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氨基酸涂层沸石咪唑酯骨架用于前列腺癌细胞中遗传物质的递送。

Amino Acid-Coated Zeolitic Imidazolate Framework for Delivery of Genetic Material in Prostate Cancer Cell.

机构信息

School of Science, RMIT University, Melbourne, VIC 3000, Australia.

Ian Potter NanoBiosensing Facility, NanoBiotechnology Research Laboratory (NBRL), RMIT University, Melbourne, VIC 3000, Australia.

出版信息

Molecules. 2023 Jun 20;28(12):4875. doi: 10.3390/molecules28124875.

Abstract

Metal-organic frameworks (MOFs) are currently under progressive development as a tool for non-viral biomolecule delivery. Biomolecules such as proteins, lipids, carbohydrates, and nucleic acids can be encapsulated in MOFs for therapeutic purposes. The favorable physicochemical properties of MOFs make them an attractive choice for delivering a wide range of biomolecules including nucleic acids. Herein, a green fluorescence protein (GFP)-expressing plasmid DNA (pDNA) is used as a representative of a biomolecule to encapsulate within a Zn-based metal-organic framework (MOF) called a zeolitic imidazolate framework (ZIF). The synthesized biocomposites are coated with positively charged amino acids (AA) to understand the effect of surface functionalization on the delivery of pDNA to prostate cancer (PC-3) cells. FTIR and zeta potential confirm the successful preparation of positively charged amino acid-functionalized derivatives of pDNA@ZIF (i.e., pDNA@ZIF). Moreover, XRD and SEM data show that the functionalized derivates retain the pristine crystallinity and morphology of pDNA@ZIF. The coated biocomposites provide enhanced uptake of genetic material by PC-3 human prostate cancer cells. The AA-modulated fine-tuning of the surface charge of biocomposites results in better interaction with the cell membrane and enhances cellular uptake. These results suggest that pDNA@ZIF can be a promising alternative tool for non-viral gene delivery.

摘要

金属-有机骨架(MOFs)作为非病毒生物分子传递的工具,目前正在逐步发展。蛋白质、脂质、碳水化合物和核酸等生物分子可以封装在 MOFs 中用于治疗目的。MOFs 的有利物理化学性质使其成为递送包括核酸在内的各种生物分子的有吸引力的选择。在此,使用表达绿色荧光蛋白(GFP)的质粒 DNA(pDNA)作为生物分子的代表,封装在称为沸石咪唑酯骨架(ZIF)的基于锌的金属-有机骨架(MOF)中。合成的生物复合材料用带正电荷的氨基酸(AA)进行涂层,以了解表面功能化对 pDNA 递送至前列腺癌细胞(PC-3)的影响。FTIR 和 zeta 电位证实了成功制备带正电荷的氨基酸功能化 pDNA@ZIF(即 pDNA@ZIF)衍生物。此外,XRD 和 SEM 数据表明,功能化衍生物保留了 pDNA@ZIF 的原始结晶度和形态。涂层生物复合材料通过 PC-3 人前列腺癌细胞提供了对遗传物质的增强摄取。生物复合材料表面电荷的 AA 调节精细调谐导致与细胞膜更好的相互作用并增强细胞摄取。这些结果表明,pDNA@ZIF 可以成为非病毒基因传递的有前途的替代工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f23/10302622/b21f1e8524a4/molecules-28-04875-g001.jpg

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