Surface Functionalization of Polymeric Nanoparticles with Umbilical Cord-Derived Mesenchymal Stem Cell Membrane for Tumor-Targeted Therapy

ACS Appl Mater Interfaces. 2018 Jul 11;10(27):22963-22973. doi: 10.1021/acsami.8b05363. Epub 2018 Jun 26.

Abstract

Multiple cell plasma membranes have been utilized for surface functionalization of synthetic nanomaterials and construction of biomimetic drug delivery systems for cancer treatment. The natural characters and facile isolation of original cells facilitate the biomedical applications of plasma membranes in functionalizing nanocarriers. Human umbilical cord-derived mesenchymal stem cells (MSCs) have been identified to show tropism toward malignant lesions and have great advantages in ease of acquisition, low immunogenicity, and high proliferative ability. Here, we developed a poly(lactic- co-glycolic acid) (PLGA) nanoparticle with a layer of plasma membrane from umbilical cord MSC coating on the surface for tumor-targeted delivery of chemotherapy. Functionalization of MSC plasma membrane significantly enhanced the cellular uptake efficiency of PLGA nanoparticles, the tumor cell killing efficacy of PLGA-encapsulated doxorubicin, and most importantly the tumor-targeting and accumulation of the nanoparticles. As a result, this MSC-mimicking nanoformulation led to remarkable tumor growth inhibition and induced obvious apoptosis within tumor lesions. This study for the first time demonstrated the great potential of umbilical cord MSC plasma membranes in functionalizing nanocarriers with inherent tumor-homing features and the high feasibility of such biomimetic nanoformulations in cancer therapy.

Keywords: biomimetic nanoparticle; cancer therapy; plasma membrane; targeted drug delivery; umbilical cord mesenchymal stem cell.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / toxicity
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacokinetics
  • Biomimetic Materials / toxicity
  • Cell Membrane / chemistry*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Drug Delivery Systems / methods*
  • Drug Stability
  • Human Umbilical Vein Endothelial Cells / cytology
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Polymers
  • Surface Properties

Substances

  • Antineoplastic Agents
  • Polymers