Temperature-responsive polymeric nanospheres containing methotrexate and gold nanoparticles: A multi-drug system for theranostic in rheumatoid arthritis

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Lima Costa (Author) Other; S.A., (Author) Other; Reis, (Author) FFUP; S., (Author) Other

Journal

Title: Colloids and Surfaces B: Biointerfaces

Vol. 133

Pages: 378-387

ISSN: 0927-7765

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 24 Citations

Scopus - 42 Citations

Scientific classification

FOS: Engineering and technology > Materials engineering

Other information

Authenticus ID: P-00G-J84

DOI: 10.1016/j.colsurfb.2015.04.048

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10