期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 1-11出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep43299
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资金
- National Research Foundation of Korea (NRF) - Korea government (MSIP) [2015R1A2A2A01004118, 2015R1A2A2A04004806]
- Medical Research Center Program through the NRF - MSIP [2015R1A5A2009124]
- National Research Foundation of Korea [22A20154413174, 2015R1A5A2009124, 2015R1A2A2A04004806] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Cellular senescence, a state of irreversible growth arrest and altered cell function, causes aging-related diseases. Hence, treatment modalities that could target aging cells would provide a robust therapeutic avenue. Herein, for the first time, we utilized CD9 receptors (overexpressed in senescent cells) for nanoparticle targeting in addition to the inherent beta-galactosidase activity. In our study, CD9 monoclonal antibody-conjugated lactose-wrapped calcium carbonate nanoparticles loaded with rapamycin (CD9-Lac/CaCO3/Rapa) were prepared for targeted rapamycin delivery to senescent cells. The nanoparticles exhibited an appropriate particle size (similar to 130 nm) with high drug-loading capacity (similar to 20%). In vitro drug release was enhanced in the presence of beta-galactosidase suggesting potential cargo drug delivery to the senescent cells. Furthermore, CD9-Lac/CaCO3/Rapa exhibited high uptake and anti-senescence effects (reduced beta-galactosidase and p53/p21/CD9/cyclin D1 expression, reduced population doubling time, enhanced cell proliferation and migration, and prevention of cell cycle arrest) in old human dermal fibroblasts. Importantly, CD9-Lac/CaCO3/Rapa significantly improved the proliferation capability of old cells as suggested by BrdU staining along with significant reductions in senescence-associated secretory phenotypes (IL-6 and IL-1 beta) (P < 0.05). Altogether, our findings suggest the potential applicability of CD9-Lac/CaCO3/Rapa in targeted treatment of senescence.
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