Long-Term In Vivo Fluorescence Analyses and Imaging-Guided Tumor Surgery in the Second Near-Infrared Window Using a Supramolecular Metallacage

Yi Qin , Niu Niu , Xue Li , Xueke Yan , Shuai Lu , Zhikai Li , Yixiong Gui , Jun-Long Zhu , Lin Xu , Xiaopeng Li , Dong Wang , Ben Zhong Tang

Aggregate ›› 2025, Vol. 6 ›› Issue (3) : e708

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Aggregate ›› 2025, Vol. 6 ›› Issue (3) : e708 DOI: 10.1002/agt2.708
RESEARCH ARTICLE

Long-Term In Vivo Fluorescence Analyses and Imaging-Guided Tumor Surgery in the Second Near-Infrared Window Using a Supramolecular Metallacage

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Abstract

Long-term in vivo fluorescence analysis is growing into a sparkling frontier in gaining deep insights into various biological processes. Exploration of such fluorophores with high performance still remains an appealing yet significantly challenging task. In this study, we have elaborately integrated a second near-infrared (NIR-II) emissive fluorophore with the metal Pt into a self-assembled prism-like metallacage M-DBTP, which enables the intravital long-term tracking of the metal Pt through NIR-II fluorescence imaging technologies. In addition, the intravital bioimaging of the metallacage-loaded nanoparticles (NPs) indicated an extraordinary photographic performance on the mice blood vessels and the rapid clearance of M-DBTP NPs from the blood within 7 h. The subsequent transfer to the bones and the retention of NPs in the bone marrow region for up to 35 days was revealed by long-term fluorescence analysis, which was confirmed by the distribution and metabolism of Pt through an inductively coupled plasma optical emission spectrometer. Moreover, the bright emission of M-DBTP NPs in the NIR-II region enables them to well perform on fluorescence imaging-guided tumor surgery.

Keywords

fluorescence imaging-guided tumor surgery / long-term fluorescence analysis / NIR-II fluorescence imaging / supramolecular metallacage

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Yi Qin, Niu Niu, Xue Li, Xueke Yan, Shuai Lu, Zhikai Li, Yixiong Gui, Jun-Long Zhu, Lin Xu, Xiaopeng Li, Dong Wang, Ben Zhong Tang. Long-Term In Vivo Fluorescence Analyses and Imaging-Guided Tumor Surgery in the Second Near-Infrared Window Using a Supramolecular Metallacage. Aggregate, 2025, 6(3): e708 DOI:10.1002/agt2.708

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References

[1]

(a) P. Pei, Y. Chen, C. Sun, et al., “X-ray-activated Persistent Luminescence Nanomaterials for NIR-II Imaging,” Nature Nanotechnology 16 (2021): 1011-1018. (b) L. Wu, J. Huang, K. Pu, and T. D. James, “Dual-Locked Spectroscopic Probes for Sensing and Therapy,” Nature Reviews Chemistry 5 (2021): 406-421. (c) J. Huang, X. Chen, Y. Jiang, et al., “Renal Clearable Polyfluorophore Nanosensors for Early Diagnosis of Cancer and Allograft Rejection,” Nature Materials 21 (2022): 598-607. (d) S. Zeng, X. Liu, Y. S. Kafuti, et al., “Fluorescent Dyes Based on Rhodamine Derivatives for Bioimaging and Therapeutics: Recent Progress, Challenges, and Prospects,” Chemical Society Reviews 52 (2023): 5607-5651. (e) F. Hu, S. Xu, and B. Liu, “Photosensitizers With Aggregation-Induced Emission: Materials and Biomedical Applications,” Advanced Materials 30 (2018): 1801350. (f) F. A. Oliveira, M. P. Nucci, I. S. Filgueiras, et al., “Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model,” Cells 9 (2020): 939.

