The Different Cellular Entry Routes for Drug Delivery Using Cell Penetrating Peptides

IF 2.4 4区 生物学 Q4 CELL BIOLOGY
Michael Okafor, David Schmitt, Stéphane Ory, Stéphane Gasman, Christelle Hureau, Peter Faller, Nicolas Vitale
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Abstract

The cell plasma membrane acts as a semi-permeable barrier essential for cellular protection and function, posing a challenge for therapeutic molecule delivery. Conventional techniques for crossing this barrier, including biophysical and biochemical methods, often exhibit limitations such as cytotoxicity and the risk of genomic integration when viral vectors are involved. In contrast, cell-penetrating peptides (CPPs) offer a promising non-invasive means to deliver a broad range of molecular cargoes, including proteins, nucleic acids and small molecules, into cells. CPPs, typically 5 to 30 amino acids long and rich in basic or non-polar residues, interact favourably with different cell membranes. These peptides have evolved since the discovery of the HIV-1 TAT peptide in the 1980s, expanding into various CPP families with diverse therapeutic applications. CPPs can form covalent or non-covalent complexes with their cargo, influencing their stability and efficacy. Based on their sequence properties and interactions, CPPs can be amphipathic or non-amphipathic, with distinct mechanisms of membrane penetration, such as direct penetration and endocytosis. While their uptake mechanisms are complex and not fully elucidated, ongoing optimization aims to enhance CPP specificity and efficacy. CPPs have demonstrated potential in drug delivery, gene therapy, cancer treatment and vaccine development, addressing key safety and efficiency concerns associated with viral vectors. This review explores the classification, mechanisms of action and therapeutic potential. It focuses on the intracellular vesicular trafficking of CPPs, highlighting their role as transformative tools in advancing cellular therapies and medical treatments.

Abstract Image

利用细胞穿透肽给药的不同细胞进入途径
细胞膜作为细胞保护和功能所必需的半透性屏障,对治疗性分子递送提出了挑战。跨越这一屏障的传统技术,包括生物物理和生化方法,往往表现出局限性,如细胞毒性和涉及病毒载体时基因组整合的风险。相比之下,细胞穿透肽(CPPs)提供了一种有前途的非侵入性手段,可以将包括蛋白质、核酸和小分子在内的广泛分子货物输送到细胞中。CPPs通常有5到30个氨基酸长,富含碱性或非极性残基,与不同的细胞膜有利地相互作用。自20世纪80年代发现HIV-1 TAT肽以来,这些肽已经进化,扩展到具有不同治疗应用的各种CPP家族。CPPs可与载物形成共价或非共价复合物,影响其稳定性和疗效。基于它们的序列性质和相互作用,CPPs可以是两亲性的或非两亲性的,具有不同的透膜机制,如直接透膜和内吞作用。虽然它们的摄取机制复杂且尚未完全阐明,但正在进行的优化旨在提高CPP的特异性和有效性。CPPs已显示出在药物递送、基因治疗、癌症治疗和疫苗开发方面的潜力,解决了与病毒载体相关的关键安全性和效率问题。本文就其分类、作用机制及治疗潜力作一综述。它侧重于CPPs的细胞内囊泡运输,强调它们在推进细胞疗法和医学治疗方面作为变革性工具的作用。
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来源期刊
Biology of the Cell
Biology of the Cell 生物-细胞生物学
CiteScore
5.30
自引率
0.00%
发文量
53
审稿时长
>12 weeks
期刊介绍: The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms. This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.
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