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Preparation, Characterisation, and Measurement of the in vitro Cytotoxicity of Mesoporous Silica Nanoparticles Loaded with Cytotoxic Pt(II) Oxadiazoline Complexes

Authors: G. Wagner, R. Herrmann

Abstract:

Cytotoxic platinum compounds play a major role in the chemotherapy of a large number of human cancers. However, due to the severe side effects for the patient and other problems associated with their use, there is a need for the development of more efficient drugs and new methods for their selective delivery to the tumours. One way to achieve the latter could be in the use of nanoparticular substrates that can adsorb or chemically bind the drug. In the cell, the drug is supposed to be slowly released, either by physical desorption or by dissolution of the particle framework. Ideally, the cytotoxic properties of the platinum drug unfold only then, in the cancer cell and over a longer period of time due to the gradual release. In this paper, we report on our first steps in this direction. The binding properties of a series of cytotoxic Pt(II) oxadiazoline compounds to mesoporous silica particles has been studied by NMR and UV/vis spectroscopy. High loadings were achieved when the Pt(II) compound was relatively polar, and has been dissolved in a relatively nonpolar solvent before the silica was added. Typically, 6-10 hours were required for complete equilibration, suggesting the adsorption did not only occur to the outer surface but also to the interior of the pores. The untreated and Pt(II) loaded particles were characterised by C, H, N combustion analysis, BET/BJH nitrogen sorption, electron microscopy (REM and TEM) and EDX. With the latter methods we were able to demonstrate the homogenous distribution of the Pt(II) compound on and in the silica particles, and no Pt(II) bulk precipitate had formed. The in vitro cytotoxicity in a human cancer cell line (HeLa) has been determined for one of the new platinum compounds adsorbed to mesoporous silica particles of different size, and compared with the corresponding compound in solution. The IC50 data are similar in all cases, suggesting that the release of the Pt(II) compound was relatively fast and possibly occurred before the particles reached the cells. Overall, the platinum drug is chemically stable on silica and retained its activity upon prolonged storage.

Keywords: Cytotoxicity, mesoporous silica, nanoparticles platinum compounds.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1112179

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References:


[1] P. Yang S. Gai and J. Lin, „Functionalized mesoporous silica materials for controlled drug delivery“, Chem. Soc. Rev., 41, 2012, pp. 3679-3698. See also references cited therein.
[2] F. Balas, M. Manzano, P. Horcajada and M. Vallet-Regí, „Confinement and controlled release of bisphosphonates on ordered mesoporous silica-based materials“ J. Am. Chem. Soc., 128, 2006, pp. 8116–8117.
[3] C.-Y. Lai, B. G. Trewyn, D. M. Jeftinija, K. Jeftinija, S. Xu, S. Jeftinija and V. S.-Y. Lin, „A mesoporous silica nanosphere-based carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules“, J. Am. Chem. Soc., 125, 2003, pp. 4451–4459.
[4] J. L. Vivero-Escoto, I. I. Slowing, C.-W. Wu and V. S. Y. Lin, „Photo-induced Intracellular Controlled Release Drug Delivery in Human Cells by Gold-Capped Mesoporous Silica Nanosphere“, J. Am. Chem. Soc., 131, 2009, pp. 3462–3463.
[5] Z. M. Tao, B. Toms, J. Goodisman and T. Asefa, „Mesoporous silica micro-particles enhance the cytotoxicity of anticancer platinum drugs“ ACS Nano, 4, 2010, pp. 789-794.
[6] L. Pasqua, F. Testa, R. Aiello, S. Cundari and J. B. Nagy, „Preparation of bifunctional hybrid mesoporous silica potentially useful for drug targeting“ Micropor. Mesopor. Mater. 103, 2007, pp. 166–173.
[7] B. Ahn, J. Park, K. Singha, H. Park and W. J. Kim, „Mesoporous silica nanoparticle-based cisplatin prodrug delivery and anticancer effect under reductive cellular environment“ J. Mater. Chem. B, 1, 2013, 2829-2836.
[8] J. L. Gu, S. S. Su, Y. S. Li, Q. J. He, F. Y. Zhong, J. L. Shi, „Surface Modification-Complexation Strategy for Cisplatin Loading in Mesoporous Nanoparticles“ J. Phys. Chem. Lett. 1, 2010, pp. 3446-3450.
[9] H. He, H. Xiao, H. Kuanga, Z. Xie, X. Chen, X.Jing, Y. Huang, “Synthesis of mesoporous silica nanoparticle–oxaliplatin conjugates for improved anticancer drug delivery“ Colloids and Surfaces B: Biointerfaces, 117, 2014, pp. 75–81.
[10] A. J. Di Pasqua, S. Wallner, D. J. Kerwood, and J. C. Dabrowiak, „Adsorption of the PtII Anticancer Drug Carboplatin by Mesoporous Silica“ Chemistry & Biodiversity, 6, 2009, pp. 1343-1349.
[11] H. M. Coley, J. Sarju and G. Wagner, “Synthesis and Characterization of Platinum(II) Oxadiazoline Complexes and their In Vitro Antitumor Activity in Platinum Sensitive and Resistant Cancer Cell Lines” J. Med. Chem., 51, 2008, pp. 135-141.
[12] B. Desai, T. N. Danks and G. Wagner, “Ligand Discrimination in the Reaction of Nitrones with (PtCl2(PhCN)2). Selective Formation of Mono-oxadiazoline and Mixed Bis-oxadiazoline Complexes under Thermal and Microwave Conditions.” Dalton Trans., 2004, pp. 166-171.
[13] J. Sarju, J. Arbour, J. Sayer, B. Rohrmoser, W. Scherer and G. Wagner, “Synthesis and Characterisation of Mixed Ligand Pt(II) and Pt(IV) Oxadiazoline Complexes.” Dalton Trans., 2008, pp. 5302-5312.
[14] G. Wagner, A. Marchant and J. Sayer, “Design, Synthesis, Characterisation and Chemical Reactivity of Mixed-ligand Platinum(II) Oxadiazoline Complexes with Potential Cytotoxic Properties.” Dalton Trans., 39, 2010, pp. 7747-7759.
[15] J. M. Rosenholm, A. Meinander, E. Peuhu, R. Neimi, J. E. Ericsson, C. Sahlgren and M. Lindén, „Targeting of porous hybride silica nanoparticles to cancer cells“ ACS Nano, Nanoscale, 3, 2009, pp. 197-208.
[16] ImageJ program, see: http://rsb.info.nih.gov/ij/download.html
[17] J. R. Masters, „HeLa cells 50 years on: the good, the bad and the ugly.“ Nat. Rev. Cancer, 2, 2002, pp. 315-19.
[18] Promega Technical Bulletin TB288, Revised 12/2012, Promega Corporation, 2800 Woods Hollow Road, Madison, WI 53711-5399 USA.
[19] Y. Minagawa, J. Kigawa, H. Ishihara, H. Itamachi and N. Terakawa, “Synergistic enhancement of cisplatin cytotoxicity by SN-38, an active metabolite of CPT-11, for cisplatin resistant HeLa cells.” Jpn. J. Cancer. Res. 85, 1994, pp. 966-971.
[20] K. Takamura, T. Sakaeda, T. Yagami, H Kobayashi, N. Ohmoto, M. Horinouchi, K. Nishiguchi and K. Okumura, “Cytotoxic effect of 27 anticancer drugs in HeLa and MDR-1 overexpressing derivative cell lines.” Biol. Pharm. Bull. 25, 2002, pp 771-778.