DNA-Conjugated Amphiphilic Aggregation-Induced Emission Probe for Cancer Tissue Imaging and Prognosis Analysis

Abstract

Detection of an ultralow concentration of mRNA is important in the prognosis of gene-related diseases. In this study, a DNA-conjugated amphiphilic aggregation-induced emission probe (TPE-R-DNA) was synthesized for cancer tissue imaging and prognosis analysis based on an exonuclease III-aided target recycling technique. TPE-R-DNA comprise two components: a hydrophobic component that serves as the "turn-on" long wavelength fluorescence imaging agent (TPE-R-N); and a hydrophilic single DNA strand (Alk-DNA) which acts as specific recognition part for target mRNA. In the absence of target mRNA, TPE-R-DNA had almost no fluorescence because of its high water solubility. Conversely, the TPE-R-DNA was digested by exonuclease III (Exo III) in the presence of MnSOD mRNA to release the hydrophobic fluorogens (TPE-R-AT). Subsequently, TPE-R-AT formed aggregates, and therefore, fluorescence signal was distinctly observed. For the first time, the structure of the hydrolysis product (TPE-R-AT), containing two bases A and T, was proved by the mass spectrum (MS) and high-performance liquid chromatography (HPLC). Moreover, the detection limit toward mRNA could be achieved in as low as 0.6 pM. Furthermore, the fluorescent signal can be used to confirm the MnSOD mRNA expression level in cancer tissue. The MnSOD mRNA expression in renal cancer was lower than in renal cancer adjacent tissue. In particular, the expression level was analyzed to predict prognosis of cancer patients. Our results demonstrate that a shorter survival time was evident among patients in lower MnSOD mRNA expression. Thereby, it indicates great potential for the development of an ultrasensitive biosensing platform for the application in disease prognosis.

Biomacromolecule‐Functionalized AIEgens for Advanced Biomedical Studies

“…Figure B shows that the yellow fluorescence intensity of TPEPy‐LDNA was time‐dependent increase in living MCF‐7 cells, and these results indicated that TPEPy‐LDNA had superior performance such as good photostability and biocompatibility. In 2018, on the basis of previous efforts, TPE‐R‐DNA was designed and synthesized for detecting manganese superoxide dismutase (MnSOD) mRNA by Xia and co‐workers TPE‐R‐DNA was highly selective and sensitive to detect MnSOD mRNA and its detection limit was as low as 0.6 pM in vitro. From the Figure C, the level of MnSOD mRNA in HeLa cells and MCF‐7 cells was showed by red fluorescent intensity of TPE‐R‐DNA.…”

“…C) The chemical conjugate structure of DNA‐functionalized TPE TPE‐R‐DNA and its detection toward MnSOD mRNA in living cells and tissues. Adapted with permission . Copyright 2018, American Chemical Society.…”

A new approach to developing diagnostics and therapeutics: Aggregation‐induced emission‐based fluorescence turn‐on

“…It has been reported that manganese superoxide dismutase (MnSOD), translated from MnSOD messenger RNA (mRNA), can protect the heart against ischemia/reperfusion injury and possesses antitumor activity . Therefore, Wang et al synthesized 6 (Figure ) to detect MnSOD mRNA expression level in cancer tissues. The DNA portion of the probe contained the partial complementary base sequence of the MnSOD mRNA.…”

AIEgens/Nucleic Acid Nanostructures for Bioanalytical Applications

“…Recently,o ur group prepared aD NA-combined amphiphilic AIE probe (TPE-R-DNA) that was capable of imaging cancer tumors and outcome analysisb yu sing an Exo III-aided target recycling strategy (Figure12). [51] TPE-R-DNA wasc omposed of ah ydrophobic element( TPE-R-N 3 )a cting as as ignal reporter and ah ydrophilic single DNA strand as the recognition element. In the absence of MnSOD mRNA, TPE-R-DNA exhibited negligible fluorescence owing to the high water dispersibility.…”