Enzyme-activated probes in optical imaging: a focus on atherosclerosis

Walter, Edward R. H.; Cooper, Saul M.; Boyle, Joseph J.; Long, Nicholas J.

doi:10.1039/d1dt02198b

Cited by 19 publications

(14 citation statements)

References 98 publications

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“…As an essential product of the tumor interstitial inflammatory reaction, fibronectin is significantly overexpressed and correlates well with tumor fibrosis and infiltration [ 29 ]. MMP-9-activatable imaging probes have been successfully applied for specific imaging of cancer [ 30 ] and targeted anticancer drug delivery systems [ 25 ]. Fibronectin-targeted CREKA-based imaging probes have been widely applied in cancer diagnosis and treatment [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Fibronectin-targeting and metalloproteinase-activatable smart imaging probe for fluorescence imaging and image-guided surgery of breast cancer

Cheng

Jin

et al. 2023

J Nanobiotechnol

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Residual lesions in the tumor bed have been a challenge for conventional white-light breast-conserving surgery. Meanwhile, lung micro-metastasis also requires improved detection methods. Intraoperative accurate identification and elimination of microscopic cancer can improve surgery prognosis. In this study, a smart fibronectin-targeting and metalloproteinase-activatable imaging probe CREKA-GK8-QC is developed. CREKA-GK8-QC possesses an average diameter of 21.7 ± 2.5 nm, excellent MMP-9 protein responsiveness and no obvious cytotoxicity. In vivo experiments demonstrate that NIR-I fluorescence imaging of CREKA-GK8-QC precisely detects orthotopic breast cancer and micro-metastatic lesions (nearly 1 mm) of lungs with excellent imaging contrast ratio and spatial resolution. More notably, fluorescence image-guided surgery facilitates complete resection and avoids residual lesions in the tumor bed, improving survival outcomes. We envision that our newly developed imaging probe shows superior capacity for specific and sensitive targeted imaging, as well as providing guidance for accurate surgical resection of breast cancer. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Fibronectin-targeting and metalloproteinase-activatable smart imaging probe for fluorescence imaging and image-guided surgery of breast cancer

Cheng

Jin

et al. 2023

J Nanobiotechnol

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“…When inflammation occurs, macrophages are activated to secrete large amounts of proteases such as cathepsin, thrombin, and matrix metalloproteinases (MMPs) including myeloperoxidase and heme oxygenase-1, into the pathological microenvironments of atherosclerotic plaques to enhance collagen degradation and erosion of fibrous caps and increase the risk of plaque rupture. [206,207] Therefore, it is highly urgent to develop enzyme-responsive probes for the diagnosis and treatment of high-risk atherosclerotic plaques. For example, Ogawa et al developed a cysteine lysosomal hydrolase (cathepsin B)-responsive Peptide-ICG2 FL probe for NIR FL imaging of vulnerable atherosclerotic plaques.…”

Section: Enzyme Responsivenessmentioning

confidence: 99%

Biomarker‐Responsive Nanosystems for Chronic Disease Theranostics

Wang

et al. 2022

Adv Funct Materials

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Chronic diseases claim millions of lives every year, and it is of great significance to explore and develop advanced drugs to improve the cure rate of chronic diseases. Nanotheranostics are innovative strategies that enable the integration of diagnostic and therapeutic properties into a single nanosystem. Despite great success in nanotheranostics, their applications of nanotheranostics in nanomedicine are still in their infancy. This is because each disease has its corresponding characteristic pathological microenvironment, which motivates the development of endogenous biomarker-responsive nanosystems to meet the requirements of diagnosis and treatment. Herein, recent progress is presented in biomarker-responsive nanosystems and their biomedical applications. First, biomarker-responsive nanosystems are classified into eight subsections according to the type of chronic diseases, including tumors, cardiovascular diseases, neurological diseases, Wilson's diseases, chronic liver diseases, chronic kidney diseases, diabetes mellitus, and rheumatoid arthritis. In the following, a variety of intriguing applications of biomarkers-responsive nanosystems are briefly elaborated, such as biosensing, diagnosis, therapy, combined theranostics, and early evaluation of therapy effect, etc. Finally, the challenges and future directions from research to clinical translation of these responsive nanosystems are also presented.

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“…An alternative approach is based on cleavable probes, which are MMP substrates rather than inhibitors. Cleavable probes can be considered as analogues of activatable probes such as those frequently used to detect protease activity by OI [reviewed in [86]]. The advantage of the cleavable approach is signal amplification, as many copies of the probes can be processed per unit time.…”

Section: Mri Probes To Image Ecm Enzymesmentioning

confidence: 99%

Extracellular Matrix Targeted MRI Probes

et al. 2022

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Dysregulated remodeling of the extracellular matrix (ECM) can lead to excessive accumulation of ECM proteins (primarily collagen, elastin/ tropoelastin, fibronectin and fibrin) resulting in tissue fibrosis. In many pathologies, changes in the molecular pattern of ECM components have been related to the progression and severity of fibrosis. Thus, magnetic resonance imaging (MRI) probes sensing specific ECM components hold promise for accurate staging of fibrotic diseases. This paper focuses on gadolinium-based contrast agents (GBCA) targeted to ECM components, including structural proteins and enzymes. According to available examples, they can be grouped into: 1) GBCA conjugated to targeting vectors that recognize and noncovalently bind to specific sites on the molecular target; 2) GBCA carrying a reactive chemical function able to bind covalently to the complementary chemical function of the molecular target; and 3) enzyme-responsive probes, whose relaxivity and pharmacokinetics change after enzymatic processing. Pros and cons of each approach are discussed.

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Enzyme-activated probes in optical imaging: a focus on atherosclerosis

Abstract: Enzyme-activated probes enable complex biological processes to be studied in real-time. A wide range of enzymes are modulated in diseases, including cancer, inflammatory diseases and cardiovascular disease, and have the...

Cited by 19 publications

References 98 publications

Fibronectin-targeting and metalloproteinase-activatable smart imaging probe for fluorescence imaging and image-guided surgery of breast cancer

Fibronectin-targeting and metalloproteinase-activatable smart imaging probe for fluorescence imaging and image-guided surgery of breast cancer

Biomarker‐Responsive Nanosystems for Chronic Disease Theranostics

Extracellular Matrix Targeted MRI Probes

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