RT Journal Article
T1 Sphingomyelin nanosystems decorated with TSP-1 derived peptide targeting senescent cells
A1 Jatal, Raneem
A1 Mendes Saraiva, Sofia
A1 Vázquez Vázquez, Carlos
A1 Lelievre, Eric
A1 Coqueret, Olivier
A1 López López, Rafael
A1 Fuente Freire, María de la
K1 Cellular senescence
K1 TSP-1
K1 Sphingomyelin nanoemulsions
AB Senescent cells accumulation can contribute to the development of several age-related diseases, including cancer. Targeting and eliminating senescence cells, would allow the development of new therapeutic approaches for the treatment of different diseases. The 4N1Ks peptide, a 10 amino acid peptide derived from TSP1 protein, combines both features by targeting the CD47 receptor present in the surface of senescent cells and demonstrating senolytic activity, thereby representing a new strategy to take into account. Nonetheless, peptide drugs are known for their biopharmaceutical issues, such as low short half-life and tendency to aggregate, which reduces their bioavailability and limits their therapeutic potential. In order to overcome this problem, herein we propose the use of biodegradable and biocompatible sphingomyelin nanosystems (SNs), decorated with this peptide for the targeting of senescent cells. In order to efficiently associate the 4N1Ks peptide to the nanosystems while exposing it on their surface for an effective targeting of senescent cells, the 4N1Ks peptide was chemically conjugated to a PEGylated hydrophobic chain. The resulting SNs-4N1Ks (SNs-Ks), were extensively characterized for their physicochemical properties, by dynamic light scattering, multiple-angle dynamic light scattering, nanoparticle tracking analysis and atomic force microscopy. The SNs-Ks demonstrated suitable features in terms of size (∼100 nm), association efficiency (87.2 ± 6.9%) and stability in different biorelevant media. Cell toxicity experiments in MCF7 cancer cells indicated an improved cytotoxic effect of SNs-Ks, decreasing cancer cells capacity to form colonies, with respect to free peptide, and an improved hemocompatibility. Lastly, senescence escape preliminary experiments demonstrated the improvement of SNs-Ks senolytic activity of in chemotherapy-induced senescence model of breast cancer cells. Therefore, these results demonstrate for the first time the potential of the combination of SNs with 4N1Ks peptide for the development of innovative senolytic therapies to battle cancer
PB Elsevier
YR 2022
FD 2022
LK http://hdl.handle.net/10347/29382
UL http://hdl.handle.net/10347/29382
LA eng
NO International Journal of Pharmaceutics 617 (2022) 121618
NO This work was funded by Instituto de Salud Carlos III (ISCIII) and European Regional Development Fund (FEDER) (PI18/00176), and by the Axencia Galega de Coñecemento en Saúde (GAIN), Xunta de Galicia (IN607B2021/14). NANOMAG group belongs to Galician Competitive Research Group (GRC) (ED431C-2021/16), co-funded by FEDER (EU). R.J. also acknowledges the European financial support in the frame of the NanoFar program, an Erasmus Mundus Joint Doctorate program in nanomedicine and pharmaceutical innovation
DS Minerva
RD 25 abr 2026