Dual-drug delivery by porous silicon nanoparticles for improved cellular uptake, sustained release, and combination therapy

作者：Wang Chang Fang^*; Makila Ermei M; Kaasalainen Martti H; Hagstrom Marja V; Salonen Jamb J; Hirvonen Jouni T; Santos Helder A

来源：Acta Biomaterialia, 2015, 16: 206-214.

DOI：10.1016/j.actbio.2015.01.021

• Intracellular uptake
• Sustained drug release
• Combination therapy
• Porous silicon nanoparticles
• Methotrexate/Sorafenib

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.

• 出版日期2015-4-1