Synergistic Cancer Photochemotherapy via Layered Double Hydroxide-Based Trimodal Nanomedicine at Very Low Therapeutic Doses

The success of cancer therapy is always accompanied by severe side effects due to the high amount of toxic antitumor drugs that off-target normal organs/tissues. Herein, we report the development of a trifunctional layered double hydroxide (LDH) nanosystem for combined photochemotherapy of skin cancer at very low therapeutic doses. This nanosystem (ICG/Cu-LDH@BSA–DOX) is composed of acid-responsive bovine serum albumin–doxorubicin prodrug (BSA–DOX) and indocyanine green (ICG)-intercalated Cu-doped LDH nanoparticle. ICG/Cu-LDH@BSA–DOX is able to release DOX in an acid-triggered manner, efficiently and simultaneously generates heating and reactive oxygen species (ROS) upon 808 nm laser irradiation, and synergistically induces apoptosis of skin cancer cells. In vivo therapeutic evaluations demonstrate that ICG/Cu-LDH@BSA–DOX nearly eradicated the tumor tissues upon one-course treatment using very low doses of therapeutic agents (0.175 mg/kg DOX, 0.5 mg/kg Cu, and 0.25 mg/kg ICG) upon very mild 808 nm laser irradiation (0.3 W/cm2 for 2 min). This work thus provides a novel strategy to design anticancer nanomedicine for efficient combination cancer treatment with minimal side effects in clinical applications.