Silicane Derivative Increases Doxorubicin Efficacy in an Ovarian Carcinoma Mouse Model: Fighting Drug Resistance

0544209 - ÚOCHB 2022 RIV US eng J - Journal Article
Fojtů, M. - Balvan, J. - Vičar, T. - Holcová Polanská, H. - Peltanová, B. - Matějková, Stanislava - Raudenská, M. - Šturala, J. - Mayorga-Burrezo, P. - Masařík, M. - Pumera, M.
Silicane Derivative Increases Doxorubicin Efficacy in an Ovarian Carcinoma Mouse Model: Fighting Drug Resistance.
ACS Applied Materials and Interfaces. Roč. 13, č. 27 (2021), s. 31355-31370. ISSN 1944-8244. E-ISSN 1944-8252
Institutional support: RVO:61388963
Keywords : 2D nanomaterials * silicene * polysiloxane * nanosheets * targeted drug delivery * doxorubicin * ovarian cancer * drug resistance
OECD category: Analytical chemistry
Impact factor: 10.383, year: 2021
Method of publishing: Limited access
https://doi.org/10.1021/acsami.0c20458

The development of cancer resistance continues to represent a bottleneck of cancer therapy. It is one of the leading factors preventing drugs to exhibit their full therapeutic potential. Consequently, it reduces the efficacy of anticancer therapy and causes the survival rate of therapy-resistant patients to be far from satisfactory. Here, an emerging strategy for overcoming drug resistance is proposed employing a novel two-dimensional (2D) nanomaterial polysiloxane (PSX). We have reported on the synthesis of PSX nanosheets (PSX NSs) and proved that they have favorable properties for biomedical applications. PSX NSs evinced unprecedented cytocompatibility up to the concentration of 300 μg/mL, while inducing very low level of red blood cell hemolysis and were found to be highly effective for anticancer drug binding. PSX NSs enhanced the efficacy of the anticancer drug doxorubicin (DOX) by around 27.8–43.4% on average and, interestingly, were found to be especially effective in the therapy of drug-resistant tumors, improving the effectiveness of up to 52%. Fluorescence microscopy revealed improved retention of DOX within the drug-resistant cells when bound on PSX NSs. DOX bound on the surface of PSX NSs, i.e., PSX@DOX, improved, in general, the DOX cytotoxicity in vitro. More importantly, PSX@DOX reduced the growth of DOX-resistant tumors in vivo with 3.5 times better average efficiency than the free drug. Altogether, this paper represents an introduction of a new 2D nanomaterial derived from silicane and pioneers its biomedical application. As advances in the field of material synthesis are rapidly progressing, novel 2D nanomaterials with improved properties are being synthesized and await thorough exploration. Our findings further provide a better understanding of the mechanisms involved in the cancer resistance and can promote the development of a precise cancer therapy.
Permanent Link: http://hdl.handle.net/11104/0321255