Erythrocyte Membrane-Camouflaged PCN-224 Nanocarriers Integrated with Platinum Nanoparticles and Glucose Oxidase for Enhanced Tumor Sonodynamic Therapy and Synergistic Starvation Therapy

ACS Appl Mater Interfaces. 2021 Jun 2;13(21):24532-24542. doi: 10.1021/acsami.1c05644. Epub 2021 May 21.

Abstract

Sonodynamic therapy (SDT) is a promising method for tumor treatment, but self-quenching property, low loading efficiency of sonosensitizers, and hypoxia tumor microenvironment (TME) hinder the efficiency of SDT. Herein, an erythrocyte membrane (EM)-camouflaged metal-organic framework (MOF) of PCN-224 nanoparticles (NPs) integrated with platinum (Pt) NPs as well as glucose oxidase (GOx) has been developed to overcome these limits. Porphyrin-based PCN-224 NPs are synthesized as a sonosensitizer with a large amount of well-organized porphyrin molecules while simultaneously acting as the nanocarriers (NCs) for Pt NPs and GOx. When the NCs are internalized by tumor cells, Pt NPs on their surface are able to utilize endogenous hydrogen peroxide (H2O2) to produce oxygen for the relief of tumor hypoxia, thus enhancing the SDT effect. After EM cloaking, the longer circulation time can improve biocompatibility in vivo and enhance accumulation in tumor tissue. Loaded GOx is beneficial to local glucose consumption and can realize the tumor starvation therapy effect. Consequently, these multifunctional NCs show amplified synergistic therapeutic effects of tumor SDT and starvation therapy, which can efficiently inhibit the tumor growth.

Keywords: erythrocyte membrane; metal−organic framework; sonodynamic therapy; starvation therapy; synergistic tumor therapy.

MeSH terms

  • Animals
  • Combined Modality Therapy
  • Drug Carriers*
  • Erythrocyte Membrane*
  • Glucose Oxidase / metabolism*
  • Metal Nanoparticles / administration & dosage*
  • Metal Nanoparticles / chemistry
  • Mice
  • Mice, Inbred ICR
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Platinum / chemistry*
  • Tumor Hypoxia*
  • Ultrasonic Therapy*
  • Xenograft Model Antitumor Assays

Substances

  • Drug Carriers
  • Platinum
  • Glucose Oxidase