Dendrimer-platinate: a novel approach to cancer chemotherapy

Anticancer Drugs. 1999 Sep;10(8):767-76.

Abstract

A polyamidoamine (PAMAM) dendrimer generation 3.5 with a sodium carboxylate surface was conjugated to cisplatin giving a dendrimer-platinate (dendrimer-Pt; 20-25 wt% platinum) which was highly water soluble and released platinum slowly in vitro. In vivo the dendrimer-Pt and cisplatin were equi-active i.p. against i.p. L1210, and at high dose dendrimer-Pt given i.p. showed activity against i.p. B16F10 whereas cisplatin did not. Additionally, when administered i.v. to treat a palpable s.c. B16F10 melanoma, the dendrimer-Pt displayed antitumor activity whereas cisplatin was inactive. Measurement of platinum levels in blood and tissues after i.v. injection of cisplatin (1 mg/kg) or dendrimer-Pt (15 mg/kg)-the maximum tolerated dose (MTD) of these compounds-showed selective accumulation of the dendrimer-Pt in solid tumor tissue by the EPR effect (a 50-fold increase in area under curve compared with cisplatin). The dendrimer-Pt was also less toxic (3- to 15-fold) than cisplatin and thus has potential for further investigation as a novel antitumor approach.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Cell Survival / drug effects
  • Cisplatin / chemistry
  • Cisplatin / pharmacokinetics
  • Cisplatin / therapeutic use*
  • Dendrimers
  • Dose-Response Relationship, Drug
  • In Vitro Techniques
  • Male
  • Melanoma / drug therapy
  • Melanoma / pathology
  • Mice
  • Neoplasm Transplantation
  • Polyamines / chemistry*
  • Solubility
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Dendrimers
  • PAMAM Starburst
  • Polyamines
  • Cisplatin