[2]

(a) C. Zhou, Z. Li, Z. Zhu, et al., “Conjugated Oligoelectrolytes for Long-Term Tumor Tracking With Incremental NIR-II Emission,” Advanced Materials 34 (2022): 2201989. (b) C. Jin, G. Li, X. Wu, et al., “Robust Packing of a Self-Assembling Iridium Complex via Endocytic Trafficking for Long-Term Lysosome Tracking,” Angewandte Chemie International Edition 60 (2021): 7597-7601. (c) V. P. Nguyen, W. Fan, T. Zhu, et al., “Long-Term, Noninvasive in Vivo Tracking of Progenitor Cells Using Multimodality Photoacoustic, Optical Coherence Tomography, and Fluorescence Imaging,” ACS Nano 15 (2021): 13289-13306. (d) Y. Xu, R. Xu, Z. Wang, et al., “Recent Advances in Luminescent Materials for Super-Resolution Imaging via Stimulated Emission Depletion Nanoscopy,” Chemical Society Reviews 50 (2021): 667-690. (e) S. Koo, E. J. Lee, H. Xiong, et al., “Synthesis of Stereocontrolled Degradable Polymer by Living Cascade Enyne Metathesis Polymerization,” Angewandte Chemie International Edition 62 (2023): e202318459. (f) Z. Ye, W. Yang, Y. Zheng, et al., “Integrating a Far-Red Fluorescent Probe With a Microfluidic Platform for Super-Resolution Imaging of Live Erythrocyte Membrane Dynamics,” Angewandte Chemie International Edition 61 (2022): e202211540. (g) J. Wang, J. Song, X. Zhang, et al., “DNA-Programed Plasmon Rulers Decrypt Single-Receptor Dimerization on Cell Membrane,” Journal of the American Chemical Society 145 (2023): 1273-1284. (h) H. Zhang, L. Shi, K. Li, et al., “Discovery of an Ultra-Rapid and Sensitive Lysosomal Fluorescence Lipophagy Process,” Angewandte Chemie International Edition 61 (2022): e202116439.

[3]

(a) P. M. Takahara, A. C. Rosenzweig, C. A. Frederick, and S. J. Lippard, “Crystal Structure of Double-stranded DNA Containing the Major Adduct of the Anticancer Drug Cisplatin,” Nature 377 (1995): 649-652. (b) C. A. Rabik and M. E. Dolan, “Molecular Mechanisms of Resistance and Toxicity Associated With Platinating Agents,” Cancer Treatment Reviews 33 (2007): 9-23. (c) S. Dasari and P. B. Tchounwou, “Cisplatin in Cancer Therapy: Molecular Mechanisms of Action,” European Journal of Pharmacology 740 (2014): 364-378. (d) C. Li, Y. Pang, Y. Xu, et al., “Near-Infrared Metal Agents Assisting Precision Medicine: From Strategic Design to Bioimaging and Therapeutic Applications,” Chemical Society Reviews 52 (2023): 4392-4442. (e) X. Wang, X. Wang, S. Jin, N. Muhammad, and Z. Guo, “Stimuli-Responsive Therapeutic Metallodrugs,” Chemical Reviews 119 (2019): 1138-1192.

[4]

(a) X. Xue, C. Qian, H. Fang, et al., “Photoactivated Lysosomal Escape of a Monofunctional Pt II Complex Pt-BDPA for Nucleus Access,” Angewandte Chemie International Edition 58 (2019): 12661-12666. (b) L.-Y. Liu, H. Fang, Q. Chen, et al., “Multiple-Color Platinum Complex With Super-Large Stokes Shift for Super-Resolution Imaging of Autolysosome Escape,” Angewandte Chemie International Edition 59 (2020): 19229-19236. (c) K. Xiong, C. Ouyang, J. Liu, et al., “Chiral Ru II - Pt II Complexes Inducing Telomere Dysfunction Against Cisplatin-Resistant Cancer Cells,” Angewandte Chemie International Edition 61 (2022): 202204866. (d) B.-B. Liang, Q. Liu, B. Liu, et al., “A Golgi-Targeted Platinum Complex Plays a Dual Role in Autophagy Regulation for Highly Efficient Cancer Therapy,” Angewandte Chemie International Edition 62 (2023): e202312170. (e) E. M. Bolitho, C. Sanchez-Cano, H. Shi, et al., “Single-Cell Chemistry of Photoactivatable Platinum Anticancer Complexes,” Journal of the American Chemical Society 143 (2021): 20224-20240.

