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使用拟肽缀合自组装纳米颗粒进行靶向递送。

Targeted delivery with peptidomimetic conjugated self-assembled nanoparticles.

作者信息

Jabbari Esmaiel

机构信息

Biomimetic Materials and Tissue Engineering Laboratory, Department of Chemical Engineering, University of South Carolina, Columbia, South Carolina, 29208, USA.

出版信息

Pharm Res. 2009 Mar;26(3):612-30. doi: 10.1007/s11095-008-9802-1. Epub 2008 Dec 17.

Abstract

Peptides produce specific nanostructures, making them useful for targeting in biological systems but they have low bioavailability, potential immunogenicity and poor metabolic stability. Peptidomimetic self-assembled NPs can possess biological recognition motifs as well as providing desired engineering properties. Inorganic NPs, coated with self-assembled macromers for stability and anti-fouling, and conjugated with target-specific ligands, are advancing imaging from the anatomy-based level to the molecular level. Ligand conjugated NPs are attractive for cell-selective tumor drug delivery, since this process has high transport capacity as well as ligand dependent cell specificity. Peptidomimetic NPs can provide stronger interaction with surface receptors on tumor cells, resulting in higher uptake and reduced drug resistance. Self-assembled NPs conjugated with peptidomimetic antigens are ideal for sustained presentation of vaccine antigens to dendritic cells and subsequent activation of T cell mediated adaptive immune response. Self-assembled NPs are a viable alternative to encapsulation for sustained delivery of proteins in tissue engineering. Cell penetrating peptides conjugated to NPs are used as intracellular delivery vectors for gene expression and as transfection agents for plasmid delivery. In this work, synthesis, characterization, properties, immunogenicity, and medical applications of peptidomimetic NPs in imaging, tumor delivery, vaccination, tissue engineering, and intracellular delivery are reviewed.

摘要

肽可产生特定的纳米结构,使其在生物系统靶向方面很有用,但它们的生物利用度低、具有潜在免疫原性且代谢稳定性差。拟肽自组装纳米颗粒可拥有生物识别基序,并具备所需的工程特性。无机纳米颗粒通过自组装大分子进行包覆以实现稳定性和抗污性能,并与靶向特异性配体偶联,正推动成像从基于解剖学的层面发展到分子层面。配体偶联纳米颗粒对细胞选择性肿瘤药物递送具有吸引力,因为这一过程具有高运输能力以及配体依赖性细胞特异性。拟肽纳米颗粒可与肿瘤细胞表面受体产生更强的相互作用,从而实现更高的摄取率并降低耐药性。与拟肽抗原偶联的自组装纳米颗粒非常适合将疫苗抗原持续呈递给树突状细胞,并随后激活T细胞介导的适应性免疫反应。自组装纳米颗粒是组织工程中用于蛋白质持续递送的封装的可行替代方案。与纳米颗粒偶联的细胞穿透肽用作基因表达的细胞内递送载体以及质粒递送的转染剂。在这项工作中,对拟肽纳米颗粒在成像、肿瘤递送、疫苗接种、组织工程和细胞内递送方面的合成、表征、性质、免疫原性及医学应用进行了综述。

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