RT Journal Article
T1 Zebrafish as a platform to evaluate the potential of lipidic nanoemulsions for gene therapy in cancer
A1 Cascallar, María
A1 Lores, Saínza
A1 Pensado López, Alba
A1 Quelle Regaldie, Ana
A1 Sánchez Piñón, Laura
A1 Piñeiro, Roberto
A1 Hurtado, Pablo
A1 Fuente Freire, María de la
K1 Cancer
K1 Gene therapy
K1 miRNA
K1 Nanomedicine
K1 Pharmacology  plasmid
K1 Zebrafish
AB Gene therapy is a promising therapeutic approach that has experienced significant groth in recent decades, with gene nanomedicines reaching the clinics. However, it is still necessary to continue developing novel vectors able to carry, protect, and release the nucleic acids into the target cells, to respond to the widespread demand for new gene therapies to address current unmet clinical needs. We propose here the use of zebrafish embryos as an in vivo platform to evaluate the potential of newly developed nanosystems for gene therapy applications in cancer treatment. Zebrafish embryos have several advantages such as low maintenance costs, transparency, robustness, and a high homology with the human genome. In this work, a new type of putrescine-sphingomyelin nanosystems (PSN), specifically designed for cancer gene therapy applications, was successfully characterized and demonstrated its potential for delivery of plasmid DNA (pDNA) and miRNA (miR). On one hand, we were able to validate a regulatory effect of the PSN/miR on gene expression after injection in embryos of 0 hpf. Additionally, experiments proved the potential of the model to study the transport of the associated nucleic acids (pDNA and miR) upon incubation in zebrafish water. The biodistribution of PSN/pDNA and PSN/miR in vivo was also assessed after microinjection into the zebrafish vasculature, demonstrating that the nucleic acids remained associated with the PSN in an in vivo environment, and could successfully reach disseminated cancer cells in zebrafish xenografts. Altogether, these results demonstrate the potential of zebrafish as an in vivo model to evaluate nanotechnology-based gene therapies for cancer treatment, as well as the capacity of the developed versatile PSN formulation for gene therapy applications
PB Frontiers
YR 2022
FD 2022
LK http://hdl.handle.net/10347/32171
UL http://hdl.handle.net/10347/32171
LA eng
NO Cascallar, M., Hurtado, P., Lores, S., Pensado-López, A., Quelle-Regaldie, A., Sánchez, L., ... & de la Fuente, M. (2022). Zebrafish as a platform to evaluate the potential of lipidic nanoemulsions for gene therapy in cancer. Frontiers in Pharmacology, 13. DOI 10.3389/fphar.2022.1007018
NO This research was funded by the Instituto de Salud Carlos IIIISCIII and the European Regional Development Fund (FEDER) (AC18/00107, AC18/00045, PI18/00176); by the ERA-NET EURONANOMED III project METASTARG (Grant Number JTC 2018-045) and the ERA-NET EURONANOMED III project PANIPAC (Grant Number JTC 2018/041); and by Axencia Galega de Innovación (GAIN), Consellería de Economía, Emprego e Industria (IN607B2021/14). RP was supported by Roche-Chus Joint Unit (IN853B 2018/03) funded by Axencia Galega de Innovación (GAIN), Consellería de Economía, Emprego e Industria. SL, PH, and AP-L. were funded by a Predoctoral fellowship (IN606A-2019/003, IN606A-2018/019 and ED481A-2018/095) from Axencia Galega de Innovación (GAIN, Xunta de Galicia).
DS Minerva
RD 9 jun 2026