[5]

(a) A. L. Antaris, H. Chen, K. Cheng, et al., “A Small-Molecule Dye for NIR-II Imaging,” Nature Materials 15 (2016): 235-242. (b) A. Ji, H. Lou, C. Qu, et al., “Acceptor Engineering for NIR-II Dyes With High Photochemical and Biomedical Performance,” Nature Communications 13 (2022): 3815. (c) Z. Lei and F. Zhang, “Molecular Engineering of NIR-II Fluorophores for Improved Biomedical Detection,” Angewandte Chemie International Edition 60 (2021): 16294-16308. (d) J. Mu, M. Xiao, Y. u Shi, et al., “The Chemistry of Organic Contrast Agents in the NIR-II Window,” Angewandte Chemie International Edition 61 (2022): e202114722. (e) Y. Fang, J. Shang, D. Liu, W. Shi, X. Li, and H. Ma, “Design, Synthesis, and Application of a Small Molecular NIR-II Fluorophore With Maximal Emission Beyond 1200 nm,” Journal of the American Chemical Society 142 (2020): 15271-15275. (f) Z. Feng, Y. Li, S. Chen, et al., “Engineered NIR-II Fluorophores With Ultralong-Distance Molecular Packing for High-Contrast Deep Lesion Identification,” Nature Communications 14 (2023): 5017.

[6]

(a) E. G. Percastegui, T. K. Ronson, and J. R. Nitschke, “Design and Applications of Water-Soluble Coordination Cages,” Chemical Reviews 120 (2020): 13480-13544. (b) L.-J. Chen and H.-B. Yang, “Construction of Stimuli-Responsive Functional Materials via Hierarchical Self-Assembly Involving Coordination Interactions,” Accounts of Chemical Research 51 (2018): 2699-2710. (c) Y. Xu, Y. Dou, Q. Li, et al., “When Near-Infrared Fluorescence Meets Supramolecular Coordination Complexes: Challenges and Opportunities of Metallacycles/Metallacages in Precision Biomedicine,” Coordination Chemistry Reviews 493 (2023): 215320. (d) X.-Z. Li, C.-B. Tian, and Q.-F. Sun, “Coordination-Directed Self-Assembly of Functional Polynuclear Lanthanide Supramolecular Architectures,” Chemical Reviews 122 (2022): 6374-6458. (e) W.-T. Dou, C.-Y. Yang, L.-R. Hu, et al., “Metallacages and Covalent Cages for Biological Imaging and Therapeutics,” ACS Materials Letters 5 (2023): 1061-1082.

[7]

(a) L. Tu, C. Li, X. Xiong, et al., “Engineered Metallacycle-Based Supramolecular Photosensitizers for Effective Photodynamic Therapy,” Angewandte Chemie International Edition 62 (2023): e202301560. (b) G. Yu, S. Yu, M. L. Saha, et al., “A Discrete Organoplatinum(II) Metallacage as a Multimodality Theranostic Platform for Cancer Photochemotherapy,” Nature Communications 9 (2018): 4335. (c) Y. Qin, X. Chen, Y. Gui, H. Wang, B. Z. Tang, and D. Wang, “Self-Assembled Metallacage With Second Near-Infrared Aggregation-Induced Emission for Enhanced Multimodal Theranostics,” Journal of the American Chemical Society 144 (2022): 12825-12833. (d) H. Zhu, L. Pesce, R. Chowdhury, et al., “Stereocontrolled Self-Assembly of a Helicate-Bridged Cu I12 L 4 Cage That Emits Circularly Polarized Light,” Journal of the American Chemical Society 146 (2024): 2379-2386. (e) K. Wu, E. Benchimol, A. Baksi, and G. H. Clever, “Non-Statistical Assembly of Multicomponent [Pd2ABCD] Cages,” Nature Chemistry 16 (2024): 584-591. (f) Y.-H. Huang, Y.-L. Lu, J. Ruan, et al., “Dynamic Metallosupramolecular Cages Containing 12 Adaptable Pockets for High-order Guest Binding Beyond Biomimicry,” Journal of the American Chemical Society 145 (2023): 23361-23371. (g) C. Mu, L. Zhang, G. Li, et al., “Isoreticular Preparation of Tetraphenylethylene-based Multicomponent Metallacages Towards Light-Driven Hydrogen Production,” Angewandte Chemie International Edition 62 (2023): e202311137. (h) D.-N. Yan, L.-X. Cai, P.-M. Cheng, S.-J. Hu, L.-P. Zhou, and Q.-F. Sun, “Photooxidase Mimicking With Adaptive Coordination Molecular Capsules,” Journal of the American Chemical Society 143 (2021): 16087-16094. (i) L.-J. Chen, S. J. Humphrey, J.-L. Zhu, et al., “A Two-Dimensional Metallacycle Cross-Linked Switchable Polymer for Fast and Highly Efficient Phosphorylated Peptide Enrichment,” Journal of the American Chemical Society 143 (2021): 8295-8304. (j) V. A. Rinshad, J. Sahoo, M. Venkateswarulu, N. Hickey, M. De, and P. S. Mukherjee, “Solvent Induced Conversion of a Self-Assembled Gyrobifastigium to a Barrel and Encapsulation of Zinc-Phthalocyanine Within the Barrel for Enhanced Photodynamic Therapy,” Angewandte Chemie International Edition 62 (2023): e202218226.

