An Integrated Therapeutic Delivery System for Enhanced Treatment of Hepatocellular Carcinoma
An Integrated Therapeutic Delivery System for Enhanced Treatment of Hepatocellular Carcinoma
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增强肝细胞癌治疗的综合治疗输送系统
DOI：
10.1002/adfm.201706600
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发表时间：
2018-05
影响因子：
19
通讯作者：
Yin Jian
中科院分区：
文献类型：
--
作者：
Ye Zhou;Wu Wen Rui;Qin Yu Fei;Hu Jing;Liu Chao;Seeberger Peter H;Yin Jian
纳米材料有望用于治疗人类癌症，但将多种功能整合到单一药物载体系统中仍然具有挑战性。本文报道了一种用于人肝细胞癌（HCC）治疗的整合治疗递送系统，其基于罗丹明B（RhB）末端标记的阳离子聚[2-（二甲氨基）乙基甲基丙烯酸酯]（PDMAEMA）和配备有共价结合的半乳糖的疏水性聚（3-叠氮基-2-羟丙基甲基丙烯酸酯）（PGMA-N3）片段。该生物相容性和安全平台RhB‐ PDMAEMA 25 ‐c‐ PGMA 50 ‐Gal胶束（半乳糖胶束）提供了四个优点：（1）半乳糖配体通过靶向在HCC细胞系表面上过表达的脱唾液酸糖蛋白受体（ASGPR）来增强细胞摄取;（2）RhB末端标记促进用于体外和体内追踪的真实的时间成像;（3）酸性肿瘤微环境使载体系统质子化，用于有效的药物释放以及基因转染，（4）抗癌药物阿霉素（DOX）和B-细胞淋巴瘤2小干扰RNA（Bcl-2 siRNA）的共递送在皮下和原位HCC荷瘤小鼠模型中协同对抗肿瘤生长。这种整合的治疗递送系统具有未来临床HCC治疗的潜力。
Nanomaterials hold promise for the treatment of human carcinomas but integrating multiple functions into a single drug carrier system remains challenging. Herein, an integrated therapeutic delivery system for human hepatocellular carcinoma (HCC) treatment is reported, which is based on rhodamine B (RhB) end‐labeled cationic poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA) and hydrophobic poly(3‐azido‐2‐hydroxypropyl methacrylate) (PGMA‐N3) segments equipped with a covalently bound galactose. This biocompatible and safe platform RhB‐PDMAEMA25‐c‐PGMA50‐Gal micelles (Gal‐micelles) offers four advantages: (1) Galactose ligands enhance cellular uptake by targeting the asialoglycoprotein receptor (ASGPR) that is overexpressed on HCC cell lines surfaces; (2) RhB end‐labeling facilitates real‐time imaging for tracking both in vitro and in vivo; (3) the acidic tumor microenvironment protonates the carrier system for efficient drug release as well as gene transfection, (4) codelivery of anticancer drug doxorubicin (DOX) and B‐cell lymphoma 2 small interfering RNA (Bcl‐2 siRNA) works synergistically against tumor growth in both subcutaneous and orthotopic HCC bearing mouse models. This integrated therapeutic delivery system holds potential for future clinical HCC treatment.
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DOI：
10.1007/978-3-319-26788-3_2
发表时间：
2016-01-01
期刊：
FLUORESCENCE STUDIES OF POLYMER CONTAINING SYSTEMS
影响因子：
--
作者：
Karayianni, Maria;Pispas, Stergios
通讯作者：
Pispas, Stergios
影响因子：
16.6
作者：
Inoue-Yamauchi A;Jeng PS;Kim K;Chen HC;Han S;Ganesan YT;Ishizawa K;Jebiwott S;Dong Y;Pietanza MC;Hellmann MD;Kris MG;Hsieh JJ;Cheng EH
通讯作者：
Cheng EH
影响因子：
14
作者：
Fabian Suriano;R. Pratt;J. Tan;N. Wiradharma;Alshakim Nelson;Yi-Yan Yang;P. Dubois;J. Hedrick
通讯作者：
Fabian Suriano;R. Pratt;J. Tan;N. Wiradharma;Alshakim Nelson;Yi-Yan Yang;P. Dubois;J. Hedrick
影响因子：
13.5
作者：
Bruix, J;Llovet, JM
通讯作者：
Llovet, JM
影响因子：
8.8
作者：
Meyer T;Kirkwood A;Roughton M;Beare S;Tsochatzis E;Yu D;Davies N;Williams E;Pereira SP;Hochhauser D;Mayer A;Gillmore R;O'Beirne J;Patch D;Burroughs AK
通讯作者：
Burroughs AK