Phospholipid-mimicking cell-penetrating polymers: principles and applications
Phospholipid-mimicking cell-penetrating polymers: principles and applications
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DOI：
10.1039/d0tb01520b
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发表时间：
2020-09-14
影响因子：
7
通讯作者：
Ishihara, Kazuhiko
中科院分区：
文献类型：
--
作者：
Goda, Tatsuro;Miyahara, Yuji;Ishihara, Kazuhiko
了解真核生物细胞膜与纳米材料的相互作用是构建高效、安全的纳米药物和分子生物工程所必需的。通过主动内吞作用的纳米载体的细胞内摄取限制了内体区室的细胞内分布，损害了货物分子的预期生物作用。非内吞细胞内迁移是具有阳离子或两亲性的纳米材料逃避脂质双层质膜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，非内吞内化的合成的两亲性聚合物为基础的纳米聚集体，模仿天然磷脂的结构，可以发生不诱导细胞毒性。使用质子泄漏分析表明，聚合物进入细胞的两亲性诱导的膜融合，而不是通过跨膜孔形成。这些非细胞毒性的细胞穿透聚合物可能会发现在药物输送系统，基因转染，细胞治疗和生物分子工程的应用。
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.