Phenylboronic Acid-Installed Polymeric Micelles for Targeting Sialylated Epitopes in Solid Tumors

被引：344

作者：

Deshayes, Stephanie ^{[1
]}

Cabral, Horacio ^{[2
]}

Ishii, Takehiko ^{[2
]}

Miura, Yutaka ^{[3
,4
]}

Kobayashi, Shutaro ^{[1
]}

Yamashita, Takashi ^{[5
]}

Matsumoto, Akira ^{[6
]}

Miyahara, Yuji ^{[6
]}

Nishiyama, Nobuhiro ^{[7
]}

Kataoka, Kazunori ^{[1
,2
,4
,8
]}

机构：

[1] Univ Tokyo, Grad Sch Engn, Dept Mat Engn, Bunkyo Ku, Tokyo 1138656, Japan

[2] Univ Tokyo, Grad Sch Engn, Dept Bioengn, Bunkyo Ku, Tokyo 1138656, Japan

[3] Univ Tokyo, Grad Sch Engn, Div Tissue Engn, Bunkyo Ku, Tokyo 1138656, Japan

[4] Univ Tokyo, Grad Sch Engn, Ctr Dis Biol & Integrat Med, Bunkyo Ku, Tokyo 1138656, Japan

[5] Tokyo Univ Sci, Grad Sch Sci & Technol, Dept Pure & Appl Chem, Noda, Chiba 2788510, Japan

[6] Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Chiyoda Ku, Tokyo 1010062, Japan

[7] Tokyo Inst Technol, Chem Resources Lab, Div Polymer Chem, Midori Ku, Yokohama, Kanagawa 2268503, Japan

[8] Univ Tokyo, Ctr NanoBio Integrat, Bunkyo Ku, Tokyo 1138656, Japan

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2013年 / 135卷 / 41期

基金：

日本学术振兴会;

关键词：

SIALIC-ACID; CANCER-CHEMOTHERAPY; BLOCK-COPOLYMER; MELANOMA-CELLS; DRUG; THERAPEUTICS; NANOCARRIERS; ACCUMULATION; RECOGNITION; ERYTHROCYTE;

D O I：

10.1021/ja406406h

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

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

引用

页码：15501 / 15507

页数：7

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