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Deshayes, Stephanie; Cabral, Horacio; Ishii, Takehiko; Miura, Yutaka; Kobayashi, Shutaro; Yamashita, Takashi; Matsumoto, Akira; Miyahara, Yuji; Nishiyama, Nobuhiro; Kataoka, Kazunori
Journal of the American Chemical Society, 10/2013, Volume: 135, Issue: 41Journal Article
Ligand-mediated targeting of nanocarriers to tumors is an attractive strategy for increasing the efficiency of chemotherapies. Sialylated glycans represent a propitious target as they are broadly overexpressed in tumor cells. Because phenylboronic acid (PBA) can selectively recognize sialic acid (SA), herein, we developed PBA-installed micellar nanocarriers incorporating the parent complex of the anticancer drug oxaliplatin, for targeting sialylated epitopes overexpressed on cancer cells. Following PBA-installation, the micelles showed high affinity for SA, as confirmed by fluorescence spectroscopy even at intratumoral pH conditions, i.e., pH 6.5, improving their cellular recognition and uptake and enhancing their in vitro cytotoxicity against B16F10 murine melanoma cells. In vivo, PBA-installed micelles effectively reduced the growth rate of both orthotopic and lung metastasis models of melanoma, suggesting the potential of PBA-installed nanocarriers for enhanced tumor targeting
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