Transportan Peptide Stimulates the Nanomaterial Internalization into Mammalian Cells in the Bystander Manner through Macropinocytosis.
Transportan Peptide Stimulates the Nanomaterial Internalization into Mammalian Cells in the Bystander Manner through Macropinocytosis.
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DOI：
10.3390/pharmaceutics13040552
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发表时间：
2021-04-14
期刊：
影响因子：
5.4
通讯作者：
Pang HB
中科院分区：
文献类型：
--
作者：
Li YX;Wei Y;Zhong R;Li L;Pang HB
与细胞穿透肽（CPPs）的共价偶联是促进纳米材料和其他大分子进入细胞的常用策略。虽然有效，但这一策略需要对纳米材料进行化学修饰，这在应用中并不总是需要的。最近对一些阳离子CPPs的研究表明，它们可以通过共同给药（旁观者方式）来刺激纳米颗粒（NPs）的细胞摄取，而不需要化学修饰。在这项研究中，我们研究了其他类别的CPP，发现转运蛋白肽（TP），一种两亲性的CPP，也表现出这种旁观者活动。当共同给药时，TP肽使细胞能够吞噬多种NPs，以及常见的溶质示踪剂，而这些有效载荷很少或根本没有能力自行进入细胞。这一结果在体外和离体实验中都得到了验证，TP肽与共同给药的NPs（旁观者货物）没有物理相互作用。我们进一步探索了TP肽及其旁观者货物的细胞进入机制，并表明它是由受体依赖性的巨噬细胞作用过程介导的。总之，我们的发现提高了对tp辅助细胞进入的理解，并开辟了将这种肽用于纳米材料递送的新途径。
Covalent coupling with cell-penetrating peptides (CPPs) has been a common strategy to facilitate the cell entry of nanomaterial and other macromolecules. Though efficient, this strategy requires chemical modifications on nanomaterials, which is not always desired for their applications. Recent studies on a few cationic CPPs have revealed that they can stimulate the cellular uptake of nanoparticles (NPs) simply via co-administration (bystander manner), which bypasses the requirement of chemical modification. In this study, we investigated the other classes of CPPs and discovered that transportan (TP) peptide, an amphiphilic CPP, also exhibited such bystander activities. When simply co-administered, TP peptide enabled the cells to engulf a variety of NPs, as well as common solute tracers, while these payloads had little or no ability to enter the cells by themselves. This result was validated in vitro and ex vivo, and TP peptide showed no physical interaction with co-administered NPs (bystander cargo). We further explored the cell entry mechanism for TP peptide and its bystander cargo, and showed that it was mediated by a receptor-dependent macropinocytosis process. Together, our findings improve the understanding of TP-assisted cell entry, and open up a new avenue to apply this peptide for nanomaterial delivery.
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影响因子：
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