Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles

Nanomedicine (Lond). 2013 May;8(5):687-98. doi: 10.2217/nnm.12.134. Epub 2012 Oct 17.

Abstract

Aim: Two unexplored aspects for irinotecan and cisplatin (I&C) combination chemotherapy are: actively targeting both drugs to a specific diseased cell type, and delivering both drugs on the same vehicle to ensure their synchronized entry into the cell at a well-defined ratio. In this work, the authors report the use of targeted polymeric nanoparticles (NPs) to coencapsulate and deliver I&C to cancer cells expressing the prostate-specific membrane antigen.

Materials & methods: Targeted NPs were prepared in a single step by mixing four different precursors inside microfluidic devices.

Results: I&C were encapsulated in 55-nm NPs and showed an eightfold increase in internalization by prostate-specific membrane antigen-expressing LNCaP cells compared with nontargeted NPs. NPs coencapsulating both drugs exhibited strong synergism in LNCaP cells with a combination index of 0.2.

Conclusion: The strategy of coencapsulating both I&C in a single NP targeted to a specific cell type could potentially be used to treat different types of cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antigens, Surface / metabolism
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacology*
  • Drug Delivery Systems*
  • Drug Synergism
  • Glutamate Carboxypeptidase II / metabolism
  • Humans
  • Irinotecan
  • Male
  • Nanoparticles / chemistry*
  • Polymers / chemistry
  • Prostate / drug effects*
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology

Substances

  • Antigens, Surface
  • Antineoplastic Agents
  • Polymers
  • Irinotecan
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Cisplatin
  • Camptothecin