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Molecular bottlebrush with pH-responsive cleavable bonds as a unimolecular vehicle for anticancer drug delivery
Biomaterials Advances ( IF 7.9 ) Pub Date : 2021-09-17 , DOI: 10.1016/j.msec.2021.112439
Wojciech Raj 1 , Krzysztof Jerczynski 1 , Mahdi Rahimi 1 , Agata Przekora 2 , Krzysztof Matyjaszewski 3 , Joanna Pietrasik 1
Affiliation  

Drug delivery systems with targeted and smart properties have emerged as an efficient strategy to overcome the challenges of cancer chemotherapy such as toxic side effects and the development of multidrug resistance. In this study, a biocompatible bottlebrush polymer poly((3-(2-bromo-2-methylpropionate)propyldimethylsilyloxy)ethyl methacrylate)-graft-poly(2-methacryloyloxyethyl phosphorylcholine) P(BIBS-EMA)-g-PMPC with pH-responsive silanol cleavable bond was designed and developed for delivery of doxorubicin. A549 cell line of human lung carcinoma was tested. The synthesized bottlebrush polymer was analyzed and characterized via Fourier transform infrared spectroscopy, FTIR, nuclear magnetic resonance spectroscopy, 1H NMR, gel permeation chromatography, GPC, dynamic laser light scattering, DLS, and static laser light scattering, SLS, techniques. The cleavage process was also precisely studied to confirm the pH-responsiveness of such bottlebrush polymers. In vitro loading and release studies of doxorubicin as a model drug were examined and the results showed a pH-dependent release manner with a twice higher release rate under cancerous tissue conditions compared to standard physiological conditions. MTT cytotoxicity assay was also performed to prove the biocompatibility of the designed polymeric platform on healthy human cells. Due to the presence of bio-inspired poly(2-methacryloyloxyethyl phosphorylcholine) side chains in the prepared bottlebrush polymer, the formed polymer-drug complex could also exhibit effective internalization into tumor cells. These facts further support the potential use of this carrier in drug delivery applications and for further in vivo studies.



中文翻译:

具有 pH 响应性可裂解键的分子瓶刷作为抗癌药物递送的单分子载体

具有靶向和智能特性的药物递送系统已成为克服癌症化疗挑战的有效策略,例如毒副作用和多药耐药性的发展。在这项研究中,生物相容的聚合物瓶刷聚((3-(2-溴-2-甲基丙酸酯)propyldimethylsilyloxy)乙基甲基丙烯酸酯) -接枝-聚(2-丙烯酰氧基乙基磷酰胆碱)P(BIBS-EMA) --PMPC具有pH响应性硅烷醇可裂解键被设计和开发用于递送多柔比星。测试了人肺癌的A549细胞系。合成的瓶刷聚合物通过傅里叶变换红外光谱、FTIR、核磁共振光谱、1H NMR、凝胶渗透色谱、GPC、动态激光散射、DLS 和静态激光散射、SLS 技术。还精确研究了裂解过程,以确认此类瓶刷聚合物的 pH 响应性。对阿霉素作为模型药物的体外加载和释放研究进行了检查,结果显示出一种 pH 依赖性释放方式,与标准生理条件相比,癌组织条件下的释放速率高两倍。还进行了 MTT 细胞毒性试验以证明设计的聚合物平台对健康人类细胞的生物相容性。由于制备的瓶刷聚合物中存在仿生聚(2-甲基丙烯酰氧基乙基磷酰胆碱)侧链,所形成的聚合物-药物复合物也可以有效地内化到肿瘤细胞中。

更新日期:2021-09-24
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