A Targeted Erythrocyte Membrane-Encapsulated Drug-Delivery System with Anti-osteosarcoma and Anti-osteolytic Effects

ACS Appl Mater Interfaces. 2021 Jun 23;13(24):27920-27933. doi: 10.1021/acsami.1c06059. Epub 2021 Jun 14.

Abstract

Chemotherapy is one of the main treatment methods for osteosarcoma. However, conventional chemotherapy lacks targeting properties, and its long-term and extensive use will have serious side effects on patients. For this reason, a multifunctional nanodrug system (V-RZCD) targeting osteosarcoma was developed in this study. V-RZCD consists of two parts: (1) the core (ZCD), wherein calcium ions (Ca2+) and zoledronic acid (ZA) form a metal-organic framework for loading doxorubicin (DOX), and (2) the shell (V-R), a vascular endothelial growth factor (VEGF) ligand-modified red blood cell membrane nanovesicle. By targeting the VEGF, V-RZCD can specifically bind to the VEGF receptors that are highly expressed on the surface of osteosarcoma cells. Importantly, compared with free ZA and DOX, V-RZCD not only clearly inhibits the proliferation of osteosarcoma but also significantly inhibits osteolysis induced by osteosarcoma. In summary, V-RZCD represents a new way to treat osteosarcoma.

Keywords: VEGF; anti-osteolytic; membrane nanovesicle; osteosarcoma; zoledronic acid.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Bone Neoplasms / drug therapy
  • Calcium / chemistry
  • Cell Line, Tumor
  • Doxorubicin / chemistry
  • Doxorubicin / therapeutic use*
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Erythrocyte Membrane / chemistry
  • Erythrocyte Membrane / metabolism
  • Humans
  • Metal-Organic Frameworks / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Osteolysis / drug therapy*
  • Osteolysis / etiology
  • Osteosarcoma / complications
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / metabolism
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Vascular Endothelial Growth Factor A / chemistry
  • Vascular Endothelial Growth Factor A / metabolism
  • Zoledronic Acid / chemistry

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Metal-Organic Frameworks
  • Vascular Endothelial Growth Factor A
  • Zoledronic Acid
  • Doxorubicin
  • Receptors, Vascular Endothelial Growth Factor
  • Calcium