Light triggered selective ROS dependent autophagy by bioactive nanoliposomes for efficient cancer theranostics

Abstract

Light responsive nanoliposomes are being reported to induce cancer cell death through heat and reactive oxygen species (ROS). Nanoliposomes (CIR NLPs) encapsulating near-infrared (NIR) light-sensitive dye, IR780 and bioactive chlorophyll-rich fraction of Anthocephalus cadamba (CfAc) were synthesized and characterized. These CIR NLPs when activated by NIR light, displayed a localized synergistic cancer cell death under in-vitro and in-vivo conditions. We demonstrated NIR light mediated release of CfAc in cancer cells. The bioactive CfAc was selective in causing ROS generation (leading to autophagic cell death) in cancer cells while normal healthy cells were unaffected. An increase in the intracellular ROS leading to enhanced lipidation of microtubule-associated protein light chain 3 (LC-3 II) was observed only in cancer cells, while normal cells showed no increase in either ROS or LC-3 II. In-vivo analysis of CIR NLPs in orthotopic mouse model showed better anti-tumorigenic potential through combined effect (heat & CfAc effect). We report for the first time, induction of selective and localized, bioactive phyto-fraction mediated autophagic cancer cell death through NIR light trigger. The synergistic activation of ROS mediated autophagy by light triggered nanoliposomes can be a useful strategy for enhancing the anticancer potential of combinational therapies.