Hybrid Nanoparticles of Extracellular Vesicles and Gemcitabine Prodrug-Loaded Liposomes with Enhanced Targeting Ability for Effective PDAC Treatment

ACS Appl Bio Mater. 2024 Sep 16;7(9):6025-6033. doi: 10.1021/acsabm.4c00658. Epub 2024 Sep 4.

Abstract

Liposomes are applied to various anticancer treatments as representative drug delivery carriers. However, liposomes do not have their own targeting properties; therefore, there are limitations in drug delivery to specific tissues or cells. High targetability in drug delivery is an important factor in improving bioavailability and drug efficacy and reducing side effects; recent research has been actively investigated to modify the surface of liposomes to give them specific functions. In this study, we studied a drug delivery system for anticancer treatment that enhances targeting ability through fusion with exosomes on the surface of liposomes. We designed exosome-liposome hybrid nanoparticles loaded with a gemcitabine prodrug as a treatment for pancreatic ductal adenocarcinoma (PDAC). Membrane fusion with exosomes shows excellent targeting ability to pancreatic cancer cells due to intrinsic targeting ability and expansion of the macropinocytosis pathway.

Keywords: PDAC; exosome; gemcitabine prodrug; hybrid nanoparticle; liposome; target drug delivery.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Carcinoma, Pancreatic Ductal* / drug therapy
  • Carcinoma, Pancreatic Ductal* / metabolism
  • Carcinoma, Pancreatic Ductal* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Deoxycytidine* / analogs & derivatives
  • Deoxycytidine* / chemistry
  • Deoxycytidine* / pharmacology
  • Drug Delivery Systems
  • Drug Screening Assays, Antitumor*
  • Extracellular Vesicles* / chemistry
  • Extracellular Vesicles* / metabolism
  • Gemcitabine*
  • Humans
  • Liposomes* / chemistry
  • Materials Testing
  • Nanoparticles* / chemistry
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology
  • Particle Size*
  • Prodrugs* / chemistry
  • Prodrugs* / pharmacology

Substances

  • Gemcitabine
  • Deoxycytidine
  • Prodrugs
  • Liposomes
  • Biocompatible Materials
  • Antineoplastic Agents