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Dual-Receptor Targeted Imaging of Cancer Cells with a Bioorthogonal Iridium(III)-Based Probe
Shaozhen Jing1,2, Jia Wu3, Kai Yang4
1Research & Development Institute of Northwestern Polytechnical University in Shenzhen, 45 South Gaoxin Road, Shenzhen 518057, China.
Abstract:
Luminescence probes targeting specific membrane receptors are powerful imaging tools for cancer detection and image-guided surgical navigation. However, conventional single receptor targeting probes often suffer from low specificity and high background interference, limiting their effectiveness in accurately imaging cancer cells. Herein, we developed two dual receptor-mediated luminescent iridium(III) complexes for precise cancer cell imaging using a bioorthogonal activation approach. We strategically designed these probes to target two different biomarkers on the membrane: the benzenesulfonamide group in the N^N ligand targets carbonic anhydrase IX (CAIX), while the biotin moiety linked to endo-9-hydroxymethyl-bicyclo[6.1.0]non-4-yne (BCN) targets the biotin receptor. Complexes 1 and 2 exhibit 16- and 29-fold luminescence enhancement after reacting with BCN-Biotin, with rapid second-order rate constants (k2) of 3.5 × 105 M-1 s-1 and 8.7 × 103 M-1 s-1, respectively. Notably, complex 2 can sensitively and specifically detect cancer cells overexpressing CAIX, as verified by multiple biochemical experiments. On the other hand, complex 2 showed negligible luminescence in cell lines with low expression of CAIX, demonstrating its ability to discriminate cancer cells. Overall, this work demonstrates the promising potential of dual receptor-mediated iridium(III) complexes based on the bioorthogonal activation strategy for the accurate and specific imaging of cancer cells.
Insights
New dual receptor-mediated luminescent iridium(III) complexes offer precise cancer cell imaging. These probes utilize bioorthogonal activation for enhanced specificity in detecting cancer biomarkers like carbonic anhydrase IX (CAIX).
Area of Science:
- Inorganic Chemistry
- Biomedical Imaging
- Chemical Biology
Background:
- Luminescence probes are vital for cancer detection and surgical navigation.
- Current probes targeting single receptors face challenges with specificity and background noise.
- Accurate imaging of cancer cells requires improved probe design.
Purpose of the Study:
- To develop novel dual receptor-mediated luminescent iridium(III) complexes for precise cancer cell imaging.
- To employ a bioorthogonal activation strategy for enhanced probe performance.
- To target carbonic anhydrase IX (CAIX) and biotin receptors for specific cancer cell detection.
Main Methods:
- Design and synthesis of two dual receptor-mediated luminescent iridium(III) complexes.
- Incorporation of benzenesulfonamide for CAIX targeting and BCN-biotin for biotin receptor targeting.
- Evaluation of luminescence enhancement, reaction kinetics, and specificity in cancer cell lines.
Main Results:
- Complexes 1 and 2 showed significant luminescence enhancement (16- and 29-fold) upon bioorthogonal reaction.
- Rapid second-order rate constants (k2) were determined for the probe activation.
- Complex 2 demonstrated sensitive and specific detection of CAIX-overexpressing cancer cells with minimal signal in low-CAIX cells.
Conclusions:
- Dual receptor-mediated iridium(III) complexes with bioorthogonal activation show promise for accurate cancer cell imaging.
- This strategy enhances probe specificity and reduces background interference.
- The developed probes offer a potential advancement in cancer diagnostics and image-guided surgery.
