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Real-time visualizing and tracing of HSV-TK/GCV suicide gene therapy by near-infrared fluorescent quantum dots
Dan Shao1, Jing Li, Xuanang Xiao
1Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University , Changchun 130021, China.
Abstract:
Exploring intracellular behavior of suicide gene is significant for improving the efficacy and safety of herpes simplex virus thymidine kinase gene/ganciclovir (HSV-TK/GCV) system in cancer therapy. Molecular imaging represents a powerful tool to understand gene transportation and function dynamics. In this work, we reported a quantum-dot-based technique for revealing the procedure of HSV-TK/GCV suicide gene therapy by constructing covalent linkage between near-infrared fluorescent quantum dots (QDs) and TK gene. This stable QD labeling did not influence either the QDs fluorescence or the biological activity of TK gene. Furthermore, we visualized and dynamically traced the intracellular behavior antitumor effect of TK gene in vitro and in vivo. It is demonstrated that TK gene was shuttled to the nucleus after a-24 h treatment; at that time the single dose of GCV administration exerts the gradually increasing lethal effect until to 72 h. Real-time tracing the formation of hepatocellular carcinoma treated with HSV-TK/GCV suicide gene system in vivo by QD-based NIR fluorescence imaging provides useful insight toward QD-based theranostics in future cancer therapy.
Insights
Quantum dots visualize herpes simplex virus thymidine kinase gene/ganciclovir (HSV-TK/GCV) therapy. This allows real-time tracking of gene behavior and therapeutic effects in cancer treatment.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Cancer Therapy
Background:
- The herpes simplex virus thymidine kinase gene/ganciclovir (HSV-TK/GCV) system is crucial for cancer therapy.
- Understanding intracellular gene behavior is key to enhancing HSV-TK/GCV efficacy and safety.
- Molecular imaging offers powerful tools for dynamic gene transportation and function analysis.
Purpose of the Study:
- To develop a quantum dot (QD)-based technique for visualizing the intracellular dynamics of the HSV-TK/GCV suicide gene therapy.
- To investigate the intracellular transport and antitumor effects of the TK gene in vitro and in vivo.
- To demonstrate the utility of QD-based near-infrared (NIR) fluorescence imaging for theranostics in cancer therapy.
Main Methods:
- Constructed a covalent linkage between near-infrared fluorescent quantum dots (QDs) and the TK gene.
- Ensured QD labeling did not affect QD fluorescence or TK gene biological activity.
- Utilized QD-based NIR fluorescence imaging to visualize and dynamically trace intracellular gene behavior and therapeutic effects in vitro and in vivo.
Main Results:
- Demonstrated that the TK gene was shuttled to the nucleus within 24 hours post-treatment.
- Observed a gradually increasing lethal effect of ganciclovir (GCV) administration peaking at 72 hours.
- Successfully performed real-time tracing of hepatocellular carcinoma formation treated with the HSV-TK/GCV system in vivo.
Conclusions:
- QD-based labeling provides a stable and effective method for tracking gene therapy components.
- The study elucidates the spatiotemporal dynamics of HSV-TK/GCV gene therapy, crucial for optimizing treatment protocols.
- QD-based NIR fluorescence imaging shows significant potential for theranostic applications in future cancer therapies.
