Synthesis of mesoporous silica nanoparticle–oxaliplatin conjugates for improved anticancer drug delivery

• Conjugating an active anticancer species of oxaliplatin onto mesoporous silica nanoparticles (MSN) for the first time.
• Drug carriers bearing 1,2-bidentate carboxyl groups were synthesized via a convenient protocol.
• MSN-Pt demonstrated an improved cytotoxicity against HepG-2 cells than that of free oxaliplatin.
• MSN-Pt displayed higher level of platinum content both in cells and DNA than that of free oxaliplatin.

Mesoporous silica nanoparticles (MSN) with 1,2-bidentate carboxyl groups on the surface reacted with 1,2-diaminecyclohexano platinum(II) dinitrate (DACH-Pt-(NO3)2) which is an active anticancer species of clinic relevant oxaliplatin to form MSN-Pt. The modification of the parent particles was monitored by 13C, 29Si solid-state NMR, X-ray measurements (XRD) and Fourier transform infrared spectroscopy (FT-IR). After loading with platinum drugs, MSN-Pt exhibited two strong Pt4f signals as indicated by X-ray photoelectron spectroscopy (XPS). The platinum content in the conjugates was calculated to be 9.7% according to ICP-MS measurements. Confocal laser scanning microscopy (CLSM) displayed that MSN-Pt were uptaken fast by HepG-2 cells and concentrated within endosomes and lysosomes. In vitro MTT assay of MSN-Pt demonstrated an improved cytotoxicity against HepG-2 cells than that of free oxaliplatin. This is due to the fact that MSN-Pt expressed higher platinum intracellular uptake and more DNA binding (Pt-DNA adducts) than free oxaliplatin. Hence this work highlighted that the platinum loaded MSN nanoparticles could be a promising future intelligent drug delivery system.

Figure optionsDownload as PowerPoint slide