A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods
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Published:2023-08-27
Issue:1
Volume:21
Page:
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ISSN:1477-3155
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Container-title:Journal of Nanobiotechnology
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language:en
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Short-container-title:J Nanobiotechnol
Author:
Alfano Massimo, Alchera Elisa, Sacchi Angelina, Gori Alessandro, Quilici Giacomo, Locatelli Irene, Venegoni Chiara, Lucianò Roberta, Gasparri Anna Maria, Colombo Barbara, Taiè Giulia, Jose Jithin, Armanetti Paolo, Menichetti Luca, Musco Giovanna, Salonia Andrea, Corti AngeloORCID, Curnis FlavioORCID
Abstract
Abstract
Background
Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments.
Results
In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRs@PEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism.
Conclusion
GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions.
Graphical Abstract
Funder
European Union’s Horizon 2020 Ministero della Salute
Publisher
Springer Science and Business Media LLC
Subject
Pharmaceutical Science,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,Medicine (miscellaneous),Bioengineering
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