Journal
ACTA BIOMATERIALIA
Volume 16, Issue -, Pages 206-214Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2015.01.021
Keywords
Intracellular uptake; Sustained drug release; Combination therapy; Porous silicon nanoparticles; Methotrexate/Sorafenib
Funding
- Chinese Scholarship Council [2009627022]
- Academy of Finland [252215, 256394]
- University of Helsinki Research Funds, Biocentrum Helsinki
- European Research Council under the European Union [310892]
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Dual-drug delivery of antiangiogenic and chemotherapeutic drugs can enhance the therapeutic effect for cancer therapy. Conjugation of methotrexate (MTX) to porous silicon (PSi) nanoparticles (MTX-PSi) with positively charged surface can improve the cellular uptake of MTX and inhibit the proliferation of cancer cells. Herein, MTX-PSi conjugates sustained the release of MTX up to 96 h, and the released fragments including MTX were confirmed by mass spectrometry. The intracellular distribution of the MTX-PSi nanoparticles was confirmed by transmission electron microscopy. Compared to pure MTX, the MTX-PSi achieved similar inhibition of cell proliferation in folate receptor (FR) over-expressing U87 MG cancer cells, and a higher effect in low FR-expressing EA.hy926 cells. Nuclear fragmentation analysis demonstrated programmed cell apoptosis of MTX-PSi in the high/low FR-expressing cancer cells, whereas PSi alone at the same dose had a minor effect on cell apoptosis. Finally, the porous structure of MTX-PSi enabled a successful concomitant loading of another anti-angiogenic hydrophobic drug, sorafenib, and considerably enhanced the dissolution rate of sorafenib. Overall, the MTX-PSi nanoparticles can be used as a platform for combination chemotherapy by simultaneously enhancing the dissolution rate of a hydrophobic drug and sustaining the release of a conjugated chemotherapeutic drug. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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