Applications and Challenges for Use of Cell-Penetrating Peptides as Delivery Vectors for Peptide and Protein Cargos.
Applications and Challenges for Use of Cell-Penetrating Peptides as Delivery Vectors for Peptide and Protein Cargos.
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DOI：
10.3390/ijms17020185
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发表时间：
2016-01-30
影响因子：
5.6
通讯作者：
Mørck Nielsen H
中科院分区：
文献类型：
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作者：
Kristensen M;Birch D;Mørck Nielsen H
肽和蛋白质的亲水性使它们对细胞膜不可渗透。因此，为了成功地递送基于肽和蛋白质的治疗剂穿过质膜或上皮和内皮屏障，必须采用渗透增强策略。细胞穿透肽（CPP）构成了一种有前途的工具，并且已经显示出将肽和蛋白质递送到细胞中以及穿过各种上皮和血脑屏障（BBB）的应用。CPP介导的肽和蛋白质的递送可以通过CPP与货物肽或蛋白质的共价缀合或通过CPP与其货物的简单批量混合获得的物理络合来进行。两种方法各有利弊，哪种方法更好可能与CPP及其货物的理化性质以及给药途径、特异性屏障和靶细胞有关。除了物理屏障之外，当应用基于肽的递送载体（例如CPP）时必须考虑代谢屏障，并且通常采用稳定性增强策略来延长CPP半衰期。CPP易位细胞膜的机制被认为涉及内吞作用和直接易位，但仍被广泛研究和讨论。事实上，多种因素影响负责细胞CPP内化的机制，缺乏敏感的方法检测的CPP，在某些情况下，货物，进一步复杂化的设计和进行结论性的机制研究。
The hydrophilic nature of peptides and proteins renders them impermeable to cell membranes. Thus, in order to successfully deliver peptide and protein-based therapeutics across the plasma membrane or epithelial and endothelial barriers, a permeation enhancing strategy must be employed. Cell-penetrating peptides (CPPs) constitute a promising tool and have shown applications for peptide and protein delivery into cells as well as across various epithelia and the blood-brain barrier (BBB). CPP-mediated delivery of peptides and proteins may be pursued via covalent conjugation of the CPP to the cargo peptide or protein or via physical complexation obtained by simple bulk-mixing of the CPP with its cargo. Both approaches have their pros and cons, and which is the better choice likely relates to the physicochemical properties of the CPP and its cargo as well as the route of administration, the specific barrier and the target cell. Besides the physical barrier, a metabolic barrier must be taken into consideration when applying peptide-based delivery vectors, such as the CPPs, and stability-enhancing strategies are commonly employed to prolong the CPP half-life. The mechanisms by which CPPs translocate cell membranes are believed to involve both endocytosis and direct translocation, but are still widely investigated and discussed. The fact that multiple factors influence the mechanisms responsible for cellular CPP internalization and the lack of sensitive methods for detection of the CPP, and in some cases the cargo, further complicates the design and conduction of conclusive mechanistic studies.