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An Integrated Therapeutic Delivery System for Enhanced Treatment of Hepatocellular Carcinoma
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2018-03-12 , DOI: 10.1002/adfm.201706600 Zhou Ye 1, 2 , Wen-Rui Wu 3 , Yu-Fei Qin 3 , Jing Hu 1 , Chao Liu 3 , Peter H. Seeberger 2 , Jian Yin 1
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2018-03-12 , DOI: 10.1002/adfm.201706600 Zhou Ye 1, 2 , Wen-Rui Wu 3 , Yu-Fei Qin 3 , Jing Hu 1 , Chao Liu 3 , Peter H. Seeberger 2 , Jian Yin 1
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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.
中文翻译：
增强治疗肝细胞癌的综合治疗传递系统
纳米材料有望用于人类癌症的治疗，但是将多种功能整合到单个药物载体系统中仍然具有挑战性。本文报道了一种基于人丹参B（RhB）末端标记的阳离子聚甲基丙烯酸[2-（二甲氨基）乙基甲基丙烯酸]（PDMAEMA）和疏水性聚（3-叠氮基-2-甲基丙烯酸羟丙酯（PGMA-N 3）装有共价结合的半乳糖的片段。这种具有生物相容性且安全的平台RhB-PDMAEMA25-c-PGMA50-Gal胶束（Gal-胶束）具有四个优点：（1）半乳糖配体通过靶向在HCC细胞系表面过度表达的去唾液酸糖蛋白受体（ASGPR）来增强细胞摄取；（2）RhB末端标记有助于实时成像，以追踪体内和体外；（3）酸性肿瘤微环境使载体系统质子化，从而实现高效药物释放和基因转染；（4）抗癌药阿霉素（DOX）和B细胞淋巴瘤的代码传递2小干扰RNA（Bcl-2 siRNA）协同作用皮下和原位肝癌小鼠模型中的肿瘤生长。这种集成的治疗输送系统具有未来临床HCC治疗的潜力。
更新日期：2018-03-12
中文翻译：
增强治疗肝细胞癌的综合治疗传递系统
纳米材料有望用于人类癌症的治疗，但是将多种功能整合到单个药物载体系统中仍然具有挑战性。本文报道了一种基于人丹参B（RhB）末端标记的阳离子聚甲基丙烯酸[2-（二甲氨基）乙基甲基丙烯酸]（PDMAEMA）和疏水性聚（3-叠氮基-2-甲基丙烯酸羟丙酯（PGMA-N 3）装有共价结合的半乳糖的片段。这种具有生物相容性且安全的平台RhB-PDMAEMA25-c-PGMA50-Gal胶束（Gal-胶束）具有四个优点：（1）半乳糖配体通过靶向在HCC细胞系表面过度表达的去唾液酸糖蛋白受体（ASGPR）来增强细胞摄取；（2）RhB末端标记有助于实时成像，以追踪体内和体外；（3）酸性肿瘤微环境使载体系统质子化，从而实现高效药物释放和基因转染；（4）抗癌药阿霉素（DOX）和B细胞淋巴瘤的代码传递2小干扰RNA（Bcl-2 siRNA）协同作用皮下和原位肝癌小鼠模型中的肿瘤生长。这种集成的治疗输送系统具有未来临床HCC治疗的潜力。
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