Methoxypoly(ethylene glycol)-block-poly(L-glutamic acid)-loaded cisplatin and a combination with iRGD for the treatment of non-small-cell lung cancers

Macromol Biosci. 2012 Nov;12(11):1514-23. doi: 10.1002/mabi.201200145. Epub 2012 Oct 15.

Abstract

CDDP is loaded into methoxypoly(ethylene glycol)-block-poly(L-glutamic acid) (mPEG-b-PLG), and a combination with iRGD is applied for NSCLC chemotherapy. The CDDP-loaded micelles show sustained cisplatin release in PBS, dose- and time-dependent inhibition to HeLa and A549 cell proliferation, and no apparent hemolysis activities. In in vivo studies using subcutaneous NSCLC xenograft models (A549), both free CDDP and CDDP-loaded micelles show an evident anti-tumor effect. However, the toxicity of CDDP is significantly reduced in the cases of CDDP-loaded micelles and co-administration with iRGD, and the survival time is prolonged by over 30%. Therefore, mPEG-b-PLG-loaded cisplatin and the combination with iRGD provides a promising new therapy for NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cisplatin / chemistry
  • Cisplatin / pharmacokinetics
  • Cisplatin / pharmacology*
  • Drug Carriers / chemical synthesis*
  • Humans
  • Hydrogen-Ion Concentration
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Micelles
  • Microscopy, Electron, Transmission
  • Peptides, Cyclic / chemistry*
  • Polyethylene Glycols / chemical synthesis*
  • Polyglutamic Acid / analogs & derivatives*
  • Polyglutamic Acid / chemical synthesis
  • Survival Rate
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Micelles
  • Peptides, Cyclic
  • cyclic arginine-glycine-aspartic acid peptide
  • methoxypoly(ethylene glycol)-block-poly(glutamic acid)
  • Polyglutamic Acid
  • Polyethylene Glycols
  • Cisplatin