Nanoarchitectured Electrochemical Cytosensors for Selective Detection of Leukemia Cells and Quantitative Evaluation of Death Receptor Expression on Cell Surfaces

Abstract

The variable susceptibility to the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment observed in various types of leukemia cells is related to the difference in the expression levels of death receptors, DR4 and DR5, on the cell surfaces. Quantifying the DR4/DR5 expression status on leukemia cell surfaces is of vital importance to the development of diagnostic tools to guide death receptor-based leukemia treatment. Taking the full advantages of novel nanobiotechnology, we have developed a robust electrochemical cytosensing approach toward ultrasensitive detection of leukemia cells with detection limit as low as ~40 cells and quantitative evaluation of DR4/DR5 expression on leukemia cell surfaces. The optimization of electron transfer and cell capture processes at specifically tailored nanobiointerfaces and the incorporation of multiple functions into rationally designed nanoprobes provide unique opportunities of integrating high specificity and signal amplification on one electrochemical cytosensor. The high sensitivity and selectivity of this electrochemical cytosensing approach also allows us to evaluate the dynamic alteration of DR4/DR5 expression on the surfaces of living cells in response to drug treatments. Using the TRAIL-resistant HL-60 cells and TRAIL-sensitive Jurkat cells as model cells, we have further verified that the TRAIL susceptibility of various types of leukemia cells is directly correlated to the surface expression levels of DR4/DR5. This versatile electrochemical cytosensing platform is believed to be of great clinical value for the early diagnosis of human leukemia and the evaluation of therapeutic effects on leukemia patients after radiation therapy or drug treatment.

Recent advances in nanostructures and nanocrystals as signal-amplification elements in electrochemical cytosensing

“…More recently, Zheng et al [22] prepared HRP-TRAIL-Fe 3 O 4 @Au nanoprobes using a LBLassembly approach as illustrated in Scheme 2. Then, HRP-TRAIL-Fe 3 O 4 @Au modified GCE were used for detection of HL-60 cells.…”

A sensitive electrochemiluminescence cytosensor for quantitative evaluation of epidermal growth factor receptor expressed on cell surfaces

“…It is attracted considerable interest and has been widely used in immunoassay [8,9], DNA analysis [10], clinical diagnosis [9,11], carbohydrate analysis [12] and cytosensing [11,13]. Although Han et al [14] have used ECL technique monitor the cell-surface carbohydrate expression [15].…”

“…In comparison to monoclonal antibodies, aptamers have low molecular weights and can be chemically synthesized and readily modified. Thus, aptamers have been recognized as reliable affinity ligands for recognition and monitoring of proteins in serum and cell media [11]. What's more, aptamers have been used to distinguish different cell lines and identify the native protein targets on the cell surface [16].…”

“…Magnetic beads (MBs) have been widely used for screening cells in biological technology. It has been used as carriers for smaller nanoparticles or biomolecules, attributing to its relatively large surface area [11]. What's more, MBs has been also used for the signal amplification by loading luminescentprobe.…”

“…Zhang et al [19] reported an electrochemical cytosensor by in situ chemical inertness of PANI-NFs with gold nanoparticles for monitoring of T-cell activation. Zheng et al [11] utilized an electrochemical nanoprobe for the quantitative evaluation of DR4/ DR5 expression on leukemia cell surfaces through coimmobilization of both recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) and horseradish peroxidase (HRP) on Au NPs-decorated magnetic Fe 3 O 4 beads which was used for the signal amplification. Here, the positively-charged PANI-NF was choosed to combine with the negatively-charged GO for improving the effective area of three-dimensional structure.…”