Enhancing the Antitumor Effect of Doxorubicin with Photosensitive Metal-Organic Framework Nanoparticles against Breast Cancer

Mol Pharm. 2021 Aug 2;18(8):3026-3036. doi: 10.1021/acs.molpharmaceut.1c00249. Epub 2021 Jul 2.

Abstract

Breast cancer is one of the most common malignant tumors in women. The existence of multiple breast cancer subtypes often leads to chemotherapy failure or the development of drug resistance. In recent years, photodynamic therapy has been proven to enhance the sensitivity of tumors to chemotherapeutic drugs. Porphyrin-based metal-organic framework (MOF) materials could simultaneously be used as carriers for chemotherapy and photosensitizers in photodynamic therapy. In this paper, doxorubicin hydrochloride (DOX) was loaded in porphyrin MOFs, and the mechanism of the synergistic effect of the DOX carriers and photodynamic therapy on breast cancer was investigated. In vitro and in vivo experiments have shown that MOFs could prolong the residence time of DOX in tumor tissues and promote the endocytosis of DOX by tumor cells. In addition, adjuvant treatment with photodynamic therapy can promote breast cancer tumors to resensitize to DOX and synergistically enhance the chemotherapy effect of DOX. Therefore, this study can provide effective development ideas for reversing drug resistance during breast cancer chemotherapy and improving the therapeutic effect of chemotherapy on breast cancer.

Keywords: breast cancer; doxorubicin hydrochloride; metal−organic framework materials; photodynamic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Drug Liberation
  • Endocytosis / drug effects
  • Female
  • Humans
  • MCF-7 Cells
  • Metal Nanoparticles / chemistry*
  • Metal-Organic Frameworks / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticle Drug Delivery System / chemistry*
  • Photochemotherapy / methods*
  • Photosensitizing Agents / chemistry*
  • Porphyrins / chemistry
  • Tissue Distribution / drug effects
  • Treatment Outcome
  • Tumor Burden / drug effects

Substances

  • Antibiotics, Antineoplastic
  • Metal-Organic Frameworks
  • Nanoparticle Drug Delivery System
  • Photosensitizing Agents
  • Porphyrins
  • Doxorubicin