TY - JOUR
T1 - SPIONs' Enhancer Effect on Cell Transfection
T2 - An Unexpected Advantage for an Improved Gene Delivery System
AU - Balcells, Laura
AU - Fornaguera, Cristina
AU - Brugada-Vilà, Pau
AU - Guerra-Rebollo, Marta
AU - Meca-Cortés, Óscar
AU - Martínez, Gema
AU - Rubio, Núria
AU - Blanco, Jerónimo
AU - Santamaría, Jesús
AU - Cascante, Anna
AU - Borrós, Salvador
N1 - Funding Information:
Financial supports from MINECO/FEDER (grants RTC-2015-3751-1, SAF2015-64927-C2-1-R, and SAF2015-64927-C2-2-R) and Instituto de Salud Carlos III (Red Tematicá de Investigacioń Cooperativa en Terapia Celular-TERCEL and TRANSMAG transference project from CIBER-BBN) are acknowledged. CIBER-BBN is an initiative funded by the VI National R&D&I Plan2008−2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. L.B. is grateful to IQS for their Predoctoral Grant (Ajuts IQS pels Estudis de Doctrorat). C.F. is grateful to MINECO for their Postdoctoral Fellowship (grant Torres Quevedo 2015). The Support of Ageǹcia de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) from Generalitat de Catalunya is acknowledged for their support through SGR 2014 1170 grant.
Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019/2/6
Y1 - 2019/2/6
N2 - The clinical implantation of gene therapy is hindered by the limitations of current gene delivery vectors, namely, safety issues regarding viral vectors and low transfection efficacy regarding nonviral vectors. Thus, the design of safe and efficient gene carriers is a key point for the success of such therapies. In addition, when employing genetically modified cells for further applications, the selection of successfully modified cells becomes crucial. To address these issues, we have developed multicomponent nanoparticles composed of poly(ß-amino ester) (pBAE) polymers, plasmid DNA, and superparamagnetic iron oxide nanoparticles (SPIONs). Whereas pBAEs were initially employed as safe and biocompatible carriers with improved transfection efficiency, as compared to commercial vectors, SPIONs were used because of their magnetic character that enables cell selection. Surprisingly, the results presented here revealed an unexpected enhancer effect of SPIONs on the transfection efficiency of pBAE/pDNA polyplexes in both permissive and reluctant to transfection cell lines. This unanticipated outcome, together with the allowance to perform a selective magnetic sorting of genetically modified cells without interfering in cell transfection, opens the door to SPION-containing nanoparticles as promising tools for cell therapy approaches.
AB - The clinical implantation of gene therapy is hindered by the limitations of current gene delivery vectors, namely, safety issues regarding viral vectors and low transfection efficacy regarding nonviral vectors. Thus, the design of safe and efficient gene carriers is a key point for the success of such therapies. In addition, when employing genetically modified cells for further applications, the selection of successfully modified cells becomes crucial. To address these issues, we have developed multicomponent nanoparticles composed of poly(ß-amino ester) (pBAE) polymers, plasmid DNA, and superparamagnetic iron oxide nanoparticles (SPIONs). Whereas pBAEs were initially employed as safe and biocompatible carriers with improved transfection efficiency, as compared to commercial vectors, SPIONs were used because of their magnetic character that enables cell selection. Surprisingly, the results presented here revealed an unexpected enhancer effect of SPIONs on the transfection efficiency of pBAE/pDNA polyplexes in both permissive and reluctant to transfection cell lines. This unanticipated outcome, together with the allowance to perform a selective magnetic sorting of genetically modified cells without interfering in cell transfection, opens the door to SPION-containing nanoparticles as promising tools for cell therapy approaches.
KW - Poly(beta-amino ester)s
KW - Magnetic nanoparticles
KW - Gold nanoparticles
KW - Nonviral vectors
KW - Dna delivery
KW - In-vivo
KW - Therapy
KW - Sirna
KW - Efficient
KW - Polyelectrolytes
UR - https://www.scopus.com/pages/publications/85061210590
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000460237300030&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1021/acsomega.8b02905
DO - 10.1021/acsomega.8b02905
M3 - Article
AN - SCOPUS:85061210590
SN - 2470-1343
VL - 4
SP - 2728
EP - 2740
JO - ACS Omega
JF - ACS Omega
IS - 2
ER -