Towards multidrug resistance quantification using scanning electrochemical microscopy

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Cancer cells actively defend themselves through multidrug resistance. Its overwhelming presence in many different cancer types, including acute leukemia, colon, kidney, pancreas, and carcinoid cancers, seriously undermines the success of current chemotherapeutical treatments and patient survival rates. Although promising and often irreplaceable, many of these treatments are inefficient because they target a cellular resistance phenotype that is poorly quantified. It has therefore become urgent to develop new bioanalytical methods with improved robustness and sensitivity that can precisely quantify the multidrug resistance associated with different cancer types. As such, our research program is dedicated at demonstrating that biological scanning electrochemical microscopy (SECM) could be the method of choice since it evaluates cell metabolism by measuring the flux of electrochemical probes that are transported in and out of cells, a phenomena that mimics drug resistance. To be convincing, SECM measurements must be validated on different cell lines (resistant and control) that are co-immobilized in defined patterns on nonconductive (e.g., plastic) supports. The objective of the present discovery grant is to perform the SECM measurements on different strains of human cancer cells that specifically overexpress the multidrug resistant protein, MRP1. Within the allowed five-year timetable, this will involve the design of a soft-lithography method capable of co-immobilizing different cell lines (cancerous and control) on a plastic support (e.g., made of Zeonor or polystyrene), the evaluation of the expression levels of MRP1 in the chosen human lung and cervical cancer cell lines, and the validation of a general electrochemical protocol capable of quantifying the resistant signature of the patterned cancer cells.