A Charge Reversible Self‐Delivery Chimeric Peptide with Cell Membrane‐Targeting Properties for Enhanced Photodynamic Therapy

The cell membrane is the most important protective barrier in living cells and cell membrane targeted therapy may be a high‐performance therapeutic modality for tumor treatment. Here, a novel charge reversible self‐delivery chimeric peptide C 16 –PRP–DMA is developed for long‐term cell membrane targeted photodynamic therapy (PDT). The self‐assembled C 16 –PRP–DMA nanoparticles can effectively target to tumor by enhanced permeability and retention effect without additional carriers. After undergoing charge reverse in acidic tumor microenvironment, C 16 –PRP–DMA inserts into the tumor cell membrane with a long retention time of more than 14 h, which is very helpful for in vivo applications. It is found that under light irradiation, the reactive oxygen species generated by the inserted C 16 –PRP–DMA would directly disrupt cell membrane and rapidly induce cell necrosis, which remarkably increases the PDT effect in vitro and in vivo. This novel self‐delivery chimeric peptide with a long‐term cell membrane targeting property provides a new prospect for effective PDT of cancer.