NIR-activatable and colorectal cancer-targeted lipid polymer hybrid nanoparticles: Design and in vivo assessment

The combination of photothermal therapy and chemotherapy based on nanocarriers is regarded as a promising strategy for enhancing therapeutic efficacy in cancer treatment. Despite the huge progress achieved in the past years, nanocarriers without further specific surface modification can be easily cleared by the immune system thus affecting the therapeutic outcomes. Thus, developing a nanoplatform for active-targeted drug delivery against cancer is of great necessity. Herein, multifunctional lipid-polymer hybrid nanoparticles (abbr. Cet-CINPs) with enhanced long circulation and active targeting ability were constructed by coating the PEGlyated phospholipids and PLGA hybrid core with cetuximab for efficient chemo-photothermal synergistic therapy. Cet-CINPs were prepared through an ultrasonic emulsification method for co-loading irinotecan and indocyanine green. It is demonstrated that Cet-CINPs have spherical morphology with particle size of 119.97 ± 0.93 nm and exhibited excellent dispersion stability in ultrapure water at 4 °C. In vivo experiments showed that compared with conventional drug-loaded nanoparticles without cetuximab modification (CINPs), Cet-CINPs effectively targeted irinotecan transport to Lovo tumor sites. Moreover, upon near-infrared laser irradiation, Cet-CINPs finally accomplished up to 96.71 ± 1.60% tumor inhibition with negligible damage to normal tissues and organs because of the chemo-photothermal combined effect. Therefore, the NIR-activatable and active-targeted lipid-polymer hybrid nanoparticles could provide a precise, efficient, and synergistic method that might have contributed to treatment in colorectal cancer therapy.