Chitosan nanoparticles for oral photothermally enhanced photodynamic therapy of colon cancer

Phototherapy exerts its anticancer effects by converting laser radiation energy into hyperthermia or reactive singlet oxygen (1O2). In this study, we developed chitosan nanoparticles (CS NPs) encapsulating both photothermal (IR780) and photodynamic (5-Aminolevulinic acid (5-ALA)) reagents for photothermally enhanced photodynamic therapy by noninvasive oral administration. The 5-ALA&[email protected] NPs were stable in acidic conditions similar to the gastric environment, which greatly improved drug oral absorption and local accumulation in subcutaneous mouse colon tumors (CT-26 cells) following oral gavage. Mechanistic studies revealed that the co-delivery system can lead to photothermally enhanced photodynamic effects against cancer cells by increasing oxidative stress, including the elevation of ROS, superoxide and 1O2 production. Additionally, significant therapeutic efficacy for cancer treatment were observed in vivo after oral administration of 5-ALA&[email protected] NPs, without causing any overt adverse effects. Our work highlights the great potential of photothermally enhanced photodynamic therapy by CS NPs for colon cancer management via oral route.