Silicane Derivative Increases Doxorubicin Efficacy in an Ovarian Carcinoma Mouse Model: Fighting Drug Resistance
| Autor: | Martina Raudenská, Stanislava Matějková, Hana Polanska, Martin Pumera, Barbora Peltanová, Jiří Šturala, Michaela Fojtů, Tomas Vicar, Michal Masařík, Paula Mayorga-Burrezo, Jan Balvan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Materials science
Siloxanes Drug resistance 010402 general chemistry 01 natural sciences Mice 03 medical and health sciences In vivo Cell Line Tumor Ovarian carcinoma Materials Testing medicine Animals Humans General Materials Science Doxorubicin Free drug Cell Proliferation 030304 developmental biology Ovarian Neoplasms 0303 health sciences medicine.disease Hemolysis Nanostructures 0104 chemical sciences 3. Good health Disease Models Animal Targeted drug delivery Drug Resistance Neoplasm Cancer research Female Ovarian cancer medicine.drug |
| Zdroj: | ACS Applied Materials & Interfaces. 13:31355-31370 |
| ISSN: | 1944-8252 1944-8244 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|