Loading mitomycin C inside long circulating hyaluronan targeted nano-liposomes increases its antitumor activity in three mice tumor models

Dan Peer, Rimona Margalit

Research output: Contribution to journalArticle

196 Scopus citations

Abstract

The frequent overexpression of the hyaluronan receptors CD44 and RHAMM in cancer cells opens the door for targeting by the naturally-occurring high-M r hyaluronan. This is the first time effective in vivo tumor targeting is reported for mitomycin C (MMC) loaded inside nano-sized hyaluronan-liposomes (denoted tHA-LIP). The severe adverse effects of free MMC made it a rational candidate for an effective targeted carrier. In vitro, loading MMC inside tHA-LIP increased drug potency 100-fold, in cells overexpressing, but not in cells underexpressing, hyaluronan receptors. Both types of liposomes were non-toxic and reduced MMC-related toxicity in healthy C57BL/6 mice. In 3 tumor models, BALB/c bearing C-26 solid tumors; C57BL/6 bearing B16F10.9 or (separately) D122 lung metastasis, tHA-LIP were long-circulating, 7-fold and 70-fold longer than nt-LIP and free MMC, respectively. tHA-LIP-mediated MMC accumulation in tumor-bearing lungs was 20% of injected dose, compared to 0.6% and 4% with free drug and nt-LIP, respectively. Tumor-free lungs showed low accumulation, irrespective of drug formulation. Key indicators of therapeutic responses, tumor progression, metastatic burden and survival, were superior (p < 0.001) in animals receiving MMC-loaded tHA-LIP, no treatment, MMC-loaded nt-LIP and free drug. In conclusion, tHA-LIP perform as tumor-targeted carriers, with promising prospects for treatment of tumors overexpressing hyaluronan receptors.

Original languageEnglish (US)
Pages (from-to)780-789
Number of pages10
JournalInternational Journal of Cancer
Volume108
Issue number5
DOIs
StatePublished - Feb 20 2004

Keywords

  • Bioadhesive liposomes
  • Drug delivery
  • Hyaluronan
  • Mitomycin C
  • Targeting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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