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

Nanotechnology. 2014 Nov 7;25(44):445101. doi: 10.1088/0957-4484/25/44/445101. Epub 2014 Oct 10.


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.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Cell Line, Tumor
  • Cisplatin / chemistry
  • Cisplatin / therapeutic use*
  • Clopidogrel
  • Drug Delivery Systems / methods*
  • Mammary Neoplasms, Animal / blood supply
  • Mammary Neoplasms, Animal / drug therapy*
  • Mice
  • Mice, Inbred BALB C
  • Nanospheres / chemistry
  • Nanospheres / therapeutic use*
  • Permeability
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*


  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Cisplatin