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Mimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform
Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Biochem, Med Ctr, Geert Grootepl 28, NL-6525 GA Nijmegen, Netherlands..ORCID iD: 0000-0001-9314-4000
Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Biochem, Med Ctr, Geert Grootepl 28, NL-6525 GA Nijmegen, Netherlands..
Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Biochem, Med Ctr, Geert Grootepl 28, NL-6525 GA Nijmegen, Netherlands..
Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept DentistryRegenerat Biomat, Med Ctr, Philips Van Leydenlaan 25, NL-6525 EX Nijmegen, Netherlands..ORCID iD: 0000-0002-8097-1127
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2021 (English)In: Pharmaceutics, E-ISSN 1999-4923, Vol. 13, no 11, p. 1944-, article id 1944Article in journal (Refereed) Published
Abstract [en]

To investigate the delivery of next-generation macromolecular drugs, such as engineered proteins and mRNA-containing nanoparticles, there is an increasing push towards the use of physiologically relevant disease models that incorporate human cells and do not face ethical dilemmas associated with animal use. Here, we illustrate the versatility and ease of use of a microfluidic platform for studying drug delivery using high-resolution microscopy in 3D. Using this microfluidic platform, we successfully demonstrate the specific targeting of carbonic anhydrase IX (CAIX) on cells overexpressing the protein in a tumor-mimicking chip system using affibodies, with CAIX-negative cells and non-binding affibodies as controls. Furthermore, we demonstrate this system's feasibility for testing mRNA-containing biomaterials designed to regenerate bone defects. To this end, peptide-and lipid-based mRNA formulations were successfully mixed with colloidal gelatin in microfluidic devices, while translational activity was studied by the expression of a green fluorescent protein. This microfluidic platform enables the testing of mRNA delivery from colloidal biomaterials of relatively high densities, which represents a first important step towards a bone-on-a-chip platform. Collectively, by illustrating the ease of adaptation of our microfluidic platform towards use in distinct applications, we show that our microfluidic chip represents a powerful and flexible way to investigate drug delivery in 3D disease-mimicking culture systems that recapitulate key parameters associated with in vivo drug application.

Place, publisher, year, edition, pages
MDPI AG , 2021. Vol. 13, no 11, p. 1944-, article id 1944
Keywords [en]
drug delivery, affibody, CAIX, gelatin, mRNA, nanoparticle, microfluidics, nanomedicine, biomaterial
National Category
Biochemistry Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:kth:diva-313311DOI: 10.3390/pharmaceutics13111944ISI: 000792960900025PubMedID: 34834361Scopus ID: 2-s2.0-85120710758OAI: oai:DiVA.org:kth-313311DiVA, id: diva2:1663477
Note

QC 20220602

Available from: 2022-06-02 Created: 2022-06-02 Last updated: 2025-02-20Bibliographically approved

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Sala, Benedetta MariaNilvebrant, Johan

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Palacio-Castaneda, ValentinaAndree, LeaSala, Benedetta MariaNilvebrant, JohanVerdurmen, Wouter P. R.
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Protein TechnologyAlbanova VinnExcellence Center for Protein Technology, ProNova
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Pharmaceutics
BiochemistryMolecular BiologyMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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