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基于氧化还原降解聚合物的智能 pH 敏感胶束作为 DOX/GNPs 载体用于控制药物释放和 CT 成像。

Smart pH-sensitive micelles based on redox degradable polymers as DOX/GNPs carriers for controlled drug release and CT imaging.

机构信息

School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, PR China.

School of Bioscience & Bioengineering, South China University of Technology, Guangzhou, 510640, PR China.

出版信息

Colloids Surf B Biointerfaces. 2018 Mar 1;163:29-40. doi: 10.1016/j.colsurfb.2017.12.008. Epub 2017 Dec 8.


DOI:10.1016/j.colsurfb.2017.12.008
PMID:29278801
Abstract

An amphiphilic copolymer poly(ε-caprolactone)-ss-poly(2-(dimethylamino) ethyl methacrylate), PCL-SS-PDMAEMA, was designed and synthesized using ROP and ARGET ATRP methods. Dual stimulus responsive micelles were prepared by the self-assembly of PCL-SS-PDMAEMA. PDMAEMA could respond to acid conditions with protonation, followed by enhanced hydrophilicity and swelling of the micellar shell. In addition, the cleavable joint disulfide bond between the core and shell was disrupted when exposed to an abundance of the reductant reductive glutathione GSH, leading to the disassembly of the micellar structure. The smart response behavior can be used for intracellular controlled drug release in tumor cells. In terms of "theranostics" with higher therapy effect, the tool for tumor imaging and diagnose through computed tomography (CT) was considered with the loading of gold nanoparticles (GNPs). GNPs with good distribution were prepared by means of in situ reduction by PDMAEMA block and stabilized by the micelles. Polymeric micelles were used to load the anticancer drug doxorubicin (DOX) in the hydrophobic core and GNPs in the hydrophilic PDMAEMA shell. Subsequently, the micellar theranostics platform combining chemotherapy and CT diagnose was obtained. The pH- or redox-triggered drug release profiles suggesting that the DOX/GNPs-loaded micelles facilitated controlled release in response to different simulated microenvironments. Cellular uptake study was carried out, indicating that the micelles could be fast internalized within several hours. MTT assay showing significant inhibition against HepG2 and MCF-7 cells for the DOX/GNPs-loaded micelles. Finally, the in vitro CT imaging assay indicated the good CT diagnosis potential of DOX/GNPs-loaded micelles. The micelle simultaneously loaded with DOX and GNPs represent a promising theranostics platform for efficient cancer chemotherapy and diagnosis.

摘要

一种两亲性嵌段共聚物聚(ε-己内酯)-ss-聚(2-二甲氨基乙基甲基丙烯酸酯),PCL-SS-PDMAEMA,是通过 ROP 和ARGET ATRP 方法设计和合成的。通过 PCL-SS-PDMAEMA 的自组装制备了具有双重刺激响应的胶束。PDMAEMA 可以响应酸性条件,通过质子化增加亲水性和胶束壳的溶胀。此外,当暴露于大量还原剂还原型谷胱甘肽 GSH 时,核心和壳之间的可断裂的二硫键被破坏,导致胶束结构的解体。这种智能响应行为可用于肿瘤细胞内的控释药物释放。为了实现更高治疗效果的“治疗学”,考虑了通过计算机断层扫描(CT)进行肿瘤成像和诊断的工具。通过 PDMAEMA 嵌段原位还原和胶束稳定制备了具有良好分布的金纳米颗粒(GNPs)。聚合物胶束用于将抗癌药物阿霉素(DOX)包封在疏水性核心和亲水性 PDMAEMA 壳中。随后,获得了结合化疗和 CT 诊断的胶束治疗学平台。pH 或氧化还原触发的药物释放曲线表明,DOX/GNPs 载药胶束在不同模拟微环境下促进了药物的控制释放。细胞摄取研究表明,胶束可以在数小时内快速内化。MTT 测定显示 DOX/GNPs 载药胶束对 HepG2 和 MCF-7 细胞有显著的抑制作用。最后,体外 CT 成像试验表明 DOX/GNPs 载药胶束具有良好的 CT 诊断潜力。同时载有 DOX 和 GNPs 的胶束为高效癌症化疗和诊断提供了一种有前途的治疗学平台。

相似文献

[1]
Smart pH-sensitive micelles based on redox degradable polymers as DOX/GNPs carriers for controlled drug release and CT imaging.

Colloids Surf B Biointerfaces. 2017-12-8

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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Acta Biomater. 2013-5-10

[9]
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Pharmaceutics. 2020-3-12

[10]
Reduction sensitive hyaluronan-SS-poly(ε-caprolactone) block copolymers as theranostic nanocarriers for tumor diagnosis and treatment.

Mater Sci Eng C Mater Biol Appl. 2018-12-29

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