Near-Infrared-Activated Lysosome Pathway Death Induced by ROS Generated from Layered Double Hydroxide-Copper Sulfide Nanocomposites

ACS Appl Mater Interfaces. 2020 Sep 9;12(36):40673-40683. doi: 10.1021/acsami.0c11739. Epub 2020 Aug 27.

Abstract

The overdeveloped lysosomes in cancer cells are gaining increasing attention toward more precise and effective organelle-targeted cancer therapy. It is suggested that rod/plate-like nanomaterials with an appropriate size exhibited a greater quantity and longer-term lysosomal enrichment, as the shape plays a notable role in the nanomaterial transmembrane process and subcellular behaviors. Herein, a biodegradable platform based on layered double hydroxide-copper sulfide nanocomposites (LDH-CuS NCs) is successfully prepared via in situ growth of CuS nanodots on LDH nanoplates. The as-prepared LDH-CuS NCs exhibited not only high photothermal conversion and near-infrared (NIR)-induced chemodynamic and photodynamic therapeutic efficacies, but also could achieve real-time in vivo photoacoustic imaging (PAI) of the entire tumor. LDH-CuS NCs accumulated in lysosomes would then generate extensive subcellular reactive oxygen species (ROS) in situ, leading to lysosomal membrane permeabilization (LMP) pathway-associated cell death both in vitro and in vivo.

Keywords: NIR-induced chemodynamic therapy; lipid peroxide; lysosome pathway death; photothermal; subcellular.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects
  • Cell Membrane Permeability / drug effects
  • Cells, Cultured
  • Copper / chemistry
  • Copper / metabolism
  • Copper / pharmacology*
  • Disease Models, Animal
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Hydroxides / chemistry
  • Hydroxides / metabolism
  • Hydroxides / pharmacology*
  • Infrared Rays
  • Lysosomes / chemistry
  • Lysosomes / metabolism*
  • Mammary Neoplasms, Experimental / diagnostic imaging
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / metabolism
  • Mice
  • Mice, Nude
  • Nanocomposites / chemistry*
  • Particle Size
  • Photoacoustic Techniques
  • Photothermal Therapy
  • Reactive Oxygen Species / metabolism*
  • Surface Properties

Substances

  • Antineoplastic Agents
  • Hydroxides
  • Reactive Oxygen Species
  • Copper
  • hydroxide ion
  • cupric sulfide