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

Michaela Fojtů, Jan Balvan, Tomáš Vičar, Hana Holcová Polanská, Barbora Peltanová, Stanislava Matějková, Martina Raudenská, Jiří Šturala, Paula Mayorga-Burrezo, Michal Masařík, Martin Pumera

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)31355-31370
Number of pages16
JournalACS Applied Materials and Interfaces
Issue number27
Publication statusPublished - 2021 Jul 14

Bibliographical note

Funding Information:
This work was supported by the funds from the Ministry of Health of the Czech Republic (NU21-08-00407). M.P. acknowledges the financial support from the Grant Agency of the Czech Republic (EXPRO: 19-26896X). M.F. and M.M. were supported by funds from the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic in the year 2021 (MUNI/A/1698/2020 and MUNI/A/1246/2020). M.F. was further supported by the start-up grant from the Faculty of Medicine MU to junior researchers. J.S. acknowledges the financial support from the Grant Agency of the Czech Republic (GACR: 19-17593Y). The authors acknowledge Dr. M. Ešner and the core facility CELLIM team of CEITEC supported by the Czech-BioImaging large RI project (no. LM2018129 funded by MEYS CR) for their support for obtaining the scientific data presented in this paper. Furthermore, they would like to thank Dr. Z. Sofer and Dr. J. Plutnar, for their help with the preparation of the material.

Publisher Copyright:
© 2021 American Chemical Society.

All Science Journal Classification (ASJC) codes

  • Materials Science(all)


Dive into the research topics of 'Silicane Derivative Increases Doxorubicin Efficacy in an Ovarian Carcinoma Mouse Model: Fighting Drug Resistance'. Together they form a unique fingerprint.

Cite this