Furin‐Mediated Self‐Assembly of Olsalazine Nanoparticles for Targeted Raman Imaging of Tumors

Olsalazine (Olsa) is a broad‐spectrum anti‐cancer agent acting as a DNA‐methylation inhibitor. When conjugated to 2‐cyano‐6‐aminobenzothiazole and a peptide substrate specific for the tumor‐overexpressed enzyme furin, it can self‐assemble into nanoparticles that can be detected by chemical‐exchange...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2021-02, Vol.60 (8), p.3923-3927
Main Authors: Yuan, Yue, Raj, Piyush, Zhang, Jia, Siddhanta, Soumik, Barman, Ishan, Bulte, Jeff W. M.
Format: Article
Language:English
Subjects:
Aminobenzothiazoles
Aminosalicylic Acids - chemistry
Animals
Contrast Media - chemistry
DNA methylation
Furin
HCT116 Cells
Humans
Magnetic resonance imaging
Magnetic Resonance Imaging - methods
Medical imaging
Mice
Mice, SCID
Microscopy, Fluorescence
Nanoparticles
Nanoparticles - chemistry
Neoplasms - diagnostic imaging
Neoplasms - pathology
olsalazine
Raman spectroscopy
self-assembly
Spectroscopy
Spectrum analysis
Spectrum Analysis, Raman
Substrates
Surgery
Transplantation, Heterologous
Tumor cells
Tumors
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Summary:Olsalazine (Olsa) is a broad‐spectrum anti‐cancer agent acting as a DNA‐methylation inhibitor. When conjugated to 2‐cyano‐6‐aminobenzothiazole and a peptide substrate specific for the tumor‐overexpressed enzyme furin, it can self‐assemble into nanoparticles that can be detected by chemical‐exchange saturation‐transfer magnetic‐resonance imaging (CEST MRI). We report here that these nano‐assemblies can also be detected with high specificity in furin‐overexpressing tumor cells by Raman spectroscopy with a distinct scattering signature and demonstrate the utility of this sensing mechanism in vitro and in vivo. Our findings suggest that Raman spectroscopy could be used for high‐resolution image‐guided surgery to precisely delineate tumor margins during and after resection in real‐time as well as to determine microscopic tumor invasion and multifocal locoregional tumor spread, which are currently impossible to visualize with available imaging technologies, including CEST MRI. Based on a furin‐mediated CBT‐Cys click condensation reaction followed by intracellular nanoparticle self‐assembly, we report the development of a new furin‐specific Raman reporter Olsa‐RVRR and demonstrate its in‐vitro and in‐vivo utility in tumor detection.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202014839