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Published on: August 30, 2017
Nanomediator-Effector Cascade Systems for Amplified Protein Kinase Activity Imaging and Phosphorylation-Induced Drug
Fenfen Zheng1,2, Tiantian Meng1, Difei Jiang2
1State Key Laboratory of Analytical Chemistry for life Science, Chemistry and Biomedicine Innovation Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
Abstract:
Protein kinases constitute a rich pool of biomarkers and therapeutic targets of tremendous diseases including cancer. However, sensing kinase activity in vivo while implementing treatments according to kinase hyperactivation remains challenging. Herein, we present a nanomediator-effector cascade system that can in situ magnify the subtle events of kinase-catalyzed phosphorylation via DNA amplification machinery to achieve kinase activity imaging and kinase-responsive drug release in vivo. In this cascade, the phosphorylation-mediated disassembly of DNA/peptide complex on the nanomediators initiated the detachment of fluorescent hairpin DNAs from the nanoeffectors via hybridization chain reaction (HCR), leading to fluorescence recovery and therapeutic cargo release. We demonstrated that this nanosystem simultaneously enabled trace protein kinase A (PKA) activity imaging and on-demand drug delivery for inhibition of tumor cell growth both in vitro and in vivo, affording a kinase-specific sense-and-treat paradigm for cancer theranostics.
Insights
This study introduces a novel nanosystem for in vivo cancer theranostics. It enables sensitive imaging of protein kinase A (PKA) activity and targeted drug delivery to inhibit tumor growth.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Molecular Biology
Background:
- Protein kinases are crucial biomarkers and therapeutic targets for diseases like cancer.
- Sensing kinase activity in vivo and tailoring treatments remains a significant challenge.
Purpose of the Study:
- To develop a nanomediator-effector cascade system for in situ amplification of kinase activity.
- To achieve simultaneous in vivo kinase activity imaging and kinase-responsive drug release for cancer theranostics.
Main Methods:
- Utilized a DNA amplification machinery for signal magnification of kinase-catalyzed phosphorylation.
- Employed a hybridization chain reaction (HCR) for fluorescence recovery and drug release.
- Demonstrated the system's efficacy in trace protein kinase A (PKA) activity imaging and drug delivery.
Main Results:
- The nanosystem successfully magnified subtle phosphorylation events in situ.
- Achieved simultaneous fluorescence recovery for imaging and therapeutic cargo release.
- Demonstrated inhibition of tumor cell growth both in vitro and in vivo.
Conclusions:
- The developed nanosystem offers a kinase-specific sense-and-treat paradigm.
- This approach holds promise for advancing cancer theranostics through precise molecular targeting.
- Enabled sensitive detection of protein kinase A (PKA) activity and targeted cancer therapy.
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