Progressive slowdown/prevention of cellular senescence by CD9-targeted delivery of rapamycin using lactose-wrapped calcium carbonate nanoparticlesopen access
- Authors
- Thapa, Raj Kumar; Hanh Thuy Nguyen; Jeong, Jee-Heon; Kim, Jae Ryong; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh
- Issue Date
- Apr-2017
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- HUMAN-CELLS; SECRETORY PHENOTYPE; CANCER; EXPRESSION; FIBROBLASTS; CD9; SUPPRESSION; CYTOKINES; MOTILITY; CULTURE
- Citation
- SCIENTIFIC REPORTS, v.7, pp.1 - 11
- Indexed
- SCIE
SCOPUS
- Journal Title
- SCIENTIFIC REPORTS
- Volume
- 7
- Start Page
- 1
- End Page
- 11
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/9987
- DOI
- 10.1038/srep43299
- ISSN
- 2045-2322
- Abstract
- 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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