[8]

Y. Sun, C. Chen, J. Liu, and P. J. Stang, “Recent Developments in the Construction and Applications of Platinum-Based Metallacycles and Metallacages via Coordination,” Chemical Society Reviews 49 (2020): 3889-3919.

[9]

(a) J. Mei, N. L. C. Leung, R. T. K. Kwok, J. W. Y. Lam, and B. Z. Tang, “Aggregation-Induced Emission: Together We Shine, United We Soar!,” Chemical Reviews 115 (2015): 11718-11940. (b) D. Yan, M. Wang, Q. Wu, et al., “Multimodal Imaging-Guided Photothermal Immunotherapy Based on a Versatile NIR-II Aggregation-Induced Emission Luminogen,” Angewandte Chemie International Edition 61 (2022): e202202614. (c) D. Yan, T. Li, Y. Yang, et al., “A Water-Soluble AIEgen for Noninvasive Diagnosis of Kidney Fibrosis via SWIR Fluorescence and Photoacoustic Imaging,” Advanced Materials 34 (2022): 2206643. (d) D. Yan, Y. Huang, J. Zhang, et al., “Adding Flying Wings: Butterfly-Shaped NIR-II AIEgens With Multiple Molecular Rotors for Photothermal Combating of Bacterial Biofilms,” Journal of the American Chemical Society 145 (2023): 25705-25715. (e) S. Song, Y. Wang, Y. Zhao, et al., “Molecular Engineering of AIE Luminogens for NIR-II/IIb Bioimaging and Surgical Navigation of Lymph Nodes,” Matter 5 (2022): 2847-2863. (f) S. Song, Y. Zhao, M. Kang, et al., “An NIR-II Excitable AIE Small Molecule With Multimodal Phototheranostic Features for Orthotopic Breast Cancer Treatment,” Advanced Materials 36 (2024): 2309748. (g) J. Cui, F. Zhang, D. Yan, et al., ““Trojan Horse” Phototheranostics: Fine-Engineering NIR-II AIEgen Camouflaged by Cancer Cell Membrane for Homologous-Targeting Multimodal Imaging-Guided Phototherapy,” Advanced Materials 35 (2023): 2302639. (h) S. Deng, Z. Peng, F. Zhou, et al., “Elaborately Engineered Au(I)-Based AIEgens: Robust and Broad-Spectrum Elimination Abilities Toward Drug-Resistant Bacteria,” Aggregate 5 (2024): e575. (i) H. Yan, Y. He, D. Wang, T. Han, and B. Z. Tang, “Aggregation-Induced Emission Polymer Systems With Circularly Polarized Luminescence,” Aggregate 4 (2023): e331. (j) Y. Qin, X. Li, S. Lu, et al., “Modular Construction of AIE-Active Supramolecular Cages With Tunable Fluorescence for NIR-II Blood Vessel Imaging,” ACS Materials Letters 5 (2023): 1982-1991.

[10]

Z. Hu, L. Feng, and P. Yang, “2, 1, 3-Benzothiadiazole Derivative Small Molecule Fluorophores for NIR-II Bioimaging,” Advanced Functional Materials 34 (2024): 2310818.

[11]

(a) X. Chang, S. Lin, G. Wang, et al., “Self-Assembled Perylene Bisimide-Cored Trigonal Prism as an Electron-Deficient Host for C60 and C70 Driven by “like Dissolves like”,” Journal of the American Chemical Society 142 (2020): 15950-15960. (b) J. Yang, M. Bhadbhade, W. A. Donald, et al., “Self-Assembled Supramolecular Cages Containing Ruthenium (II) Polypyridyl Complexes,” Chemical Communications 51 (2015): 4465-4468.

[12]

Z. R. Grabowski, K. Rotkiewicz, and W. Rettig, “Structural Changes Accompanying Intramolecular Electron Transfer: Focus on Twisted Intramolecular Charge-Transfer States and Structures,” Chemical Reviews 103 (2003): 3899-4032.

