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Phospholipid-mimicking cell-penetrating polymers: principles and applications.
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-07-21 , DOI: 10.1039/d0tb01520b
Tatsuro Goda 1 , Yuji Miyahara , Kazuhiko Ishihara
Affiliation  

Understanding the interactions of eukaryotic cellular membranes with nanomaterials is required to construct efficient and safe nanomedicines and molecular bioengineering. Intracellular uptake of nanocarriers by active endocytosis limits the intracellular distribution to the endosomal compartment, impairing the intended biological actions of the cargo molecules. Nonendocytic intracellular migration is another route for nanomaterials with cationic or amphiphilic properties to evade the barrier function of the lipid bilayer plasma membranes. Direct transport of nanomaterials into cells is efficient, but this may cause cytotoxic or biocidal effects by temporarily disrupting the biological membrane barrier. We have recently discovered that nonendocytic internalization of synthetic amphipathic polymer-based nanoaggregates that mimic the structure of natural phospholipids can occur without inducing cytotoxicity. Analysis using a proton leakage assay indicated that the polymer enters cells by amphiphilicity-induced membrane fusion rather than by transmembrane pore formation. These noncytotoxic cell-penetrating polymers may find applications in drug delivery systems, gene transfection, cell therapies, and biomolecular engineering.

中文翻译:

磷脂模拟细胞穿透聚合物:原理和应用。

需要了解真核细胞膜与纳米材料的相互作用,以构建有效和安全的纳米药物和分子生物工程。主动内吞作用对纳米载体的细胞内吸收限制了细胞内向内体区室的分布,从而损害了货物分子的预期生物学作用。非内吞性细胞内迁移是具有阳离子或两亲性质的纳米材料逃避脂质双层质膜的屏障功能的另一种途径。将纳米材料直接运输到细胞中是有效的,但是这可能通过暂时破坏生物膜屏障而​​引起细胞毒性或杀生物作用。我们最近发现,在不诱导细胞毒性的情况下,可以发生合成天然两亲性基于聚合物的,模仿天然磷脂结构的纳米聚集体的非内吞内化作用。使用质子泄漏测定的分析表明,聚合物通过两亲性诱导的膜融合而不是通过跨膜孔形成进入细胞。这些无细胞毒性的细胞穿透聚合物可能会在药物递送系统,基因转染,细胞疗法和生物分子工程学中得到应用。
更新日期:2020-09-02
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