RT Journal Article
T1 Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA
A1 Leiro, Victoria
A1 Garcia, João Pedro
A1 Moreno, Pedro M. D.
A1 Spencer, Ana Patrícia
A1 Fernández Villamarín, Marcos
A1 Riguera Vega, Ricardo
A1 Fernández Megía, Eduardo
A1 Pêgo, Ana Paula
K1 Dendrimers
K1 Degradability
K1 Esters
K1 Gene therapy
K1 siRNA
AB One important drawback of most of the currently used dendrimers for biomedical applications is their high stability under physiological conditions that can result in cytotoxicity or complications induced by the accumulation of non-degradable synthetic materials in the organism. Particularly in the gene therapy field, vector stability can further hinder the intracellular release of the nucleic acid from the dendriplex, consequently leading to low transfection efficiencies. Therefore, biodegradable cationic dendritic structures have been eagerly awaited. However, the development of these dendritic nanocarriers is challenging because of the undesired and/or premature degradation observed during their synthesis and/or application. Here, we report new hybrid-biodegradable, biocompatible, non-toxic, and water-soluble azide-terminated PEG–GATGE dendritic block copolymers, based on a gallic acid (GA) core and triethylene glycol (TG) butanoate arms, incorporating ester bonds (E) at the dendritic arms/shell. Their successful functionalization by “click” chemistry with unprotected alkynated amines allowed complexation and delivery of siRNA. The hydrophobic character of the GATGE building unit confers to these hydrolyzable dendritic bionanomaterials a great ability to complex, protect and mediate the cellular internalization of siRNA. Moreover, the localization of the degradation points at the dendritic periphery, close to the complexed siRNA, was found to be important for nucleic acid release from the nanoparticles, rendering a significant improvement of the transfection efficiency compared to their hydrolytically stable PEG–GATG copolymer counterparts. The present study puts forward these biodegradable PEG–dendritic block copolymers not only as suitable vectors for nucleic acids, but also as new avenues for further developments exploring their use in theranostics
PB Royal Society of Chemistry
SN 2050-750X
YR 2017
FD 2017-07-07
LK http://hdl.handle.net/10347/17001
UL http://hdl.handle.net/10347/17001
LA eng
NO Leiro, V., Garcia, J., Moreno, P., Spencer, A., Fernandez-Villamarin, M., & Riguera, R. et al. (2017). Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA. Journal Of Materials Chemistry B, 5(25), 4901-4917. doi: 10.1039/c7tb00279c
NO The authors would like to acknowledge the FEDER funds through the Programa Operacional Factoresde Competitividade – COMPETE and the Portuguese funds through FCT – Fundação para a Ciência e aTecnologia (PTDC/CTM-NAN/112428/2009 and PTDC/CTM-NAN/3547/2014) that supported thiswork and the FCT / MEC through National Funds and, when applicable, co-financed by the FEDER viathe PT2020 Partnership Agreement under the 4293 Unit I&D. V. Leiro acknowledges the support by FCT (SFRH/BPD/69110/2010) and by the project NORTE-01-0145-FEDER-000012, financed by NortePortugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 PartnershipAgreement, through the European Regional Development Fund (ERDF). P.M.D. Moreno acknowledgesthe support from the Marie Curie Actions of the European Community’s Seventh Framework Program(PIEF-GA-2011-300485) and FCT fellowship (SFRH/BPD/108738/2015). This work was also financiallysupported by the Spanish Government (MINECO: CTQ2012-34790, CTQ2012-33436) and the Xunta deGalicia (CN2011/037)
DS Minerva
RD 24 abr 2026