title: Hyaluronan-grafted particle clusters loaded with Mitomycin C as selective nanovectors for primary head and neck cancers.
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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petah Tiqwa and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Gideon
authors.initials: G
authors.lastname: Bachar
authors.forename: Keren
authors.initials: K
authors.lastname: Cohen
authors.forename: Roy
authors.initials: R
authors.lastname: Hod
authors.forename: Raphael
authors.initials: R
authors.lastname: Feinmesser
authors.forename: Aviram
authors.initials: A
authors.lastname: Mizrachi
authors.forename: Thomas
authors.initials: T
authors.lastname: Shpitzer
authors.forename: Odelia
authors.initials: O
authors.lastname: Katz
authors.forename: Dan
authors.initials: D
authors.lastname: Peer
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008422:Materials Testing; D051379:Mice; D008875:Middle Aged; D016685:Mitomycin / Q000737:chemistry* / Q000627:therapeutic use*; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000627:therapeutic use; D010316:Particle Size
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D016685:Mitomycin; D006820:Hyaluronic Acid; D017239:Paclitaxel