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A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
Published on: July 3, 2013
Quantitative oncogene-mapping within malignant tumors through Multi-parameter MRI based on RNA-triggered nanoprobes
Wenyue Li1,2,3,4, Runjie Wang2, Xinyi Zhang2
1Department of Rehabilitation Medicine, School of Medicine, the Second Affiliated Hospital of South China University of Technology (Guangzhou First People's Hospital), Guangzhou, 510180, China.
Abstract:
Genomic instability is the important foundation and feature of cancer; hence, the precise oncogene detection is crucial for early diagnosis and pathological analysis of tumors. However, the in vivo oncogene-imaging is confronted with great challenge, due to the extremely low copies of oncogene in cancer cells. Herein, we proposed a strategy of T 1/T 2 magnetic resonance imaging (MRI) based on magnetic resonance tuning (MRET) to analyze tumor-associated miRNA quantitatively. The superparamagnetic quencher Fe3O4 nanoparticles and the paramagnetic enhancer Gd-DTPA were integrated by the DNA linker. The AS1411 aptamer was embedded at the end of the DNA linker to effectively target nucleolins that are overexpressed in tumor cells. As hybridization with targeted miRNA, the Gd3+ labeled tumor-associated nucleotide sequence is released, enhancing T 1 signals and enabling specific localization and quantification of the targeted miRNA. The MRET effect was verified in vitro through mixing with varying concentrations of miR-21. Enhanced T 2 signals and activated T 1 signals were visualized in 4T1 or CT26 subcutaneous tumor models in vivo. Ultimately, the quantitative relation between MRI signals and local miR-21 concentration was established in vivo. These results indicated the potential of nanoprobes for tumor-related genes diagnosis and quantification, further affirming the possibility of prompt and precise tumor diagnosis.
Insights
This study introduces a novel magnetic resonance tuning (MRET) imaging method for precise cancer diagnosis. The technique uses targeted nanoprobes to quantify microRNA (miRNA) levels in tumors, enabling early detection.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Nanotechnology
Background:
- Genomic instability is a hallmark of cancer, necessitating precise oncogene detection for early diagnosis.
- Detecting low-abundance oncogenes in vivo remains a significant challenge for current imaging techniques.
Purpose of the Study:
- To develop a quantitative magnetic resonance imaging (MRI) strategy for analyzing tumor-associated microRNA (miRNA) using magnetic resonance tuning (MRET).
- To establish a method for early tumor diagnosis and pathological analysis through precise oncogene quantification.
Main Methods:
- Integrated superparamagnetic iron oxide (Fe3O4) nanoparticles and paramagnetic gadolinium (Gd-DTPA) enhancers via a DNA linker.
- Embedded AS1411 aptamers for targeting overexpressed nucleolins in tumor cells.
- Utilized hybridization with target miRNA to release Gd3+-labeled sequences, enhancing T1 signals for miRNA quantification.
Main Results:
- Verified the MRET effect in vitro with varying concentrations of miR-21.
- Visualized enhanced T2 and activated T1 signals in vivo in 4T1 and CT26 subcutaneous tumor models.
- Established a quantitative correlation between MRI signals and local miR-21 concentration in vivo.
Conclusions:
- The developed nanoprobes show potential for precise tumor-related gene diagnosis and quantification.
- This approach offers a promising avenue for prompt and accurate tumor diagnosis through miRNA analysis.
