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含肽封端金纳米颗粒的非天然氨基酸用于药物递送应用。

Non-natural amino acids containing peptide-capped gold nanoparticles for drug delivery application.

作者信息

Parween Shaheena, Ali Ashraf, Chauhan Virander S

机构信息

International Centre for Genetic Engineering and Biotechnology, New Delhi, India.

出版信息

ACS Appl Mater Interfaces. 2013 Jul 24;5(14):6484-93. doi: 10.1021/am4017973. Epub 2013 Jul 1.

DOI:10.1021/am4017973
PMID:23767970
Abstract

Peptide-based capping agents for gold nanoparticles (GNPs) are possible alternatives for capping and derivatizing GNPs, but suffer from a major disadvantage of sensitivity toward non specific proteases, which may limit their in vivo utility. Using non-natural analogs of natural α-amino acids offer an attractive alternate strategy to circumvent this potential bottleneck in realizing full potential of peptide based capping gents for GNPs for biological applications. Here, we have designed and developed pentapeptides containing non-natural amino acid (α,β-dehydrophenylalanine and α-aminoisobutyric acid) as capping agents for GNPs. All these peptides were able to efficiently cap GNPs and peptide induced aggregation was not observed. Peptide capped GNPs showed minimal cytotoxicity to mammalian cell lines (HeLa and L929) as well as mice spleenocytes. They encapsulated small drug like molecules and peptide capped GNPs entrapping drugs were more efficient in killing HeLa cells compared to the free drug. Therefore, these non-natural amino acid containing peptide-capped GNPs may be further developed as alternate drug delivery vehicles.

摘要

用于金纳米颗粒(GNPs)的基于肽的封端剂是封端和衍生化GNPs的可能替代方案,但存在对非特异性蛋白酶敏感的主要缺点,这可能会限制它们在体内的应用。使用天然α-氨基酸的非天然类似物提供了一种有吸引力的替代策略,以规避在实现基于肽的GNPs封端剂在生物应用中的全部潜力时的这一潜在瓶颈。在此,我们设计并开发了含有非天然氨基酸(α,β-脱氢苯丙氨酸和α-氨基异丁酸)的五肽作为GNPs的封端剂。所有这些肽都能够有效地封端GNPs,并且未观察到肽诱导的聚集。肽封端的GNPs对哺乳动物细胞系(HeLa和L929)以及小鼠脾细胞显示出最小的细胞毒性。它们包封了类似小分子药物,并且与游离药物相比,包封药物的肽封端GNPs在杀死HeLa细胞方面更有效。因此,这些含非天然氨基酸的肽封端GNPs可能会进一步开发成为替代药物递送载体。

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