A tissue chamber chip for assessing nanoparticle mobility in the extravascular space.
Although a plethora of nanoparticle configurations have been proposed over the past 10 years, the uniform and deep penetration of systemically injected nanomedicines into the diseased tissue stays as a major biological barrier. Here, a 'Tissue Chamber' chip is designed and fabricated to study the ex...
| Publicado en: | Biomedical Microdevices Vol. 21; no. 2 |
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| Autores principales: | , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jun2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=136256486&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 136256486 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 13872176 ODN jtl: Biomedical Microdevices issn: 13872176 maglogo: N pubinfo: dt: Jun2019 vid: 21 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 136256486 10.1007/s10544-019-0398-5 136256486 ppct: 1 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: A tissue chamber chip for assessing nanoparticle mobility in the extravascular space. aug: au: Lusi, Valeria Moore, Thomas L. Laurino, Federica Coclite, Alessandro Perreira, Rui Ferreira, Miguel Rizzuti, Ilaria Palomba, Roberto Zunino, Paolo Duocastella, Marti Mizrahy, Shoshy Peer, Dan Decuzzi, Paolo affil: Laboratory of Nanotechnology for Precision Medicine, Italian Institute of Technology, Via Morego 30, 16163, Genoa, Italy sug: ab: Although a plethora of nanoparticle configurations have been proposed over the past 10 years, the uniform and deep penetration of systemically injected nanomedicines into the diseased tissue stays as a major biological barrier. Here, a 'Tissue Chamber' chip is designed and fabricated to study the extravascular transport of small molecules and nanoparticles. The chamber comprises a collagen slab, deposited within a PDMS mold, and an 800 μm channel for the injection of the working solution. Through fluorescent microscopy, the dynamics of molecules and nanoparticles was estimated within the gel, under different operating conditions. Diffusion coefficients were derived from the analysis of the particle mean square displacements (MSD). For validating the experimental apparatus and the protocol for data analysis, the diffusion D of FITC-Dextran molecules of 4, 40 and 250 kDa was first quantified. As expected, D reduces with the molecular weight of the dextran molecules. The MSD-derived diffusion coefficients were in good agreement with values derived via fluorescence recovery after photobleaching (FRAP), an alternative technique that solely applies to small molecules. Then, the transport of six nanoparticles with similar hydrodynamic diameters (~ 200 nm) and different surface chemistries was quantified. Surface PEGylation was confirmed to favor the diffusion of nanoparticles within the collagen slab, whereas the surface decoration with hyaluronic acid (HA) chains reduced nanoparticle mobility in a way proportional to the HA molecular weight. To assess further the generality of the proposed approach, the diffusion of the six nanoparticles was also tested in freshly excised brain tissue slices. In these ex vivo experiments, the diffusion coefficients were 5-orders of magnitude smaller than for the Tissue Chamber chip. This was mostly ascribed to the lack of a cellular component in the chip. However, the trends documented for PEGylated and HA-coated nanoparticles in vitro were also confirmed ex vivo. This work demonstrates that the Tissue Chamber chip can be employed to effectively and efficiently test the extravascular transport of nanomedicines while minimizing the use of animals. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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