Antibody fragment-conjugated polymeric micelles incorporating platinum drugs for targeted therapy of pancreatic cancer

被引：112

作者：

Ahn, Jooyeon ^{[1
]}

Miura, Yutaka ^{[2
]}

Yamada, Naoki ^{[4
]}

Chida, Tsukasa ^{[1
]}

Liu, Xueying ^{[2
]}

Kim, Ahram ^{[1
]}

Sato, Ryuta ^{[5
]}

Tsumura, Ryo ^{[5
]}

Koga, Yoshikatsu ^{[5
]}

Yasunaga, Masahiro

Nishiyama, Nobuhiro ^{[4
]}

Matsumura, Yasuhiro ^{[5
]}

Cabral, Horacio ^{[1
]}

Kataoka, Kazunori ^{[1
,2
,3
]}

机构：

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

[2] Univ Tokyo, Grad Sch Med, Ctr Dis Biol & Integrat Med, Div Clin Biotechnol,Bunkyo Ku, Tokyo 1130033, Japan

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

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

[5] Natl Canc Ctr Hosp East, Div Dev Therapeut, Kashiwa, Chiba 2778577, Japan

来源：

BIOMATERIALS | 2015年 / 39卷

基金：

日本学术振兴会;

关键词：

Drug delivery; Platinum; Micelle; Nanoparticle; Chemotherapy; BLOCK-COPOLYMER MICELLES; TISSUE FACTOR; ANTITUMOR-ACTIVITY; CYTOTOXIC DRUG; DISULFIDE BOND; GENE DELIVERY; BREAST-CANCER; SOLID TUMORS; IN-VIVO; IMMUNOMICELLES;

D O I：

10.1016/j.biomaterials.2014.10.069

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Antibody-mediated therapies including antibody-drug conjugates (ADCs) have shown much potential in cancer treatment by tumor-targeted delivery of cytotoxic drugs. However, there is a limitation of pay-loads that can be delivered by ADCs. Integration of antibodies to drug-loaded nanocarriers broadens the applicability of antibodies to a wide range of therapeutics. Herein, we developed antibody fragment-installed polymeric micelles via maleimide-thiol conjugation for selectively delivering platinum drugs to pancreatic tumors. By tailoring the surface density of maleimide on the micelles, one tissue factor (TF)-targeting Fab' was conjugated to each carrier. Fab'-installed platinum-loaded micelles exhibited more than 15-fold increased cellular binding within 1 h and rapid cellular internalization compared to non-targeted micelles, leading to superior in vitro cytotoxicity. In vivo, Fab'-installed micelles significantly suppressed the growth of pancreatic tumor xenografts for more than 40 days, outperforming non-targeted micelles and free drugs. These results indicate the potential of Fab'-installed polymeric micelles for efficient drug delivery to solid tumors. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：23 / 30

页数：8

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