Full Text | PDF

Theranostics 2024; 14(7):2675-2686. doi:10.7150/thno.92991 This issue Cite

Research Paper

Albumin-seeking dyes with adjustable assemblies in situ enable programmable imaging windows and targeting tumor imaging

Yijing Du^1,2, Jiajun Xu^1,2, Tianyang Han^1,2, Zijian Jiang¹, Yuewei Zhang³, Jia Li^1✉, Xiaoyuan Chen^4,5,6✉, Shoujun Zhu^1,2✉

1. Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, First Hospital of Jilin University, Jilin University, Changchun 130021, P.R. China.
2. State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P.R. China.
3. School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, P.R. China.
4. Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, 117597, Singapore, Singapore.
5. Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
6. Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Singapore.

✉ Corresponding authors: lijia0204edu.cn, chen.shawnedu.sg, sjzhuedu.cn.

Abstract

Cyanine dyes are widely used organic probes for in vivo imaging due to their tunable fluorescence. They can form complexes with endogenous albumin, resulting in enhanced brightness and photostability. However, this binding is uncontrollable and irreversible, leading to considerable nonspecific background signals and unregulated circulation time.

Methods: Here, we connect varying numbers of 4-(4-iodophenyl) butanoic acid (IP) as albumin-binding moieties (ABM) to the cyanine dye, enabling dynamic and controllable binding with albumin. Meanwhile, we provide a blocking method to completely release the dye from covalent capture with albumin, resulting in specific targeting fluorescence. Furthermore, we evaluate the pharmacokinetics and tumor targeting of the developed dyes.

Results: The engineered dyes can dynamically and selectively bind with multiple albumins to change the in situ size of assemblies and circulation time, providing programmable regulation over the imaging time window. The nucleophilic substitution of meso-Cl with water-soluble amino acids or targeting peptides for IP-engineered dye further addresses the nonspecific signals caused by albumin, allowing for adjustable angiography time and efficient tumor targeting.

Conclusion: This study rationalizes the binding modes of dyes and proteins, applicable to a wide range of near-infrared (NIR) dyes for improving their in vivo molecular imaging.

Keywords: Dynamic albumin binder, Programmable imaging windows, Dye@albumin nanoparticles, Protein pocket-escaping design, Tumor-targeting dyes

Citation styles

©2024 Ivyspring International Publisher. Terms of use