Biotinylated PAMAM dendrimers for intracellular delivery of cisplatin to ovarian cancer: role of SMVT

Anticancer Res. 2011 Mar;31(3):897-906.

Abstract

Aim: The aim of this study was to prepare biotinylated PAMAM dendrimers loaded with cisplatin and to evaluate the cytotoxicity in ovarian cancer cell lines.

Materials and methods: Biotinylated and unconjugated dendrimer-cisplatin complexes were investigated for encapsulation efficiency, in vitro cytotoxic activity and cellular accumulation of cisplatin in OVCAR-3, SKOV-3, A2780 (wild-type) and CP70 (A2780/CP70, cisplatin-resistant) cells.

Results: Encapsulation efficiency of cisplatin ranged from 5.33% to 21.10%. In vitro cytotoxic activity revealed that IC(50) values of dendrimer-cisplatin complexes were significantly lower than that of free cisplatin in OVCAR-3, SKOV-3 and CP70 cell lines. Cellular uptake data showed highest accumulation of platinum by PAMAMG(4) NH(2) dendrimer complexes of cisplatin in A2780 (19.41±0.85 μg/ml) and CP70 (25.25±1.25 μg/ml) cell lines in comparison with cisplatin uptake of only 1.77±0.351 μg/ml in A2780 and 2.31±0.421 μg/ml in CP70 cells.

Conclusion: In conclusion, biotinylated PAMAM dendrimers may be utilized as potential targeting agents for cisplatin delivery to ovarian cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biotinylation / drug effects
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • Dendrimers / pharmacology*
  • Drug Delivery Systems*
  • Female
  • Fluorescein-5-isothiocyanate / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hemolysis / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism*
  • Materials Testing
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Symporters / genetics
  • Symporters / metabolism

Substances

  • Dendrimers
  • PAMAM Starburst
  • Symporters
  • biotin transporter
  • Fluorescein-5-isothiocyanate
  • Cisplatin