Tailored elasticity combined with biomimetic surface promotes nanoparticle transcytosis to overcome mucosal epithelial barrier

Zheng, Yaxian; Xing, Liyun; Chen, Liqiang; Zhou, Rui; Wu, Jiawei; Zhu, Xi; Li, Lian; Xiang, Yucheng; Wu, Ruinan; Zhang, Ling; Huang, Yuan

doi:10.1016/j.biomaterials.2020.120323

Cited by 54 publications

(37 citation statements)

References 52 publications

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“…The mechanical property of NPs is another important factor in determining the endocytosis process, as proved by extensive experimental research [54][55][56]. However, there are often seemly controversial results regarding the effect of NP elasticity.…”

Section: Size and Elasticitymentioning

confidence: 99%

Interplay of Nanoparticle Properties during Endocytosis

Wang

Song

2021

Crystals

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Nanoparticles (NPs) have been widely applied as drug carriers in drug delivery, due to their unique physical and structural properties. To achieve the drug delivery purpose, receptor-mediated endocytosis is a primary explored mechanism to internalize NPs into tumor cells. During the endocytosis process, properties of NPs, including size, shape, and surface functionality, play an important role in determining the final drug delivery efficacy. Many of these NP properties have been extensively explored individually. However, the multiple NP properties naturally interplay with each other in the endocytosis process to determine the internalization efficiency together. Therefore, it is significantly important to understand the interplay of different NP properties to improve the NP’s final delivery efficacy. In this review, we focus on the interplay of NPs properties on the endocytosis process to summarize the relevant experimental observations and physical mechanisms. Particularly, three different aspects are discussed in detail, including the interplay between size and shape; size and elasticity; shape and elasticity. We have summarized the most recent works and highlighted that building up systematic understandings for the complex interplay between NP properties can greatly help a better design of NP platforms for drug delivery.

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Section: Size and Elasticitymentioning

confidence: 99%

Interplay of Nanoparticle Properties during Endocytosis

Wang

Song

2021

Crystals

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“…Especially cylindrical nanoparticles have repeatedly shown potential to match or outperform spherical analogues. [ 14–16 ] In this context, particle stiffness or elasticity is studied to a lesser content; [ 17–19 ] most likely also due to the difficulty of directly measuring and comparing differences in various particles systems. However, in general stiffer/harder nanoparticles exhibit shorter circulation times compared to their softer counterparts, and cells internalize stiffer nanoparticles at faster rates.…”

Section: Introductionmentioning

confidence: 99%

Stiffness‐Dependent Intracellular Location of Cylindrical Polymer Brushes

Niederberger

Pelras

Manni

et al. 2021

Macromol. Rapid Commun.

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Cylindrical polymer brushes (CPBs) are macromolecules with nanoparticle proportions. Their modular synthesis enables tailoring of their chemical composition as well as the dialing‐up of overall dimensions and physicochemical properties. In this study, two rod‐like poly[(ethylene glycol) methyl ether methacrylate] (PEGMA)‐based CPBs with varying stiffness but otherwise comparable features and functionality, are synthesized. Differences in particle stiffness are assessed using small angle neutron scattering (SANS). It is observed that the fate of the two CPBs within cells is distinctly different. Stiffer CPBs seem to gravitate toward the mitochondria, whereas CPBs with reduced stiffness are present in different intracellular vesicles.

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“…When the ratio between gelatin and the glutaraldehyde cross-linker was changed, more rigid 350 nm cationic nanogels were obtained with Young’s modulus in the range from 630 to 3400 kPa . Using zwitterionic poly(carboxybetaine methacrylate), zwitterionic nanogels with an average size of 120–200 nm and an elastic modulus in the range of 180–1350 kPa were synthesized by inverse microemulsion polymerization using a redox-sensitive l -cystine bis(acrylamide) cross-linker or a carboxybetaine DA cross-linker to control blood circulation and biodistribution of the hydrogel nanoparticles . Supersoft PEG hydrogel particles were synthesized from 8-arm-PEG using a bifunctional N -hydroxysuccinimide cross-linker.…”

Section: Approaches To Regulate the Rigidity Of Polymeric Particlesmentioning

confidence: 77%

“…83 Using zwitterionic poly-(carboxybetaine methacrylate), zwitterionic nanogels with an average size of 120−200 nm and an elastic modulus in the range of 180−1350 kPa were synthesized by inverse microemulsion polymerization using a redox-sensitive L-cystine bis(acrylamide) cross-linker 69 or a carboxybetaine DA crosslinker to control blood circulation and biodistribution of the hydrogel nanoparticles. 84 Supersoft PEG hydrogel particles were synthesized from 8-arm-PEG using a bifunctional Nhydroxysuccinimide cross-linker. The particles exhibited an elastic moduli in the range from 0.2 to 3.3 kPa, 30 which is much lower compared to PEG nanoparticles obtained by PRINT technology (7.8−64 kPa) 24 or protein porous particles obtained through templating on sacrificial porous calcium carbonate and cross-linked with glutaraldehyde (∼4 kPa), 85 which is due to the low density of the supersoft PEG nanogels.…”

Section: Approaches To Regulate the Rigidity Of Polymeric Particlesmentioning

confidence: 84%

“…Similarly, rigid (∼25 kPa) mesoporous hydrogel particles of cross-linked poly( l -glutamic acid) synthesized by the mesoporous silica-templated assembly for the delivery of oligonucleotide CpG adjuvant (800 nm) associated more with human plasmacytoid dendritic cells (DCs) than their softer (∼2 kPa) counterparts after a ∼10 h incubation at 37 °C . The increased uptake of rigid polymeric carriers over softer counterparts was also found for zwitterionic nanogels by epithelial cells, hydrogen-bonded multilayer capsules by macrophages, hydrogel poly(allylamine hydrochloride) PAH capsules by smooth muscle cells, composite multilayer capsules by placental cells, nanoliposomal gels by MDA-MB-231 and MCF-7 human breast cancer cells, and block copolymer micelles by A375 tumor cells …”

Section: Particle Rigidity Controls Particle Interactions With Cellsmentioning

confidence: 86%

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Polymeric Particulates of Controlled Rigidity for Biomedical Applications

Kozlovskaya

Dolmat

Kharlampieva

2021

ACS Appl. Polym. Mater.

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The mechanical stiffness of polymer particles is an important parameter that influences particle circulation in the blood and governs cell–particle adhesion, cellular uptake, and biodistribution. This Review highlights the main approaches to produce micro and nanosized polymeric particulates with controlled mechanical responses and their applications in the biomedical field. We discuss how varying mechanical properties of polymeric particles can affect particle interactions with various types of cancer and immune cells, along with particle behavior in the flow. We also analyze the possibilities of regulating particle rigidity by controlling particle shape, a relatively unexplored research area. The main measurement methods to test the mechanical responses of polymeric particulates are also reviewed. Finally, we summarize recent developments toward controlling the mechanical responses of polymeric particulates relevant to biomedical applications and highlight important perspective directions that can advance fundamental and applied research in this area.

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Tailored elasticity combined with biomimetic surface promotes nanoparticle transcytosis to overcome mucosal epithelial barrier

Cited by 54 publications

References 52 publications

Interplay of Nanoparticle Properties during Endocytosis

Interplay of Nanoparticle Properties during Endocytosis

Stiffness‐Dependent Intracellular Location of Cylindrical Polymer Brushes

Polymeric Particulates of Controlled Rigidity for Biomedical Applications

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