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Published on: May 17, 2022
Nitric Oxide-Activated "Dual-Key-One-Lock" Nanoprobe for in Vivo Molecular Imaging and High-Specificity Cancer
Lili Teng1, Guosheng Song1, Yongchao Liu1
1Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering , Hunan University , Changsha 410082 , P. R. China.
Abstract:
Cancer treatments are confounded by severe toxic effects toward patients. To address these issues, activatable nanoprobes have been designed for specific imaging and destruction of cancer cells under the stimulation of specific cancer-associated biomarkers. Most activatable nanoprobes were usually activated by some single-factor stimulation, but this restricts therapeutic specificity between diseased and normal tissue; therefore, multifactor activation is highly desired. To this end, we herein develop a novel dual-stimuli responsive theranostic nanoprobe for simultaneously activatable cancer imaging and photothermal therapy under the coactivation of "dual-key" stimulation of "nitric oxide (NO)/acidity", so as to further improve the therapeutic specificity. Specifically, we have integrated a weak electron acceptor (benzo[c][1,2,5]thiadiazole-5,6-diamine) into a donor-π-acceptor-π-donor type chromophore. When the weak acceptor was oxidized by NO in acidic conditions to form a stronger acceptor (5H-[1,2,3]triazolo[4,5-f]-2,1,3-benzothiadiazole), the molecule absorption was significantly increased in the near-infrared region, based on the intramolecular charge transfer (ICT) mechanism. Under the dual-key stimulation of NO/acidity within the tumor associated with inflammation, the nanoprobe can correspondingly output dual signals for ratiometric photoacoustic and photothermal imaging of cancer in vivo and do so with enhanced accuracy and specificity. Our novel nanoprobe exhibited higher photoacoustic signal enhancement under dual-factor activation at 9.8 times that of NO and 132 times that of acidity alone, respectively. Moreover, through such dual activation of NO/acidity, the nanoprobe produces more differentiation of hyperthermia between tumor and normal tissues, to afford satisfactory photothermal therapy with minimal toxic side effects. Thus, our work presents a promising strategy for significantly improving the precision and specificity of cancer imaging and therapy.
Insights
This study introduces a novel dual-stimuli responsive nanoprobe for enhanced cancer imaging and photothermal therapy. Activated by nitric oxide (NO) and acidity, it improves therapeutic specificity and reduces side effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Cancer treatments face challenges due to severe toxic effects.
- Activatable nanoprobes offer targeted cancer imaging and destruction.
- Current nanoprobes activated by single factors lack specificity.
Purpose of the Study:
- To develop a dual-stimuli responsive theranostic nanoprobe for enhanced cancer imaging and photothermal therapy.
- To improve therapeutic specificity by coactivating nanoprobes with nitric oxide (NO) and acidity.
- To create a nanoprobe with improved accuracy and reduced side effects in cancer treatment.
Main Methods:
- Integrated a weak electron acceptor into a donor-π-acceptor-π-donor chromophore.
- Designed a nanoprobe activated by dual stimuli: nitric oxide (NO) and acidity.
- Utilized intramolecular charge transfer (ICT) mechanism for near-infrared absorption enhancement.
Main Results:
- The nanoprobe exhibited significantly increased absorption in the near-infrared region under dual NO/acidity stimulation.
- Achieved 9.8-fold signal enhancement from NO and 132-fold from acidity alone.
- Demonstrated enhanced differentiation of hyperthermia between tumor and normal tissues, leading to effective photothermal therapy with minimal toxicity.
Conclusions:
- The developed dual-stimuli responsive nanoprobe shows promise for precise cancer imaging and therapy.
- Coactivation by NO and acidity significantly improves specificity and reduces off-target toxic effects.
- This strategy offers a novel approach for advancing theranostic applications in oncology.
