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具有双构象聚乙二醇链的类细菌纳米颗粒在生物组织中的快速转运。

Rapid transport of germ-mimetic nanoparticles with dual conformational polyethylene glycol chains in biological tissues.

机构信息

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 501 Haike Road, Shanghai 201203, P. R. China.

University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, P. R. China.

出版信息

Sci Adv. 2020 Feb 7;6(6):eaay9937. doi: 10.1126/sciadv.aay9937. eCollection 2020 Feb.

DOI:10.1126/sciadv.aay9937
PMID:32083187
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7007268/
Abstract

Polyethylene glycols (PEGs) can improve the diffusivity of nanoparticles (NPs) in biological hydrogels, while extended PEG chains severely impede cellular uptake of NPs. Inspired by invasive germs with flagellum-driven mucus-penetrating and fimbriae-mediated epithelium-adhering abilities, we developed germ-mimetic NPs (GMNPs) to overcome multiple barriers in mucosal and tumor tissues. In vitro studies and computational simulations revealed that the tip-specific extended PEG chains on GMNP functioned similarly to flagella, facilitating GMNP diffusion (up to 83.0-fold faster than their counterparts). Meanwhile, the packed PEG chains on the bodies of GMNP mediated strong adhesive interactions with cells similarly to the fimbriae, preserving cellular uptake efficiency. The in vivo results proved the superior tumor permeability and improved oral bioavailability provided by the GMNP (21.9-fold over administration of crystalline drugs). These findings offer useful guidelines for the rational design of NPs by manipulating surface polymer conformation to realize multiple functions and to enhance delivery efficacy.

摘要

聚乙二醇（PEGs）可以提高纳米颗粒（NPs）在生物水凝胶中的扩散性，而延伸的 PEG 链严重阻碍 NPs 被细胞摄取。受具有鞭毛驱动的粘液穿透和菌毛介导的上皮附着能力的侵袭性细菌的启发，我们开发了细菌模拟纳米颗粒（GMNPs）来克服粘膜和肿瘤组织中的多种屏障。体外研究和计算模拟表明，GMNP 上尖端特异性延伸的 PEG 链的功能类似于鞭毛，促进 GMNP 的扩散（比其对应物快 83.0 倍）。同时，GMNP 体上的紧密堆积的 PEG 链与细胞之间具有很强的粘附相互作用，类似于菌毛，保持了细胞摄取效率。体内结果证明了 GMNP 提供的优异的肿瘤通透性和提高的口服生物利用度（与结晶药物相比增加了 21.9 倍）。这些发现为通过操纵表面聚合物构象来实现多种功能和提高递药效果来合理设计 NPs 提供了有用的指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/8aee03120d03/aay9937-F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/ae4d8ac2a7d8/aay9937-F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/033087fc02f5/aay9937-F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/fdb44129c1ee/aay9937-F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/7499a3cc5520/aay9937-F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/acd06997dbd5/aay9937-F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/8aee03120d03/aay9937-F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/ae4d8ac2a7d8/aay9937-F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/033087fc02f5/aay9937-F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/fdb44129c1ee/aay9937-F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/7499a3cc5520/aay9937-F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/acd06997dbd5/aay9937-F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ece/7007268/8aee03120d03/aay9937-F6.jpg

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