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载药双靶向氧化石墨烯基分子印迹复合材料及其对癌胚抗原的识别

Drug-loaded dual targeting graphene oxide-based molecularly imprinted composite and recognition of carcino-embryonic antigen.

作者信息

Han Shuang, Teng Fu, Wang Yuan, Su Liqiang, Leng Qiuxue, Jiang Haiyan

机构信息

College of Chemistry and Chemical Engineering, Qiqihar University Qiqihar 161006 China

Heilongjiang Province Qiqihar Ecological Environment Monitoring Center Qiqihar 161005 China.

出版信息

RSC Adv. 2020 Mar 17;10(19):10980-10988. doi: 10.1039/d0ra00574f. eCollection 2020 Mar 16.

Abstract

Despite extensive research on functional graphene oxide for anticancer drug delivery, the sensitivity of traditional protein targeting ligands to the environment limits the practical applications of targeted drug delivery. A unique molecularly imprinted magnetic graphene oxide was used as a novel drug delivery system for the treatment of tumors. Molecularly imprinted polymers (MIPs) synthesized by molecular imprinting technology have the advantages of good stability against chemical and enzymatic attacks, high specificity for a target template, and resistance to harsh environments. In our work, the MIP was used for specificity to tumor cells with carcino-embryonic (CEA) tumor markers as the template, and dopamine as the functional monomer was grafted on boronic acid-functionalized magnetic graphene oxide. The structure of the nanoparticles was optimized and characterized in detail by vibrating sample magnetometry, X-ray diffraction analysis, UV-vis spectroscopy, and flow cytometry. The prepared polymer has magnetic properties, specific recognition to CEA, biocompatibility and pH sensitivity for drug delivery. Cell culture research was carried out on the tumor cells and normal cells. The composites exhibited dual targeting properties that not only magnetically target but also specifically increase the drug cytotoxicity to the tumor cells by selectively binding to CEA. On the basis of these results, this study developed a novel approach for targeting tumor cells for drug delivery without needing to modify the protein ligand.

摘要

尽管对用于抗癌药物递送的功能化氧化石墨烯进行了广泛研究,但传统蛋白质靶向配体对环境的敏感性限制了靶向药物递送的实际应用。一种独特的分子印迹磁性氧化石墨烯被用作治疗肿瘤的新型药物递送系统。通过分子印迹技术合成的分子印迹聚合物(MIPs)具有对化学和酶攻击稳定性好、对目标模板特异性高以及耐恶劣环境的优点。在我们的工作中,以癌胚抗原(CEA)肿瘤标志物为模板,将MIP用于对肿瘤细胞的特异性识别,并将多巴胺作为功能单体接枝到硼酸功能化的磁性氧化石墨烯上。通过振动样品磁强计、X射线衍射分析、紫外可见光谱和流式细胞术对纳米颗粒的结构进行了优化和详细表征。所制备的聚合物具有磁性、对CEA的特异性识别、生物相容性以及用于药物递送的pH敏感性。对肿瘤细胞和正常细胞进行了细胞培养研究。该复合材料表现出双重靶向特性,不仅能磁性靶向,还能通过与CEA选择性结合,特异性地增加对肿瘤细胞的药物细胞毒性。基于这些结果,本研究开发了一种无需修饰蛋白质配体即可靶向肿瘤细胞进行药物递送的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b857/9050445/ff62b9303d63/d0ra00574f-f1.jpg

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