Multifunctional nanospheres for co-delivery of methotrexate and mild hyperthermia to colon cancer cells

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Costa Lima, SAC (Author) Other; Gaspar, A (Author) Other; Salette Reis (Author) FFUP; Duraes, L (Author) Other

Journal

Title: MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS

Vol. 75

Pages: 1420-1426

ISSN: 0928-4931

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 6 Citations

Scopus - 16 Citations

Other information

Authenticus ID: P-00M-HM0

DOI: 10.1016/j.msec.2017.03.049

Abstract (EN): A multifunctional nanomedicine platform was designed and evaluated for efficient colon cancer therapy by a combinatorial therapeutic approach based on a chemotherapeutic drug and mild hyperthermia. Advantage was taken from the dual role of methotrexate (MTX), as folate receptor-targeting, overexpressed in tumor cells, and as anticancer drug. Incorporation of superparamagnetic iron oxide nanoparticles (SPIONs) allows to heat cancer cells externally through an alternating magnetic field. The developed nanocarrier was based on polyethylene glycol-polylactic acid (PEG-PLA) nanospheres to improve biocompatibility, enhancing their targeting by prolonging blood circulation time. By an emulsion-evaporation method the nanospheres were produced and then characterized for size distribution, zeta-potential, in vitro drug release profile and cellular studies. The co-delivery of MTX and SPIONs on PEG-PLA nanospheres resulted in nanocarriers with a size of 160 nm in diameter, a polydispersity index below 0.2 and a zeta potential of ca. -18 mV. Multifunctional nanospheres were monodisperse and stable up to 3 months. MTX was released preferentially under mild hyperthermia conditions. The multifunctional nanospheres were able to increase the cytotoxicity of MTX towards Caco-2 and SW-480 colon cancer cells, in comparison to free drug. Also, the nanospheres allowed the incorporated MTX to induce greater cell cycle arrest and apoptotic effects than the free MTX. This study provides evidences that MTX-SPIONs-PEG-PLA nanospheres are a promising solution to address colorectal cancer over-expressing folate receptors, by a combinatory approach.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7