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RAFT聚合介导的聚乙二醇甲基丙烯酸酯-硬脂酸嵌段共聚物核壳超分子组装用于高效抗癌药物递送

RAFT polymerization mediated core-shell supramolecular assembly of PEGMA--stearic acid block co-polymer for efficient anticancer drug delivery.

作者信息

Sarkar Priyatosh, Ghosh Santanu, Saha Rima, Sarkar Kishor

机构信息

Gene Therapy and Tissue Engineering Lab, Department of Polymer Science and Technology, University of Calcutta 92, A. P. C. Road Kolkata 700009 India

Department of Materials Engineering, Indian Institute of Science C. V. Raman Avenue Bangalore Karnataka 560012 India.

出版信息

RSC Adv. 2021 May 7;11(28):16913-16923. doi: 10.1039/d1ra01660a. eCollection 2021 May 6.

Abstract

In this work, core-shell supramolecular assembly polymeric nano-architectures containing hydrophilic and hydrophobic segments were synthesized reversible addition fragmentation chain transfer (RAFT) polymerization. Herein, polyethylene glycol methyl ether methacrylate (PEGMA), and stearic acid were used to synthesize the poly(PEGMA) homopolymer and stearyl ethyl methacrylate (SEMA), respectively. Then, PEGMA and SEMA were polymerized through controlled RAFT polymerization to obtain the final diblock copolymer, poly(PEGMA--SEMA) (BCP). Model anticancer drug, doxorubicin (DOX) was loaded on BCPs. Interestingly, efficient DOX release was observed at acidic pH, similar to the cancerous environment pH level. Significant cellular uptake of DOX loaded BCP50 (BCP50-DOX) was observed in MDA-MB-231 triple negative breast cancer cells and resulted in a 35 fold increase in anticancer activity against MDA MB-231 cells compared to free DOX. Scanning electron microscopy (SEM) imaging confirmed the apoptosis mediated cellular death. These core-shell supramolecular assembly polymeric nano-architectures may be an efficient anti-cancer drug delivery system in the future.

摘要

在这项工作中,通过可逆加成-断裂链转移(RAFT)聚合反应合成了包含亲水和疏水链段的核壳超分子组装聚合物纳米结构。在此,分别使用聚乙二醇甲基醚甲基丙烯酸酯(PEGMA)和硬脂酸来合成聚(PEGMA)均聚物和甲基丙烯酸硬脂酰乙酯(SEMA)。然后,通过可控的RAFT聚合反应使PEGMA和SEMA聚合,以获得最终的二嵌段共聚物聚(PEGMA-SEMA)(BCP)。将模型抗癌药物阿霉素(DOX)负载到BCP上。有趣的是,在酸性pH值下观察到了高效的DOX释放,这与癌环境的pH水平相似。在MDA-MB-231三阴性乳腺癌细胞中观察到负载DOX的BCP50(BCP50-DOX)有显著的细胞摄取,并且与游离DOX相比,对MDA-MB-231细胞的抗癌活性增加了35倍。扫描电子显微镜(SEM)成像证实了凋亡介导的细胞死亡。这些核壳超分子组装聚合物纳米结构未来可能是一种高效的抗癌药物递送系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a997/9031514/2dd75bed34f4/d1ra01660a-f1.jpg

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