Anti-platelet agents augment cisplatin nanoparticle cytotoxicity by enhancing tumor vasculature permeability and drug delivery

Ambarish Pandey, Sasmit Sarangi, Kelly Chien, Poulomi Sengupta, Anne Laure Papa, Sudipta Basu, Shiladitya Sengupta

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Tumor vasculature is critically dependent on platelet mediated hemostasis and disruption of the same can augment delivery of nano-formulation based chemotherapeutic agents which depend on enhanced permeability and retention for tumor penetration. Here, we evaluated the role of Clopidogrel, a well-known inhibitor of platelet aggregation, in potentiating the tumor cytotoxicity of cisplatin nano-formulation in a murine breast cancer model. In vivo studies in murine syngeneic 4T1 breast cancer model showed a significant greater penetration of macromolecular fluorescent nanoparticles after clopidogrel pretreatment. Compared to self-assembling cisplatin nanoparticles (SACNs), combination therapy with clopidogrel and SACN was associated with a 4 fold greater delivery of cisplatin to tumor tissue and a greater reduction in tumor growth as well as higher survival rate. Clopidogrel enhances therapeutic efficiency of novel cisplatin based nano-formulations agents by increasing tumor drug delivery and can be used as a potential targeting agent for novel nano-formulation based chemotherapeutics.

Original languageEnglish (US)
Article number445101
JournalNanotechnology
Volume25
Issue number44
DOIs
StatePublished - Nov 7 2014

Keywords

  • cisplatin
  • clopidogrel
  • drug delivery
  • nanoparticles

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering
  • Electrical and Electronic Engineering

Fingerprint Dive into the research topics of 'Anti-platelet agents augment cisplatin nanoparticle cytotoxicity by enhancing tumor vasculature permeability and drug delivery'. Together they form a unique fingerprint.

  • Cite this