Innovative niosome screening for efficient gene delivery in senescent primary umbilical cord stroma-derived MSCs.
4 affiliations
- 1CICA - Centro Interdisciplinar de Química e Bioloxía, Universidade da Coruña, A Coruña, Spain.
- 2Departamento de Bioloxía, Facultade de Ciencias, Universidade da Coruña, A Coruña, Spain.
- 3Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Servizo Galego de Saúde (SERGAS), A Coruña, Spain.
- 4Departamento de Medicina, Facultade de Ciencias da Saúde, Universidade da Coruña (UDC), A Coruña, Spain.
Abstract
The potential of senescent cell clearance to extend healthspan and delay the onset of age-related diseases has driven the development of innovative senotherapeutics. Thus, niosome-based gene therapy has emerged as a promising strategy to overcome the off-target limitations of first-generation senolytics, senomorphics, and senoreverts. In the present study, we investigated two new niosome formulations for genetically modifying primary umbilical cord stroma senescent MSCs (UC-MSCs) in a Palbociclib-induced senescent model, using non-senescent UC-MSCs as a control. These niosomes were formulated by fixing the cationic lipid composition (1,2-di-O-octadecenyl-3 trimethylammonium propane, DOTMA, D) and varying the non-ionic surfactants (polysorbate 20, P20, or polysorbate 80, P80) and the helper lipids (chloroquine, CQ, or cholesterol, CH) (DP20CQ and DP80CH, respectively) at two mole ratios (1:2:1 and 1:2:2 for DP20CQ; 1:2:2 and 1:2:4 for DP80CH). Results on transfection revealed that the DP20CQ formulations outperformed those with DP80CH in both UC-MSCs phenotypes from four different donors. Notably, DP20CQ niosomes prepared at 10/1 and 15/1 DOTMA/DNA ratios achieved the highest transgene expression levels in senescent UC-MSCs, surpassing even the commercial reagent Lipofectamine. Further, DP20CQ formulations exhibited adequate physicochemical properties for transfection and promoted a marked endosomal escape, particularly at the DOTMA/DNA ratio 10/1, without compromising cell viability. These findings underscore the value of niosomes as robust gene delivery vehicles for senescent cells in therapeutic antiaging strategies.
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BibTeX
@article{iglesiasfente2026innovative,
title = {{Innovative niosome screening for efficient gene delivery in senescent primary umbilical cord stroma-derived MSCs.}},
author = {Alba Iglesias-Fente and Junquera López-Seijas and María C Arufe and Juan Antonio Fafián-Labora and Ana Rey-Rico},
journal = {Drug delivery},
year = {2026},
month = oct,
doi = {10.1080/10717544.2026.2726650},
url = {https://europepmc.org/article/MED/42845215},
note = {CC BY},
}
RIS
TY - JOUR
TI - Innovative niosome screening for efficient gene delivery in senescent primary umbilical cord stroma-derived MSCs.
AU - Alba Iglesias-Fente
AU - Junquera López-Seijas
AU - María C Arufe
AU - Juan Antonio Fafián-Labora
AU - Ana Rey-Rico
PY - 2026
DA - 2026/10/08
JO - Drug delivery
DO - 10.1080/10717544.2026.2726650
UR - https://europepmc.org/article/MED/42845215
AB - The potential of senescent cell clearance to extend healthspan and delay the onset of age-related diseases has driven the development of innovative senotherapeutics. Thus, niosome-based gene therapy has emerged as a promising strategy to overcome the off-target limitations of first-generation senolytics, senomorphics, and senoreverts. In the present study, we investigated two new niosome formulations for genetically modifying primary umbilical cord stroma senescent MSCs (UC-MSCs) in a Palbociclib-induced senescent model, using non-senescent UC-MSCs as a control. These niosomes were formulated by fixing the cationic lipid composition (1,2-di-O-octadecenyl-3 trimethylammonium propane, DOTMA, D) and varying the non-ionic surfactants (polysorbate 20, P20, or polysorbate 80, P80) and the helper lipids (chloroquine, CQ, or cholesterol, CH) (DP20CQ and DP80CH, respectively) at two mole ratios (1:2:1 and 1:2:2 for DP20CQ; 1:2:2 and 1:2:4 for DP80CH). Results on transfection revealed that the DP20CQ formulations outperformed those with DP80CH in both UC-MSCs phenotypes from four different donors. Notably, DP20CQ niosomes prepared at 10/1 and 15/1 DOTMA/DNA ratios achieved the highest transgene expression levels in senescent UC-MSCs, surpassing even the commercial reagent Lipofectamine. Further, DP20CQ formulations exhibited adequate physicochemical properties for transfection and promoted a marked endosomal escape, particularly at the DOTMA/DNA ratio 10/1, without compromising cell viability. These findings underscore the value of niosomes as robust gene delivery vehicles for senescent cells in therapeutic antiaging strategies.
SN - 1071-7544
SN - 1521-0464
ER -