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Published on: April 25, 2025
Nucleic Acid-Gated Covalent Organic Frameworks for Cancer-Specific Imaging and Drug Release
Peng Gao1, Xiaoying Shen1, Xiaohan Liu1
1College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.
Abstract:
Developing nanoplatforms that simultaneously integrate diagnostic imaging and therapy functions has been a promising but challenging task for cancer theranostics. Herein, we report the rational design of a smart nucleic acid-gated covalent organic framework (COF) nanosystem for cancer-specific imaging and microenvironment-responsive drug release. Cy5 dye-labeled single-stranded DNA (ssDNA) for mRNA recognition was adsorbed on the surface of doxorubicin (Dox)-loaded COF nanoparticles (NPs). Dox loaded in the pores of COF NPs could strengthen the interactions between ssDNA and COF and enhance the fluorescence quenching effect toward Cy5, while the densely coated ssDNA could prevent the leakage of Dox from COF NPs. The obtained nanosystem exhibited low fluorescence signal and Dox release in normal cells; however, the ssDNA could be released by the overexpressed TK1 mRNA in cancer cells to recover the intense fluorescence signal of Cy5, and the loaded Dox could be further released for chemotherapy. Therefore, cancer cell-specific diagnostic imaging and drug release were realized with the rationally developed nanosystem. This work offers a universal nanoplatform for cancer theranostics and a promising strategy for regulating the interaction between COFs and biomolecules.
Insights
This study introduces a smart nucleic acid-gated covalent organic framework (COF) nanosystem for targeted cancer theranostics. The system enables cancer-specific imaging and drug delivery by responding to tumor microenvironment triggers.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Materials Science
- Oncology
Background:
- Developing integrated diagnostic imaging and therapy nanoplatforms for cancer theranostics remains a significant challenge.
- Covalent organic frameworks (COFs) offer potential as drug delivery vehicles due to their tunable structures and high loading capacity.
- Precise control over drug release and imaging signal activation in response to the tumor microenvironment is crucial for effective theranostics.
Purpose of the Study:
- To design and develop a smart nucleic acid-gated COF nanosystem for cancer-specific imaging and microenvironment-responsive drug release.
- To investigate the potential of this nanosystem as a universal platform for cancer theranostics.
- To explore strategies for regulating the interaction between COFs and biomolecules for enhanced therapeutic outcomes.
Main Methods:
- Fabrication of doxorubicin (Dox)-loaded COF nanoparticles (NPs) functionalized with Cy5 dye-labeled single-stranded DNA (ssDNA) for mRNA recognition.
- Evaluation of the nanosystem's drug loading, release kinetics, and fluorescence properties in vitro.
- Assessment of cancer cell-specific imaging and drug release triggered by overexpressed TK1 mRNA in cancer cells.
Main Results:
- The ssDNA coating on Dox-loaded COF NPs effectively prevented premature drug leakage and quenched Cy5 fluorescence.
- In cancer cells, overexpressed TK1 mRNA triggered ssDNA release, restoring Cy5 fluorescence for imaging and enabling Dox release for chemotherapy.
- The nanosystem demonstrated low fluorescence and drug release in normal cells, highlighting its cancer-specific targeting capability.
Conclusions:
- The rationally designed nucleic acid-gated COF nanosystem achieves cancer-specific diagnostic imaging and drug release.
- This smart nanosystem offers a promising universal platform for cancer theranostics.
- The study presents a novel strategy for controlling COF-biomolecule interactions for advanced nanomedicine applications.
