A Metal-Organic Nanoplatform Coassembled with Artesunate and Chlorin e6 for Synergistic Chemo/Photodynamic Cancer Therapy

ChemMedChem. 2026 Jan;21(2):e202501003. doi: 10.1002/cmdc.202501003.

Abstract

Antitumor efficacy based on conventional chemodynamic therapy (CDT) is frequently constrained by insufficient endogenous H2O2 and the limitations of monotherapy. Herein, we developed a metal-organic nanoplatform (CA-Fe NPs). This platform was fabricated through Fe3+-driven coordination assembly of artesunate (AS) and chlorin e6 (Ce6), facilitating preferential tumor accumulation via the enhanced permeability and retention (EPR) effect. Upon cellular internalization and 660 nm laser irradiation, the nanodrug enables a synergistic combination of Ce6-mediated photodynamic therapy (PDT) and AS-induced oxidative stress, which collaboratively amplifies intracellular reactive oxygen species (ROS) generation. This cascade induces mitochondrial membrane potential collapse, leading to extensive apoptotic cell death (77.5%). In a 4T1 tumor-bearing mouse model, this approach achieved marked tumor suppression with an excellent safety profile, offering a promising strategy for combination therapy.

Keywords: chemodynamic therapy; combination therapy; photodynamic therapy; reactive oxygen species; synergistic effect.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Artesunate* / chemistry
  • Artesunate* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chlorophyllides
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Metal-Organic Frameworks* / chemistry
  • Metal-Organic Frameworks* / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Photochemotherapy*
  • Photosensitizing Agents* / chemical synthesis
  • Photosensitizing Agents* / chemistry
  • Photosensitizing Agents* / pharmacology
  • Porphyrins* / chemistry
  • Porphyrins* / pharmacology
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship

Substances

  • Chlorophyllides
  • phytochlorin
  • Porphyrins
  • Artesunate
  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Photosensitizing Agents
  • Metal-Organic Frameworks