Hemocompatibility of folic-acid-conjugated amphiphilic PEG-PLGA copolymer nanoparticles for co-delivery of cisplatin and paclitaxel: treatment effects for non-small-cell lung cancer

Tumour Biol. 2016 Jun;37(6):7809-21. doi: 10.1007/s13277-015-4634-1. Epub 2015 Dec 22.

Abstract

In this study, we used folic-acid-modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (FA-PEG-PLGA) to encapsulate cisplatin and paclitaxel (separately or together), and evaluated their antitumor effects against lung cancer; this study was conducted in order to investigate the antitumor effects of the co-delivery of cisplatin and paclitaxel by a targeted drug delivery system. Blood compatibility assays and complement activation tests revealed that FA-PEG-PLGA nanoparticles did not induce blood hemolysis, blood clotting, or complement activation. The results also indicated that FA-PEG-PLGA nanoparticles had no biotoxic effects, the drug delivery system allowed controlled release of the cargo molecules, and the co-delivery of cisplatin and paclitaxel efficiently induces cancer cell apoptosis and cell cycle retardation. In addition, co-delivery of cisplatin and paclitaxel showed the ability to suppress xenograft lung cancer growth and prolong the survival time of xenografted mice. These results implied that FA-PEG-PLGA nanoparticles can function as effective carriers of cisplatin and paclitaxel, and that co-delivery of cisplatin and paclitaxel by FA-PEG-PLGA nanoparticles results in more effective antitumor effects than the combination of free-drugs or single-drug-loaded nanoparticles.

Keywords: CDDP; Co-delivery; Lung cancer; Nanoparticles; PTX.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects
  • Blood / drug effects*
  • Blood Coagulation / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacology*
  • Complement Activation / drug effects
  • Drug Carriers
  • Drug Compounding
  • Folic Acid / administration & dosage
  • Folic Acid / pharmacology*
  • Hemolysis / drug effects
  • Humans
  • Leukocyte Count
  • Lung Neoplasms / drug therapy*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles* / administration & dosage
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacology*
  • Polyesters / administration & dosage
  • Polyesters / chemistry
  • Polyesters / pharmacology*
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology*
  • Rabbits
  • Xenograft Model Antitumor Assays

Substances

  • Drug Carriers
  • Polyesters
  • polyethylene glycol-poly(lactide-co-glycolide)
  • Polyethylene Glycols
  • Folic Acid
  • Paclitaxel
  • Cisplatin