A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods.

Autor: Alfano M; Unit of Urology, URI, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Alchera E; Unit of Urology, URI, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Sacchi A; Tumor Biology and Vascular Targeting Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy., Gori A; Istituto di Scienze e Tecnologie Chimiche, C.N.R., Milan, Italy., Quilici G; Biomolecular NMR Laboratory, IRCCS San Raffaele Scientific Institute, Milan, Italy., Locatelli I; Unit of Urology, URI, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Venegoni C; Unit of Urology, URI, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Lucianò R; Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Gasparri AM; Tumor Biology and Vascular Targeting Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy., Colombo B; Tumor Biology and Vascular Targeting Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy., Taiè G; Tumor Biology and Vascular Targeting Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy., Jose J; FUJIFILM Visualsonics Inc, Amsterdam, The Netherlands., Armanetti P; Institute of Clinical Physiology, Italian National Research Council (CNR), Pisa, Italy., Menichetti L; Institute of Clinical Physiology, Italian National Research Council (CNR), Pisa, Italy., Musco G; Biomolecular NMR Laboratory, IRCCS San Raffaele Scientific Institute, Milan, Italy., Salonia A; Unit of Urology, URI, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Università Vita-Salute San Raffaele, Milan, Italy., Corti A; Tumor Biology and Vascular Targeting Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy. corti.angelo@hsr.it.; Università Vita-Salute San Raffaele, Milan, Italy. corti.angelo@hsr.it., Curnis F; Tumor Biology and Vascular Targeting Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy. curnis.flavio@hsr.it.
Jazyk: angličtina
Zdroj: Journal of nanobiotechnology [J Nanobiotechnology] 2023 Aug 27; Vol. 21 (1), pp. 301. Date of Electronic Publication: 2023 Aug 27.
DOI: 10.1186/s12951-023-02028-5
Abstrakt: 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.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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