive porphyrin injection. The nanoPSs show enhanced PDT efficacy in vitro and in vivo leading to complete tumor eradication. This study highlights opportunities for development of active photodynamic nanoparticles and provides an alternative strategy for delivery of hydrophobic photosensitive drugs with enhanced therapeutic effects.