期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 133, 期 -, 页码 378-387出版社
ELSEVIER
DOI: 10.1016/j.colsurfb.2015.04.048
关键词
Controlled drug release; Cellular uptake; Temperature-responsiveness; Gold nanoparticles; in vitro anti-inflammatory activity
资金
- European Union (FEDER funds through COMPETE)
- National Funds (FCT, Fundacao para a Ciencia e Tecnologia) [Pest-C/EQB/LA0006/2013]
- ON.2 QREN - Quadro de Referencia Estrategico Nacional - QREN
- FEDER
- FCT [NORTE-07-0124-FEDER-000067]
Inflammation plays a crucial role in rheumatoid arthritis progress. In the present work, a novel stealth polymeric nanospheres platform able to carry anti-inflammatory drugs and an imaging agent was developed. Incorporation of gold nanoparticles will allow photoacoustic imaging and near infra-red photothermal application. Through emulsion-diffusion evaporation technique methotrexate and gold nanoparticles were incorporated in the pegylated-poly(DL-lactic-co-glycolic acid) nanospheres. In vitro drug release assays revealed pH and temperature-dependence on gold nanoparticles. Blank nanospheres exhibited negligible in vitro cytotoxicity, while methotrexate-loaded nanospheres hampered monocytes and macrophages viability at a higher level than free methotrexate. Confocal fluorescent microscopy and flow cytometry revealed effective nanospheres internalization, and that their cellular uptake was energy dependent mediated by caveolae and clathrin-endocytosis mechanism. Finally, MTX-loaded multifunctional nanospheres containing gold lead to a significant reduction of IL-1 beta, IL-6 and TNF-alpha inflammatory cytokines produced by monocytes and macrophages upon in vitro inflammatory stimulation, suggesting a favorable anti-inflammatory activity. These results confirm that the multifunctional nanospheres represent a promising theranostic platform for RA diagnosis and intracellular treatment, by combining methotrexate and gold nanoparticles for a highly effective targeted chemo-photothermal therapy. (C) 2015 Elsevier B.V. All rights reserved.
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