Graphene Quantum Dot-Based Nanocomposites for Diagnosing Cancer Biomarker APE1 in Living Cells

Abstract

As an essential DNA repair enzyme, apurinic/apyrimidinic endonuclease 1 (APE1) is overexpressed in most human cancers and is identified as a cancer diagnostic and predictive biomarker for cancer risk assessment, diagnosis, prognosis, and prediction of treatment efficacy. Despite its importance in cancer, however, it is still a significant challenge nowadays to sense abundance variation and monitor enzymatic activity of this biomarker in living cells. Here, we report our construction of biocompatible functional nanocomposites, which are a combination of meticulously designed unimolecular DNA and fine-sized graphene quantum dots. Upon utilization of these nanocomposites as diagnostic probes, massive accumulation of fluorescence signal in living cells can be triggered by merely a small amount of cellular APE1 through repeated cycles of enzymatic catalysis. Most critically, our delicate structural designs assure that these graphene quantum dot-based nanocomposites are capable of sensing cancer biomarker APE1 in identical type of cells under different cell conditions and can be applied to multiple cancerous cells in a highly sensitive and specific manners. This work not only brings about new methods for cytology-based cancer screening but also lays down a general principle for fabricating diagnostic probes that target other endogenous biomarkers in living cells.

A Multiparametric Evaluation of Quantum Dot Size and Surface-Grafted Peptide Density on Cellular Uptake and Cytotoxicity

“…2 QDs are semiconductor nanocrystals comprised of a core with a diameter ranging typically ranging between 1 and 10 nm and possess high brightness, photostability, 3 broad excitation and narrow and size-tunable emission spectra 4 which render them powerful probes for in vitro and in vivo biomedical imaging applications at the molecular and diagnostic level. [5][6][7] The ability of multiple-sized QDs to be excited by a single wavelength allows efficient multiplexing and the simultaneous detection of various biomarkers in tissue sections, improving the predictability of clinical outcomes. 8,9 Secondly, their high intensity and resistance towards photobleaching permit the longterm tracking of live, single-molecules, which offers detailed information on intracellular trafficking and processing.…”

Intramolecular Orthogonal Reporters for Dissecting Oxidative Stress and Response

“…APE1 speci cally cleaves AP site and therefore plays a signi cant role in BER pathway, particularly in the ROS-regulated BER 23 . Abnormal expression and subcellular distribution of APE1 have been linked to tumor development 24,25 . As our previous study, the simple uorescence dequenching of nucleic acid probes can be used for monitoring and quantifying the enzyme activity 26,27 .…”

Graphene and its derivatives: understanding the main chemical and medicinal chemistry roles for biomedical applications

“…The researchers also carried out tests that emphasized the high carrying capacity of the nanosystem, demonstrating its promising application as a bimodal agent in the diagnosis and therapy of cancer. In another study reported by Zhang et al developed a nanocomposite with diagnostic functionality using the apurinic/apyrimidinic endonuclease 1 ( APE1 ) enzyme as a biomarker, as it is overexpressed in most human cancers [ 259 ]. This nanocomposite originated from the unification through adsorption of GQDs and unimolecular DNA architectures acting as a ligand to APE1.…”