Mimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform

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 ani...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Valentina Palacio-Castañeda, Rik Oude Egberink, Arbaaz Sait, Lea Andrée, Benedetta Maria Sala, Negar Hassani Besheli, Egbert Oosterwijk, Johan Nilvebrant, Sander C. G. Leeuwenburgh, Roland Brock, Wouter P. R. Verdurmen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	drug delivery affibody CAIX gelatin mRNA nanoparticle Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/842f0bdef5604d1ea314bb50f5788322
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:842f0bdef5604d1ea314bb50f5788322
record_format	dspace
spelling	oai:doaj.org-article:842f0bdef5604d1ea314bb50f57883222021-11-25T18:42:16ZMimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform10.3390/pharmaceutics131119441999-4923https://doaj.org/article/842f0bdef5604d1ea314bb50f57883222021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1944https://doaj.org/toc/1999-4923To 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.Valentina Palacio-CastañedaRik Oude EgberinkArbaaz SaitLea AndréeBenedetta Maria SalaNegar Hassani BesheliEgbert OosterwijkJohan NilvebrantSander C. G. LeeuwenburghRoland BrockWouter P. R. VerdurmenMDPI AGarticledrug deliveryaffibodyCAIXgelatinmRNAnanoparticlePharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1944, p 1944 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	drug delivery affibody CAIX gelatin mRNA nanoparticle Pharmacy and materia medica RS1-441
spellingShingle	drug delivery affibody CAIX gelatin mRNA nanoparticle Pharmacy and materia medica RS1-441 Valentina Palacio-Castañeda Rik Oude Egberink Arbaaz Sait Lea Andrée Benedetta Maria Sala Negar Hassani Besheli Egbert Oosterwijk Johan Nilvebrant Sander C. G. Leeuwenburgh Roland Brock Wouter P. R. Verdurmen Mimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform
description	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.
format	article
author	Valentina Palacio-Castañeda Rik Oude Egberink Arbaaz Sait Lea Andrée Benedetta Maria Sala Negar Hassani Besheli Egbert Oosterwijk Johan Nilvebrant Sander C. G. Leeuwenburgh Roland Brock Wouter P. R. Verdurmen
author_facet	Valentina Palacio-Castañeda Rik Oude Egberink Arbaaz Sait Lea Andrée Benedetta Maria Sala Negar Hassani Besheli Egbert Oosterwijk Johan Nilvebrant Sander C. G. Leeuwenburgh Roland Brock Wouter P. R. Verdurmen
author_sort	Valentina Palacio-Castañeda
title	Mimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform
title_short	Mimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform
title_full	Mimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform
title_fullStr	Mimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform
title_full_unstemmed	Mimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform
title_sort	mimicking the biology of engineered protein and mrna nanoparticle delivery using a versatile microfluidic platform
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/842f0bdef5604d1ea314bb50f5788322
work_keys_str_mv	AT valentinapalaciocastaneda mimickingthebiologyofengineeredproteinandmrnananoparticledeliveryusingaversatilemicrofluidicplatform AT rikoudeegberink mimickingthebiologyofengineeredproteinandmrnananoparticledeliveryusingaversatilemicrofluidicplatform AT arbaazsait mimickingthebiologyofengineeredproteinandmrnananoparticledeliveryusingaversatilemicrofluidicplatform AT leaandree mimickingthebiologyofengineeredproteinandmrnananoparticledeliveryusingaversatilemicrofluidicplatform AT benedettamariasala mimickingthebiologyofengineeredproteinandmrnananoparticledeliveryusingaversatilemicrofluidicplatform AT negarhassanibesheli mimickingthebiologyofengineeredproteinandmrnananoparticledeliveryusingaversatilemicrofluidicplatform AT egbertoosterwijk mimickingthebiologyofengineeredproteinandmrnananoparticledeliveryusingaversatilemicrofluidicplatform AT johannilvebrant mimickingthebiologyofengineeredproteinandmrnananoparticledeliveryusingaversatilemicrofluidicplatform AT sandercgleeuwenburgh mimickingthebiologyofengineeredproteinandmrnananoparticledeliveryusingaversatilemicrofluidicplatform AT rolandbrock mimickingthebiologyofengineeredproteinandmrnananoparticledeliveryusingaversatilemicrofluidicplatform AT wouterprverdurmen mimickingthebiologyofengineeredproteinandmrnananoparticledeliveryusingaversatilemicrofluidicplatform
_version_	1718410783953518592

Mimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform

Ejemplares similares