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 ( ¹O ₂). 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&IR780@CS 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 ¹O ₂ production. Additionally, significant therapeutic efficacy for cancer treatment were observed in vivo after oral administration of 5-ALA&IR780@CS 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.