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

• DOI: 10.1038/s41467-018-05061-3
• Publication Date: 2018-06-28T13:15:58Z
• Authors: 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; Huajian Gao
• Keywords: Male; Science; Drug Compounding; Administration, Oral; Mice, Nude; 02 engineering and technology; Article; Permeability; Diffusion; Mice; Hardness; Cell Line, Tumor; Animals; Humans; Drug Carriers; Antibiotics, Antineoplastic; Q; Biological Transport; Hydrogels; Elasticity; Pancreatic Neoplasms; Mucus; Doxorubicin; Nanoparticles; 0210 nano-technology

AbstractTo 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.