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A novel redox/pH dual-responsive and hyaluronic acid-decorated multifunctional magnetic complex micelle for targeted gambogic acid delivery for the treatment of triple negative breast cancer.
Drug Delivery ( IF 6.5 ) Pub Date : 2018-10-20 , DOI: 10.1080/10717544.2018.1486472
Mang Mang Sang 1, 2 , Fu Lei Liu 3 , Yang Wang 1, 2 , Ren Jie Luo 1, 2 , Xiao Xian Huan 3 , Ling Fei Han 1, 2 , Zhong Tao Zhang 3 , Feng Feng 3 , Wei Qu 3 , Wenyuan Liu 1, 2 , Feng Zheng 1, 2
Affiliation  

Gambogic acid (GA) is a naturally derived potent anticancer agent with extremely poor biocompatibility. In the present study, a novel of redox/pH dual-responsive multifunctional magnetic complex micelle (sPEG/HA/CSO-SS-Hex/Fe3O4/GA), which consisted of a reducible hexadecanol-modified chitosan oligosaccharide polymer micelle (CSO-SS-Hex) coated with hyaluronic acid (HA) and DCA grafted sheddable PEG-PLL (sPEG) copolymers and loaded with gambogic acid (GA) and Fe3O4 nanoparticles were developed for parenteral delivery for the treatment of triple negative breast cancer (TNBC). The ex vivo study showed that the sPEG shielded cationic HA/CSO-SS-Hex/Fe3O4/GA core at physiological pH but quickly shed off to re-expose the core due to its charge reversible property. The sPEG/HA/CSO-SS-Hex/Fe3O4/GA micelles effectively facilitated tumor-targeted GA delivery by HA, which is a targeting ligand for CD44 receptor of TNBC cells, meanwhile increase GA uptake at the acidic condition but diminished the drug uptake at neutral pH. The in vitro cellular uptake study and in vivo biodistribution and antitumor activity of the formulations were determined, all results showed that the complex micelle enhanced TNBC tumor cellular uptake and fast drug release due to the combined effect of magnet targeting, CD44 receptor-mediated internalization and redox/pH dual-responsive drug release. Hence, tumor-targeted delivery of GA with redox/pH dual-responsive multifunctional magnetic complex micelle sPEG/HA/CSO-SS-Hex/Fe3O4/GA might have potential implications for the chemotherapy of TNBC.

中文翻译:

一种新颖的氧化还原/ pH双响应和透明质酸修饰的多功能磁性复合胶束,可靶向递送藤黄酸,用于治疗三阴性乳腺癌。

藤黄酸(GA)是一种天然衍生的有效抗癌剂,生物相容性极差。在本研究中,一种新型的氧化还原/ pH双响应多功能磁性复合胶束(sPEG / HA / CSO-SS-Hex / Fe3O4 / GA),由可还原的十六烷醇改性的壳聚糖寡糖聚合物胶束(CSO-SS)组成。开发了透明质酸(HA)和DCA接枝的可流挂PEG-PLL(sPEG)共聚物涂层并负载了藤黄酸(GA)和Fe3O4纳米颗粒的β-己二酸,用于肠胃外递送,以治疗三阴性乳腺癌(TNBC)。体外研究表明,sPEG在生理pH值下可屏蔽阳离子HA / CSO-SS-Hex / Fe3O4 / GA核,但由于其电荷可逆性而迅速脱落以重新暴露核。sPEG / HA / CSO-SS-Hex / Fe3O4 / GA胶束有效地促进了HA对肿瘤靶向GA的递送,HA是TNBC细胞CD44受体的靶向配体,同时增加了酸性条件下GA的吸收但降低了药物的吸收在中性pH下。确定了制剂的体外细胞吸收研究以及体内生物分布和抗肿瘤活性,所有结果表明,由于磁靶向,CD44受体介导的内在化和内在结合,复合胶束提高了TNBC肿瘤细胞的吸收和药物的快速释放。氧化还原/ pH双反应药物释放。因此,以氧化还原/ pH双响应多功能磁性复合胶束sPEG / HA / CSO-SS-Hex / Fe3O4 / GA为靶点的GA的传递可能对TNBC的化疗具有潜在的影响。它是TNBC细胞CD44受体的靶向配体,同时在酸性条件下增加了GA的吸收,但在中性pH下减少了药物的吸收。确定了制剂的体外细胞吸收研究以及体内生物分布和抗肿瘤活性,所有结果表明,由于磁靶向,CD44受体介导的内在化和内在结合,复合胶束提高了TNBC肿瘤细胞的吸收和药物的快速释放。氧化还原/ pH双反应药物释放。因此,具有氧化还原/ pH双响应多功能磁性复合胶束sPEG / HA / CSO-SS-Hex / Fe3O4 / GA的GA的肿瘤靶向递送可能对TNBC的化疗有潜在影响。它是TNBC细胞CD44受体的靶向配体,同时在酸性条件下增加了GA的吸收,但在中性pH下减少了药物的吸收。确定了制剂的体外细胞吸收研究以及体内生物分布和抗肿瘤活性,所有结果表明,由于磁靶向,CD44受体介导的内在化和内在结合,复合胶束提高了TNBC肿瘤细胞的吸收和药物的快速释放。氧化还原/ pH双反应药物释放。因此,以氧化还原/ pH双响应多功能磁性复合胶束sPEG / HA / CSO-SS-Hex / Fe3O4 / GA为靶点的GA的传递可能对TNBC的化疗具有潜在的影响。确定了制剂的体外细胞吸收研究以及体内生物分布和抗肿瘤活性,所有结果表明,由于磁靶向,CD44受体介导的内在化和内在结合,复合胶束提高了TNBC肿瘤细胞的吸收和药物的快速释放。氧化还原/ pH双反应药物释放。因此,以氧化还原/ pH双响应多功能磁性复合胶束sPEG / HA / CSO-SS-Hex / Fe3O4 / GA为靶点的GA的传递可能对TNBC的化疗具有潜在的影响。确定了制剂的体外细胞吸收研究以及体内生物分布和抗肿瘤活性,所有结果表明,由于磁靶向,CD44受体介导的内在化和内在结合,复合胶束提高了TNBC肿瘤细胞的吸收和药物的快速释放。氧化还原/ pH双反应药物释放。因此,以氧化还原/ pH双响应多功能磁性复合胶束sPEG / HA / CSO-SS-Hex / Fe3O4 / GA为靶点的GA的传递可能对TNBC的化疗具有潜在的影响。CD44受体介导的内在化和氧化还原/ pH双反应药物释放。因此,以氧化还原/ pH双响应多功能磁性复合胶束sPEG / HA / CSO-SS-Hex / Fe3O4 / GA为靶点的GA的传递可能对TNBC的化疗具有潜在的影响。CD44受体介导的内在化和氧化还原/ pH双反应药物释放。因此,具有氧化还原/ pH双响应多功能磁性复合胶束sPEG / HA / CSO-SS-Hex / Fe3O4 / GA的GA的肿瘤靶向递送可能对TNBC的化疗有潜在影响。
更新日期:2018-10-18
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