Hyaluronan-grafted particle clusters loaded with Mitomycin C as selective nanovectors for primary head and neck cancers

Gideon Bachar, Keren Cohen, Roy Hod, Raphael Feinmesser, Aviram Mizrachi, Thomas Shpitzer, Odelia Katz, Dan Peer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

CD44, a well-documented cell surface receptor, is involved in cell proliferation, migration, signaling, adhesion, differentiation and angiogenesis, which are important properties for normal and cancerous cell function. We recently developed particle clusters coated with hyaluronan (termed gagomers; GAG), and showed that they can deliver the insoluble drug paclitaxel directly into CD44-over-expressing tumors in a mouse tumor model. Here, we tested primary head and neck cancers (HNC) and normal cells taken from the same patient, and found that although CD44 expression in both types of cells was high, GAGs bind only to the cancerous cells in a selective manner. We next formulated the anti cancer agent mitomycin C (MMC) in the GAGs. MMC-based chemoradiation is a potential treatment for HNC, however, due to patient's toxicity, MMC is not part of the standard treatment of HNC. MMC encapsulation efficiency was about 70% with a half-life drug efflux of 1.2 ± 0.3 days. The Ex vivo study of the targeted MMC-GAG showed significant increase in the therapeutic effect on HNC cells (compared to free MMC), while it had no effect on normal cells taken from the same patient. These results demonstrate the specificity of the nanovectors towards head and neck cancers, which might be applicable as future therapy to many CD44-expressing tumors.

Original languageEnglish
Pages (from-to)4840-4848
Number of pages9
JournalBiomaterials
Volume32
Issue number21
DOIs
StatePublished - Jul 2011

Funding

FundersFunder number
Levy Family Trust
Alcon Foundation
European Commission
Israel Science Foundation181/10

    Keywords

    • CD44
    • Head and neck cancers
    • Hyaluronan
    • Nanomedicine

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