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Rapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers
Yu MR; Xu L; Tian FL; Su Q; Zheng N; Yang YW; Wang JL(王九令); Wang AH; Zhu CL; Guo SY; Zhang XX; Gan Y; Shi XH(施兴华); Gao HJ

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.

Indexed BySCI
WOS IDWOS:000437252300007
WOS KeywordOral Insulin Delivery ; Gastrointestinal Mucus ; Drug-delivery ; Hybrid Nanoparticles ; Mucosal Tissues ; Ex-vivo ; Diffusion ; Particles ; Microenvironment ; Endocytosis
WOS Research AreaMultidisciplinary Sciences
WOS SubjectScience & Technology - Other Topics
Funding OrganizationNational Natural Science Foundation of China [81373356, 81573378, 81773651, 11422215, 11272327, 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 ; State Key Laboratory of Nonlinear Mechanics
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Cited Times:44[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Affiliation1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
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, Inst Mech, LNM, Beijing 100190, Peoples R China
6.Brown Univ, Sch Engn, Providence, RI 02912 USA
Recommended Citation
GB/T 7714
Yu MR,Xu L,Tian FL,et al. Rapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers[J]. NATURE COMMUNICATIONS,2018,9:2607.
APA Yu MR.,Xu L.,Tian FL.,Su Q.,Zheng N.,...&Gao HJ.(2018).Rapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers.NATURE COMMUNICATIONS,9,2607.
MLA Yu MR,et al."Rapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers".NATURE COMMUNICATIONS 9(2018):2607.
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