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

Miaorong Yu, Lu Xu, Falin Tian, Qian Su, Nan Zheng, Yiwei Yang, Jiuling Wang, Aohua Wang, Chunliu Zhu, Shiyan Guo, XinXin Zhang, Yong Gan (), Xinghua Shi () and Huajian Gao ()
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Miaorong Yu: Chinese Academy of Sciences
Lu Xu: Shenyang Pharmaceutical University
Falin Tian: Chinese Academy of Sciences
Qian Su: University of Chinese Academy of Sciences
Nan Zheng: Shenyang Pharmaceutical University
Yiwei Yang: Chinese Academy of Sciences
Jiuling Wang: University of Chinese Academy of Sciences
Aohua Wang: Chinese Academy of Sciences
Chunliu Zhu: Chinese Academy of Sciences
Shiyan Guo: Chinese Academy of Sciences
XinXin Zhang: Chinese Academy of Sciences
Yong Gan: Chinese Academy of Sciences
Xinghua Shi: University of Chinese Academy of Sciences
Huajian Gao: Brown University

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-05061-3

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