2D Germanane Derivative as a Vector for Overcoming Doxorubicin Resistance in Cancer Cells

Michaela Fojtů, Jan Balvan, Martina Raudenská, Tomáš Vičar, Jiří Šturala, Zdeněk Sofer, Jan Luxa, Jan Plutnar, Michal Masařík, Martin Pumera

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9 Citations (Scopus)

Abstract

Cancer resistance to chemotherapeutics is a common problem often encountered in the clinical setting, hampering greatly the conventional therapy of malignant diseases for several decades. No generally efficient mechanism solving this phenomenon was found so far. Cancer cells can adapt to a stress applied in the form of chemotherapeutics and become insensitive to their effects. Under such a selection pressure, the cancer cells acquire features helping them not only to survive the changes in the environment but also to further divide and to form secondary lesions. Therefore, besides developing novel chemotherapeutics, refining the drug delivery mechanisms of the conventional ones is absolutely crucial to defeat the cancer, so we can fully benefit from the effects these therapeutics offer. Here, we demonstrated enhanced delivery of doxorubicin (DOX) to a DOX-resistant ovarian cancer cell line using completely novel 2D material 4-carboxybutylgermanane (Ge-Bu-COOH). In our study, we present Ge-Bu-COOH as a drug carrier evincing high drug-loading efficiency, low cytotoxicity up to the concentration of 2.5 μg/mL and no hemolysis. Simultaneously, binding DOX to Ge-Bu-COOH increases DOX accumulation in the DOX-resistant cell lines. It leads to a significant anticancer efficiency enhancement in A2780/ADR DOX-resistant cell line; with the maximal effect reaching up to 62.8% compared to free DOX. These findings have profound influence on understanding the behaviour of doxorubicin-resistant tumours and open new horizon to manage their treatment.

Original languageEnglish
Article number100697
JournalApplied Materials Today
Volume20
DOIs
Publication statusPublished - 2020 Sept

Bibliographical note

Funding Information:
M.P. acknowledges the financial support of Grant Agency of the Czech Republic (EXPRO: 19-26896X). M.M. was supported by the project “Center for Tumor Ecology – Research of the Cancer Microenvironment Supporting Cancer Growth and Spread” (reg. no. CZ.02.1.01/0.0/0.0/16_019/0000785) supported by the Operational Program Research, Development and Education. Z. S. was further supported by the Neuron Foundation. M.F. was further supported by funds from the Faculty of Medicine MU to junior researcher.

Funding Information:
M.P. acknowledges the financial support of Grant Agency of the Czech Republic (EXPRO: 19-26896X). M.M. was supported by the project ?Center for Tumor Ecology ? Research of the Cancer Microenvironment Supporting Cancer Growth and Spread? (reg. no. CZ.02.1.01/0.0/0.0/16_019/0000785) supported by the Operational Program Research, Development and Education. Z. S. was further supported by the Neuron Foundation. M.F. was further supported by funds from the Faculty of Medicine MU to junior researcher.

Publisher Copyright:
© 2020

All Science Journal Classification (ASJC) codes

  • Materials Science(all)

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