Rapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers

doi:10.1038/s41467-018-05061-3

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物制剂研究中心

	Rapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers
	Yu, Miaorong 2,5; Xu, Lu 3; Tian, Falin 4; Su, Qian 2,4,6; Zheng, Nan 3; Yang, Yiwei 2,5; Wang, Jiuling 2,4,6; Wang, Aohua 2,5; Zhu, Chunliu5 ; Guo, Shiyan 5
刊名	NATURE COMMUNICATIONS
	2018-07-04
卷号	9
ISSN号	2041-1723
DOI	10.1038/s41467-018-05061-3
文献子类	Article
英文摘要	To optimally penetrate biological hydrogels such as mucus and the tumor interstitial matrix, nanoparticles (NPs) require physicochemical properties that would typically preclude cellular uptake, resulting in inefficient drug delivery. Here, we demonstrate that (poly(lactic-co-glycolic acid) (PLGA) core)-(lipid shell) NPs with moderate rigidity display enhanced diffusivity through mucus compared with some synthetic mucus penetration particles (MPPs), achieving a mucosal and tumor penetrating capability superior to that of both their soft and hard counterparts. Orally administered semi-elastic NPs efficiently overcome multiple intestinal barriers, and result in increased bioavailability of doxorubicin (Dox) (up to 8 fold) compared to Dox solution. Molecular dynamics simulations and super-resolution microscopy reveal that the semi-elastic NPs deform into ellipsoids, which enables rotation-facilitated penetration. In contrast, rigid NPs cannot deform, and overly soft NPs are impeded by interactions with the hydrogel network. Modifying particle rigidity may improve the efficacy of NP-based drugs, and can be applicable to other barriers.
资助项目	National Natural Science Foundation of China[81373356] ; National Natural Science Foundation of China[81573378] ; National Natural Science Foundation of China[81773651] ; National Natural Science Foundation of China[11422215] ; National Natural Science Foundation of China[11272327] ; National Natural Science Foundation of China[11672079] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDA01020304] ; National Science Foundation[CMMI-1562904] ; K.C. Wong Education Foundation[CASIMM0120153020] ; New Star Program, Shanghai Institute of Materia Medica, CAS[00000000] ; State Key Laboratory of Nonlinear Mechanics[00000000]
WOS关键词	ORAL INSULIN DELIVERY ; GASTROINTESTINAL MUCUS ; DRUG-DELIVERY ; HYBRID NANOPARTICLES ; MUCOSAL TISSUES ; EX-VIVO ; DIFFUSION ; PARTICLES ; MICROENVIRONMENT ; ENDOCYTOSIS
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000437252300007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279667]
专题	药物制剂研究中心
通讯作者	Gan, Yong; Shi, Xinghua; Gao, Huajian
作者单位	1.Brown Univ, Sch Engn, Providence, RI 02912 USA 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 3.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Liaoning, Peoples R China; 4.Chinese Acad Sci, Natl Ctr Nanosci & Technol, CAS Ctr Excellence Nanosci, CAS Key Lab Nanosyst & Hierarchy Fabricat, Beijing 100190, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 6.Chinese Acad Sci, Inst Mech, LNM, Beijing 100190, Peoples R China;
推荐引用方式 GB/T 7714	Yu, Miaorong,Xu, Lu,Tian, Falin,et al. Rapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers[J]. NATURE COMMUNICATIONS,2018,9.
APA	Yu, Miaorong.,Xu, Lu.,Tian, Falin.,Su, Qian.,Zheng, Nan.,...&Gao, Huajian.(2018).Rapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers.NATURE COMMUNICATIONS,9.
MLA	Yu, Miaorong,et al."Rapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers".NATURE COMMUNICATIONS 9(2018).