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Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
A multi-channel responsive AuNP@COF core-shell nanoprobe for simultaneous subcellular profiling of multiple cancer
Jian Lv1, Shuai Chang1, Hua-Ying Chen1
1Key Laboratory for Advanced Materials, Feringa Nobel Prize Scientist Joint Research Center Frontiers Science Center for Materiobiology, Dynamic Chemistry School of Chemistry, Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
Abstract:
The abnormal change in the expression profile of multiple cancer biomarkers is closely related to tumor progression and therapeutic effect. Due to their low abundance in living cells and the limitations of existing imaging techniques, simultaneous imaging of multiple cancer biomarkers has remained a significant challenge. Here, we proposed a multi-modal imaging strategy to detect the correlated expression of multiple cancer biomarkers, MUC1, microRNA-21 (miRNA-21) and reactive oxygen (ROS) in living cells, based on a porous covalent organic framework (COF) wrapped gold nanoparticles (AuNPs) core-shell nanoprobe. The nanoprobe is functionalized with Cy5-labeled MUC1 aptamer, a ROS-responsive molecule (2-MHQ), and a miRNA-21-response hairpin DNA tagged by FITC as the reporters for different biomarkers. The target-specific recognition can induce the orthogonal molecular change of these reporters, producing fluorescence and Raman signals for imaging the expression profiles of membrane MUC1 (red fluorescence channel), intracellular miRNA-21 (green fluorescence channel), and intracellular ROS (SERS channel). We further demonstrate the capability of the cooperative expression of these biomarkers, along with the activation of NF-κB pathway. Our research provides a robust platform for imaging multiple cancer biomarkers, with broad potential applications in cancer clinical diagnosis and drug discovery.
Insights
This study introduces a novel nanoprobe for simultaneously imaging multiple cancer biomarkers, including MUC1, microRNA-21, and reactive oxygen species (ROS), in living cells. This advancement offers a powerful tool for cancer diagnosis and drug discovery.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Simultaneous imaging of multiple cancer biomarkers is crucial for understanding tumor progression and therapeutic responses but remains challenging due to low biomarker abundance and imaging limitations.
- Abnormal expression profiles of cancer biomarkers like MUC1, microRNA-21 (miRNA-21), and reactive oxygen species (ROS) are linked to tumor development and treatment efficacy.
- Existing imaging techniques struggle with the simultaneous detection of multiple low-abundance biomarkers in living cells.
Purpose of the Study:
- To develop a multi-modal imaging strategy for the correlated detection of MUC1, miRNA-21, and ROS in living cells.
- To create a novel nanoprobe based on a porous covalent organic framework (COF) wrapped gold nanoparticles (AuNPs) core-shell structure.
- To establish a robust platform for imaging multiple cancer biomarkers with potential applications in clinical diagnosis and drug discovery.
Main Methods:
- A core-shell nanoprobe was designed using porous COF-wrapped AuNPs.
- The nanoprobe was functionalized with a Cy5-labeled MUC1 aptamer, a ROS-responsive molecule (2-MHQ), and an FITC-tagged miRNA-21-responsive hairpin DNA.
- Multi-modal imaging was achieved through fluorescence and Surface-Enhanced Raman Spectroscopy (SERS) detection of orthogonal molecular changes induced by target-specific recognition.
Main Results:
- The nanoprobe successfully enabled simultaneous imaging of membrane MUC1 (red fluorescence), intracellular miRNA-21 (green fluorescence), and intracellular ROS (SERS signal).
- Demonstrated the capability to image the cooperative expression of these biomarkers and the activation of the NF-κB pathway.
- Validated the nanoprobe's effectiveness in detecting correlated expression patterns of multiple cancer biomarkers in living cells.
Conclusions:
- The developed nanoprobe provides a robust platform for multi-modal imaging of multiple cancer biomarkers.
- This strategy overcomes limitations of existing techniques for simultaneous detection of low-abundance biomarkers.
- The research holds significant potential for advancing cancer clinical diagnosis and facilitating drug discovery efforts.
