Antitumor activity of folate receptor-targeted liposomal doxorubicin in a KB oral carcinoma murine xenograft model

Pharm Res. 2003 Mar;20(3):417-22. doi: 10.1023/a:1022656105022.


Purpose: The expression of folate receptor (FR) is amplified in many types of human cancers. Previously, FR-targeted liposomal doxorubicin (f-L-DOX) has been shown to exhibit superior and selective cytotoxicity against FR(+) tumor cells in vitro compared to nontargeted liposomal doxorubicin (L-DOX). This study further investigates f-L-DOX for its antitumor efficacy in vivo using a murine tumor xenograft model.

Methods: F-L-DOX composed of DSPC/cholesterol/PEG-DSPE/ folate-PEG-DSPE (65:31:3.5:0.5, mole/mole) was prepared by polycarbonate membrane extrusion followed by remote loading of DOX. Athymic mice on a folate-free diet were engrafted with FR(+) KB cells. Two weeks later, these mice were treated with f-L-DOX, L-DOX, or free DOX in a series of six injections (given intraperitoneally on every fourth day at 10 mg/kg DOX) and monitored for tumor growth and animal survival. The plasma clearance profiles of the DOX formulations and the effect of dietary folate on plasma folate concentration were also analyzed.

Results: Plasma folate level remained in the physiologic range relative to that in humans. F-L-DOX exhibited an extended systemic circulation time similar to that of L-DOX. Mice that received f-L-DOX showed greater tumor growth inhibition and a 31% higher (p < 0.01) increase in lifespan compared to those that received L-DOX. Meanwhile, free DOX given at the same dose resulted in significant toxicity and was less effective in prolonging animal survival.

Conclusions: FR-targeted liposomes are a highly efficacious vehicle for in vivo delivery of anticancer agents and have potential application in the treatment of FR(+) solid tumors.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carrier Proteins / biosynthesis*
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology*
  • Fluorometry
  • Folate Receptors, GPI-Anchored
  • Folic Acid / metabolism
  • Humans
  • Injections, Intraperitoneal
  • KB Cells
  • Liposomes
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mouth Neoplasms
  • Neoplasm Transplantation
  • Receptors, Cell Surface*
  • Survival Analysis
  • Time Factors
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Carrier Proteins
  • Folate Receptors, GPI-Anchored
  • Liposomes
  • Receptors, Cell Surface
  • Doxorubicin
  • Folic Acid