TY - JOUR
T1 - Hyaluronan-grafted particle clusters loaded with Mitomycin C as selective nanovectors for primary head and neck cancers
AU - Bachar, Gideon
AU - Cohen, Keren
AU - Hod, Roy
AU - Feinmesser, Raphael
AU - Mizrachi, Aviram
AU - Shpitzer, Thomas
AU - Katz, Odelia
AU - Peer, Dan
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - CD44
KW - Head and neck cancers
KW - Hyaluronan
KW - Nanomedicine
UR - http://www.scopus.com/inward/record.url?scp=79955761548&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955761548&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2011.03.040
DO - 10.1016/j.biomaterials.2011.03.040
M3 - Article
C2 - 21482433
AN - SCOPUS:79955761548
VL - 32
SP - 4840
EP - 4848
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 21
ER -