Cell‐Penetrating Peptide‐Conjugated Polymer Micelle for pDNA/siRNA Delivery
Cell‐Penetrating Peptide‐Conjugated Polymer Micelle for pDNA/siRNA Delivery
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用于 pDNA/siRNA 递送的细胞穿透肽缀合聚合物胶束
DOI：
10.1002/9783527835997.ch16
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Takanori Kanazawa
中科院分区：
文献类型：
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作者：
Kurano Takumi;Kanazawa Takanori;Iioka Shingo;Kondo Hiromu;Kosuge Yasuhiro;Suzuki Toyofumi;Takanori Kanazawa
细胞穿透肽(CPPs)可以增强细胞内对蛋白质和基因/核酸等大分子的摄取。许多含有碱性氨基酸的CPP，特别是低聚精氨酸，对于膜的通透性是必不可少的。质粒DNA(PDNA)/小干扰RNA(SiRNA)在内化进入细胞后，能够从内体逃逸到细胞质中，并从细胞质中的CpP释放出来，从而实现高效的基因表达/RNA干扰，这是非常重要的。通过嵌段共聚物的多分子组装形成的聚合物胶束可用于药物和PDNA/siRNAs的核壳型胶体载体。特别是，通过在递送系统上涂覆生物惰性水相容聚合物(如聚乙二醇)来延长循环时间是可能的，这可以引起递送载体的空间稳定性，防止不必要的聚集和与周围环境的非特异性静电相互作用。在本章中，介绍了CPP-共轭聚合物胶束，它可以通过聚合物胶束调节药物动力学和通过CPP调节细胞内动力学，用于全身、鼻到脑、口服给药，以实现对肿瘤、炎症和脑组织的PDNA/siRNA递送系统。
The intracellular uptake of macromolecules, such as proteins and genes/nucleic acids, can be enhanced by cell‐penetrating peptides (CPPs). A lot of CPPs with basic amino acids, in particular, oligoarginine, are essential for membrane permeability. After internalization into the cell, it is very important that plasmid DNA (pDNA)/small interfering RNA (siRNA) could be escaped from the endosome into the cytoplasm and released from the CPPs in the cytoplasm to achieve efficient gene expression/RNA interfering. The polymeric micelles formed through the multimolecular assembly of the block copolymer can then be utilized for core‐shell type colloidal carriers for drugs and pDNA/siRNAs. In particular, it is possible to enhance the circulation time by coating the delivery system with bioinert water‐compatible polymers such as poly(ethylene glycol) (PEG), which can give rise to steric stabilization of the delivery vehicle against undesirable aggregation and nonspecific electrostatic interactions with the surroundings.In this chapter, CPP‐conjugated polymer micelles, which can regulate both pharmacokinetics by polymer micelles and intracellular dynamics by CPP for systemic, nose‐to‐brain, oral delivery to achieve pDNA/siRNA delivery system to tumor, inflamed, and brain tissue, were introduced.