[13]

(a) X. Yan, T. R. Cook, P. Wang, F. Huang, and P. J. Stang, “Highly Emissive Platinum(II) Metallacages,” Nature Chemistry 7 (2015): 342-348. (b) C. Mu, Z. Zhang, Y. Hou, et al., “Tetraphenylethylene-Based Multicomponent Emissive Metallacages as Solid-State Fluorescent Materials,” Angewandte Chemie International Edition 60 (2021): 12293-12297. (c) J.-G. Yu, L.-Y. Sun, C. Wang, Y. Li, and Y.-F. Han, “Coordination-Induced Emission From Tetraphenylethylene Units and Their Applications,” Chemistry – A European Journal 27 (2021): 1556-1575. (d) Y. Qin, Q.-H. Ling, Y.-T. Wang, et al., “Construction of Covalent Organic Cages With Aggregation-Induced Emission Characteristics From Metallacages for Mimicking Light-Harvesting Antenna,” Angewandte Chemie International Edition 62 (2023): e202308210.

[14]

(a) K.-W. Lee, Y. Gao, W.-C. Wei, et al., “Anti-Quenching NIR-II J-Aggregates of Benzo[c]Thiophene Fluorophore for Highly Efficient Bioimaging and Phototheranostics,” Advanced Materials 35 (2023): 2211632. (b) R. Wei, Y. Dong, X. Wang, et al., “Rigid and Photostable Shortwave Infrared Dye Absorbing/Emitting Beyond 1200 Nm for High-Contrast Multiplexed Imaging,” Journal of the American Chemical Society 145 (2023): 12013-12022. (c) Y. Li, Z. Cai, S. Liu, et al., “Design of AIEgens for Near-Infrared IIb Imaging Through Structural Modulation at Molecular and Morphological Levels,” Nature Communications 11 (2020): 1255. (d) C. Sun, B. Li, M. Zhao, et al., “J -Aggregates of Cyanine Dye for NIR-II in Vivo Dynamic Vascular Imaging Beyond 1500 nm,” Journal of the American Chemical Society 141 (2019): 19221-19225.

[15]

(a) Z. Xue, S. Zeng, and J. Hao, “Non-Invasive Through-Skull Brain Vascular Imaging and Small Tumor Diagnosis Based on NIR-II Emissive Lanthanide Nanoprobes Beyond 1500 Nm,” Biomaterials 171 (2018): 153-163. (b) X. Li, M. Jiang, S. Zeng, and H. Liu, “Polydopamine Coated Multifunctional Lanthanide Theranostic Agent for Vascular Malformation and Tumor Vessel Imaging Beyond 1500 Nm and Imaging-Guided Photothermal Therapy,” Theranostics 9 (2019): 3866-3878.

[16]

(a) D. Liu, Z. He, Y. Zhao, et al., “Xanthene-Based NIR-II Dyes for in Vivo Dynamic Imaging of Blood Circulation,” Journal of the American Chemical Society 143 (2021): 17136-17143. (b) M. Chen, Z. Feng, X. Fan, et al., “Long-Term Monitoring of Intravital Biological Processes Using Fluorescent Protein-Assisted NIR-II Imaging,” Nature Communications 13 (2022): 6643.

[17]

(a) D. Chen, Y. Liu, Z. Zhang, et al., “NIR-II Fluorescence Imaging Reveals Bone Marrow Retention of Small Polymer Nanoparticles,” Nano Letters 21 (2021): 798-805. (b) M. G. Bixel, A. P. Kusumbe, S. K. Ramasamy, et al., “Flow Dynamics and HSPC Homing in Bone Marrow Microvessels,” Cell Reports 18 (2017): 1804-1816.

[18]

(a) A. L. Vahrmeijer, M. Hutteman, J. R. van der Vorst, C. J. H. van de Velde, and J. V. Frangioni, “Image-Guided Cancer Surgery Using Near-Infrared Fluorescence,” Nature Reviews Clinical Oncology 10 (2013): 507-518. (b) C. Chen, X. Ni, H.-W. Tian, Q. Liu, D.-S. Guo, and D. Ding, “Calixarene-Based Supramolecular AIE Dots With Highly Inhibited Nonradiative Decay and Intersystem Crossing for Ultrasensitive Fluorescence Image-Guided Cancer Surgery,” Angewandte Chemie International Edition 59 (2020): 10008-10012.

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2024 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.

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