ABSTRACT
The nanoscale optical resolution achieved using near-field scanning optical microscopy (NSOM) has the potential to allow new approaches and insight into subcellular function, and intermolecular interaction or intramolecular dynamics at the single-molecule level in cells. In this chapter, we describe the use of NSOM to detect the cellular localization and the effect of multidrug-resistance (MDR) proteins on chemotherapeutic regimens. The MDR phenotype is mainly associated with overexpression of members of the ATP-binding cassette (ABC) protein family. We have investigated the localization of P-glycoprotein (Pgp), and how they confer resistance to chemotherapy drugs in cancer cells. The presence of Pgp proteins in the plasma membrane and in the intracellular membranes decreased the intracellular accumulation of tetramethyl rhodamine ester and increased the efflux of anthracycline doxorubicin from the nucleus. Accurate localization of these proteins in substructures of cells and cellular organelles will enable a better understanding of structure–function relationships and allow new strategies for the development of highly specific MDR modulator and antitumor drugs.
