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Progressive slowdown/prevention of cellular senescence by CD9-targeted delivery of rapamycin using lactose-wrapped calcium carbonate nanoparticles

Title
Progressive slowdown/prevention of cellular senescence by CD9-targeted delivery of rapamycin using lactose-wrapped calcium carbonate nanoparticles
Author
최한곤
Keywords
HUMAN-CELLS; SECRETORY PHENOTYPE; CANCER; EXPRESSION; FIBROBLASTS; CD9; SUPPRESSION; CYTOKINES; MOTILITY; CULTURE
Issue Date
2017-04
Publisher
NATURE PUBLISHING GROUP
Citation
SCIENTIFIC REPORTS, v. 7, Article no. 43299, Page. 1-11
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.
URI
https://www.nature.com/articles/srep43299https://repository.hanyang.ac.kr/handle/20.500.11754/71969
ISSN
2045-2322
DOI
10.1038/srep43299
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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