A Smart Intracellular Self-Assembling Bioorthogonal Raman Active Nanoprobe for Targeted Tumor Imaging.

Autor: Tanwar S; Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA., Ghaemi B; The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA., Raj P; Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA., Singh A; The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Inc., Baltimore, MD, 21205, USA., Wu L; Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA., Yuan Y; Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui, 230026, China., Arifin DR; The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA., McMahon MT; The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Inc., Baltimore, MD, 21205, USA., Bulte JWM; The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Inc., Baltimore, MD, 21205, USA.; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.; Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.; Department of Oncology, Johns Hopkins University, Baltimore, MD, 21231, USA., Barman I; Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.; The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.; Department of Oncology, Johns Hopkins University, Baltimore, MD, 21231, USA.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2023 Dec; Vol. 10 (34), pp. e2304164. Date of Electronic Publication: 2023 Sep 15.
DOI: 10.1002/advs.202304164
Abstrakt: Inspired by the principle of in situ self-assembly, the development of enzyme-activated molecular nanoprobes can have a profound impact on targeted tumor detection. However, despite their intrinsic promise, obtaining an optical readout of enzyme activity with high specificity in native milieu has proven to be challenging. Here, a fundamentally new class of Raman-active self-assembling bioorthogonal enzyme recognition (nanoSABER) probes for targeted tumor imaging is reported. This class of Raman probes presents narrow spectral bands reflecting their vibrational fingerprints and offers an attractive solution for optical imaging at different bio-organization levels. The optical beacon harnesses an enzyme-responsive peptide sequence, unique tumor-penetrating properties, and vibrational tags with stretching frequencies in the cell-silent Raman window. The design of nanoSABER is tailored and engineered to transform into a supramolecular structure exhibiting distinct vibrational signatures in presence of target enzyme, creating a direct causality between enzyme activity and Raman signal. Through the integration of substrate-specific for tumor-associated enzyme legumain, unique capabilities of nanoSABER for imaging enzyme activity at molecular, cellular, and tissue levels in combination with machine learning models are shown. These results demonstrate that the nanoSABER probe may serve as a versatile platform for Raman-based recognition of tumor aggressiveness, drug accumulation, and therapeutic response.
(© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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