Evaluation of Multidrug Resistance of Leukemia Using Surface-Enhanced Raman Scattering Method for Clinical Applications.

Abstract

P-glycoprotein (P-gp) is an important multidrug resistance (MDR) regulator for leukemia to mediate its development and thus can be considered as a powerful reference for the diagnosis of MDR. The detection of P-gp is of vital significance and has attracted considerable concerns. In this study, we proposed a surface-enhanced Raman scattering (SERS) method for the evaluation of P-gp expression levels in leukemia cell lines. Basically, we utilized an aqueous phase sandwich-type immunoassay to analyze the expression of P-gp. First, anti-CD45-decorated magnetic beads (MBs) and P-gp antibody-decorated SERS probes were fabricated. CD45 is a common protein expressed in all leukemia cells. As a result, a sandwich immunocomplex can be formed by the MBs, P-gp-overexpressed leukemia cells, and SERS probes. The expression level of P-gp determines the amount of SERS probes that can be captured. Consequently, the SERS intensity of the immunocomplex can be used to evaluate the expression level of P-gp. In a typical procedure, we measured the P-gp expression of an MDR leukemia cell line (K562/ADM) as well as unprocessed whole-blood samples. The SERS intensity of K562/ADM cells was highly correlated with the extent of MDR or the incubation time of adriamycin (which is an MDR inducing drug). In addition, the SERS intensity of the refractory/relapsing group was about sixfolds of that of the control group ( P < 0.01). These results demonstrated that the proposed method holds excellent sensitivity, specificity, reliability, and application potential in assessing both cultured cells and clinical samples. With these outstanding features, we anticipated that such a SERS-based method could be very helpful for the clinical diagnosis of early-stage MDR in leukemia.