Near-Infrared-Light-Responsive Lipid Nanoparticles as an Intelligent Drug Release System for Cancer Therapy

Conventional chemotherapeutic drugs cause systemic side effects due to nonspecific interactions with healthy tissues, which significantly hinders their tolerability and efficacy. Herein, we developed an intelligent drug delivery system, in which the drug release can be triggered by near-infrared (NIR) light at the tumor locus, prohibiting damage to normal tissues. This light-responsive system was established based on lipid nanoparticles consisting of a eutectic mixture of lauric acid and stearic acid, which have a melting point at 39 °C. Anticancer drug doxorubicin and NIR-absorbing dye methylenebisacrylamide were coencapsulated into these nanoparticles, while cRGD and CD47 peptide were conjugated on their surfaces for tumor targeting and immune evasion. The resultant nanoparticles exhibited quick drug release in response to NIR irradiation, prominent photothermal effects, and good cancer-targeting ability. Furthermore, in vivo studies in multiple tumor models all showed that the nanoparticles could specifically accumulate at the tumor site and drastically reduce tumor size without systemic side effects, demonstrating the promising potential of this intelligent drug delivery system for future cancer treatment.