A self-delivery chimeric peptide for high efficient cell membrane-targeting low-temperature photothermal/photodynamic combinational therapy and metastasis suppression of tumor

Cellular barriers such as the cell membranes, lysosomes or nuclear pores of tumor cells hinder the drugs delivery and weaken the efficiency of traditional tumor therapies. Targeted destructing tumor cell membranes can quickly destroy cell homeostasis and kill cells without facing intracellular delivery barriers. Herein, we designed a self-delivery phototherapeutic chimeric peptide (CCP) for high efficient cell membrane-targeting combinational low-temperature photothermal therapy (LTPTT) and photodynamic therapy (PDT). The self-assembled CCP nanoparticles display remarkable tumor accumulation after systemic administration without additional carriers, avoiding the carriers related side toxicities. The CCPs are able to generate reactive oxygen species (ROS) and mild heat (<45 °C) locally at cell membrane and quickly induce immunogenic cell death to achieve efficient combinational LTPTT/PDT. The damage-associated molecular patterns released after cell membrane rupture effectively elicit antitumor immunity to eradicate residual tumor cells. With a single dosage and short-term near-infrared (NIR) light irradiation, CCPs significantly inhibit growth and metastasis of tumor, and prolong survival time of tumor-bearing mice. This work presents a unique cell membrane-targeting phototherapy strategy to kill tumor and suppress metastasis in an effective, safe and minimally invasive manner.