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Article

pH-Responsive Release of Ruthenium Metallotherapeutics from Mesoporous Silica-Based Nanocarriers

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BioSense Institute, University of Novi Sad, Dr Zorana Đinđića 1, 21000 Novi Sad, Serbia
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Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Strasse 2, 06217 Merseburg, Germany
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Department of Bioorganic Chemistry, Leibniz-Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany
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Department of Civil, Geo and Environmental Engineering, Chair of Urban Water Systems Engineering, Technical University of Munich, Am Coulombwall 3, 85748 Garching, Germany
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Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia
*
Authors to whom correspondence should be addressed.
Academic Editors: Montserrat Colilla and Isabel Izquierdo-Barba
Pharmaceutics 2021, 13(4), 460; https://doi.org/10.3390/pharmaceutics13040460
Received: 27 February 2021 / Revised: 19 March 2021 / Accepted: 23 March 2021 / Published: 28 March 2021
Ruthenium complexes are attracting interest in cancer treatment due to their potent cytotoxic activity. However, as their high toxicity may also affect healthy tissues, efficient and selective drug delivery systems to tumour tissues are needed. Our study focuses on the construction of such drug delivery systems for the delivery of cytotoxic Ru(II) complexes upon exposure to a weakly acidic environment of tumours. As nanocarriers, mesoporous silica nanoparticles (MSN) are utilized, whose surface is functionalized with two types of ligands, (2-thienylmethyl)hydrazine hydrochloride (H1) and (5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)hydrazine (H2), which were attached to MSN through a pH-responsive hydrazone linkage. Further coordination to ruthenium(II) center yielded two types of nanomaterials MSN-H1[Ru] and MSN-H2[Ru]. Spectrophotometric measurements of the drug release kinetics at different pH (5.0, 6.0 and 7.4) confirm the enhanced release of Ru(II) complexes at lower pH values, which is further supported by inductively coupled plasma optical emission spectrometry (ICP-OES) measurements. Furthermore, the cytotoxicity effect of the released metallotherapeutics is evaluated in vitro on metastatic B16F1 melanoma cells and enhanced cancer cell-killing efficacy is demonstrated upon exposure of the nanomaterials to weakly acidic conditions. The obtained results showcase the promising capabilities of the designed MSN nanocarriers for the pH-responsive delivery of metallotherapeutics and targeted treatment of cancer. View Full-Text
Keywords: pH-responsive drug delivery; mesoporous silica nanoparticles; ruthenium-based anticancer drugs; controlled drug delivery; cancer treatment pH-responsive drug delivery; mesoporous silica nanoparticles; ruthenium-based anticancer drugs; controlled drug delivery; cancer treatment
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MDPI and ACS Style

Mladenović, M.; Morgan, I.; Ilić, N.; Saoud, M.; Pergal, M.V.; Kaluđerović, G.N.; Knežević, N.Ž. pH-Responsive Release of Ruthenium Metallotherapeutics from Mesoporous Silica-Based Nanocarriers. Pharmaceutics 2021, 13, 460. https://doi.org/10.3390/pharmaceutics13040460

AMA Style

Mladenović M, Morgan I, Ilić N, Saoud M, Pergal MV, Kaluđerović GN, Knežević NŽ. pH-Responsive Release of Ruthenium Metallotherapeutics from Mesoporous Silica-Based Nanocarriers. Pharmaceutics. 2021; 13(4):460. https://doi.org/10.3390/pharmaceutics13040460

Chicago/Turabian Style

Mladenović, Minja, Ibrahim Morgan, Nebojša Ilić, Mohamad Saoud, Marija V. Pergal, Goran N. Kaluđerović, and Nikola Ž. Knežević 2021. "pH-Responsive Release of Ruthenium Metallotherapeutics from Mesoporous Silica-Based Nanocarriers" Pharmaceutics 13, no. 4: 460. https://doi.org/10.3390/pharmaceutics13040460

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