Drug resistance in bacteria and cancer is a growing problem that decreases drug treatment effectiveness and increases the severity of bacterial infections as well as cancer mortality. Due to their high sensitivity, low cost, and rapid analysis time, electrochemical methods have been increasingly employed to tackle this challenge throughout the last decade. This review covers literature on the electrochemical characterization of antibiotics and chemotherapeutic drugs, as well as advances in analyzing interactions between drug compounds and biological cells. Recent developments towards the quantitative detection of drug resistance in bacteria and cancer by electrochemistry are discussed, and the use of specialized electrochemical instrumentation, such as scanning electrochemical microscopy, is highlighted.
Drug resistance in bacteria and cancer is a growing problem that severely increases the number of deaths worldwide.[1,2] According to the World Health Organization, drug resistance is present in every country, and various national and international health organizations have called for the urgent development of new treatment and diagnostic strategies.[3] This presentation outlines innovative and interdisciplinary approaches to recognize and quantify drug resistance in bacteria and cancer cells by electrochemistry. Electroanalytical techniques are cost efficient, sensitive and the transparency of a liquid sample is irrelevant, allowing direct in vitro analysis of blood, urine, and saliva samples. This presentation covers the characterization of some of the most important commercial drugs, and new investigational antibiotic hybrids by electrochemistry.[4] Building on this exploration of drug electrochemistry, the quantification of drug uptake and retention in biological cells is presented. This research forms the basis for the development of a point-of-care biosensors to identify drug resistance in patient samples. This technology will advance clinical treatment from the current trial-and-error approach to the prescription of evidence-based personalized drug regimens. [1] J. Sun, A. R. Warden, J. Huang, W. Wang, and X. Ding, Anal. Chem., 91, 7524–7530 (2019). [2] R. Article, J. Pathol., 205, 275–292 (2005). [3] World Health Organization (WHO). Global action plan on antimicrobial resistance; (2015). [4] R. Islam, H.T. Le Luu, S. Kuss, J. Electrochem. Soc., 167, 045501 (2020).
Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecological cancers and affects patients on all continents. Primary treatments involve surgery and the administration of chemotherapeutics, such as carboplatin, which is listed by the World Health Organization as an essential medication for the treatment of human cancers. Unfortunately, due to high rates of drug resistance of EOC towards carboplatin, cancer relapse rates are devastating, and the mechanisms of chemoresistance to carboplatin have not been adequately identified. Consequently, there is a dire need for innovative strategies that are able to detect carboplatin resistance in cancer and to further our understanding of the fundamental nature of chemoresistance towards carboplatin. The presented work describes the thorough electrochemical characterization of carboplatin. We quantify the uptake of carboplatin by ovarian cancer cells by electrochemistry to better understand mechanisms of carboplatin chemoresistance. Results emerging from this research will be important for future medical research developing novel agents to combat chemoresistance.
The rapid spread of drug resistance in bacteria as well as cancer has developed into a significant threat to the global public health. According to the World Health Organization (WHO), antibiotic resistance is present in every country, and various national and international health organizations, including the United Nations and the Infectious Diseases Society of America have called for the urgent development of new treatment and diagnostic strategies. The Centers for Disease Control and Prevention reports approximately 10 million deaths worldwide each year in connection with antibiotic resistance. Similarly, drug resistance in cancer is believed to be responsible for treatment failure in up to 90% of metastatic cancer patients. Cellular resistance mechanisms in both bacteria and cancer include cell membrane protein modifications, intracellular drug target alterations, and the over expression of efflux pumps. The latter are the result of an over-expression of efflux pump proteins, which enable cells to expel drugs rapidly from the cell interior, before these compounds can take effective action. Drug compounds and efflux pump proteins have recently caught the attention by the electrochemical community to develop new methodologies to understand and detect drug resistance in both bacteria and cancer by electrochemistry. Our research efforts focus specifically on drug compounds expelled from living biological cells by electrochemistry and their detection by standard electrochemical techniques, such as volatmmetry, as well as specialized instrumentation, such as scanning electrochemical microscopy (SECM). This presentation covers the characterization of common drug compounds, but also newly investigational antibiotic hybrids. Recent advances are presented towards the quantification of drug resistance in epithelial ovarian cancer (EOC), which has the highest mortality rate among gynecological cancers.
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