An NIR-activated polymeric nanoplatform with ROS- and temperature-sensitivity for combined photothermal therapy and chemotherapy of pancreatic cancer

Abstract

Nanomedicine has attracted growing attention due to its designability and functionality, as well as its excellent pharmacokinetics with limited side effects, and recently, combined therapies have become desirable as they can obtain enhanced therapeutic efficacy by using nanomedicine. Herein, we have reported a functional drug delivery system with a dual response to temperature and reactive oxygen species to efficiently eliminate pancreatic cancer cells in a combined therapy strategy. Functional micelles with camptothecin (CPT) in the core and indocyanine green (ICG) on the surface could effectively accumulate in tumor sites through the EPR effect. The ROS in the tumor microenvironment trigger the conversion of an amino-based copolymer to a carboxy based copolymer, releasing the loaded ICG to reduce the size of the micelles with high penetration in tumor tissue. On the one hand, under 808 nm light irradiation, the micelles will produce the heat to kill tumor cells via photothermal therapy. On the other hand, the generated heat could further trigger the transition of a copolymer from a hydrophobic to a hydrophilic state, releasing the loaded CPT into the deep tumor cells to achieve chemotherapy. The in vitro and in vivo experiments revealed that this combined therapy could combat pancreatic cancer cells with an enhanced therapeutic effect.