Gold nanorod–assisted theranostic solution for nonvisible residual disease in bladder cancer

Author:

Armanetti Paolo1ORCID,Locatelli Irene23ORCID,Venegoni Chiara23ORCID,Alchera Elisa23,Campanella Beatrice4,Pederzoli Filippo235ORCID,Maturi Mirko6,Locatelli Erica6ORCID,Tortorella Silvia6ORCID,Curnis Flavio7ORCID,Corti Angelo7ORCID,Lucianò Roberta8,Onor Massimo4ORCID,Salonia Andrea235ORCID,Montorsi Francesco235ORCID,Moschini Marco23,Popov Viktor9,Jose Jithin10ORCID,Comes Franchini Mauro6ORCID,Ooi Ean Hin11ORCID,Menichetti Luca1ORCID,Alfano Massimo23ORCID

Affiliation:

1. National Council of Research-Institute of Clinical Physiology, Pisa 56124, Italy

2. Division of Experimental Oncology, Urological Research Institute (URI), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan 20132, Italy

3. Department of Urology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan 20132, Italy

4. National Research Council (CNR), Institute of Chemistry of Organometallic Compounds, Pisa 56124, Italy

5. Università Vita-Salute San Raffaele, Milan 20132, Italy

6. Department of Industrial Chemistry, Toso Montanari, University of Bologna, Bologna 40129, Italy

7. Division of Experimental Oncology, Tumor Biology and Vascular Targeting Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan 20132, Italy

8. Department of Pathology, Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan 20132, Italy

9. Ascend Technologies Ltd, Southampton SO15 2BG, Hampshire, United Kingdom

10. FUJIFILM Visualsonics Inc., Amsterdam AB 1114, The Netherlands

11. Medical Engineering and Technology Hub, School of Engineering, Monash University Malaysia, Selangor 47500, Malaysia

Abstract

Residual nonvisible bladder cancer after proper treatment caused by technological and therapeutic limitations is responsible for tumor relapse and progression. This study aimed to demonstrate the feasibility of a solution for simultaneous detection and treatment of bladder cancer lesions smaller than one millimeter. The α5β1 integrin was identified as a specific marker in 81% of human high-grade nonmuscle invasive bladder cancers and used as a target for the delivery of targeted gold nanorods (GNRs). In a preclinical model of orthotopic bladder cancer expressing the α5β1 integrin, the photoacoustic imaging of targeted GNRs visualized lesions smaller than one millimeter, and their irradiation with continuous laser was used to induce GNR-assisted hyperthermia. Necrosis of the tumor mass, improved survival, and computational modeling were applied to demonstrate the efficacy and safety of this solution. Our study highlights the potential of the GNR-assisted theranostic strategy as a complementary solution in clinical practice to reduce the risk of nonvisible residual bladder cancer after current treatment. Further validation through clinical studies will support the findings of the present study.

Funder

EC | Horizon 2020 Framework Programme

EC | HORIZON EUROPE Framework Programme

Publisher

Proceedings of the National Academy of Sciences

Reference45 articles.

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3. European Association of Urology Non-muscle-invasive Bladder Cancer Chapter 5: Diagnosis. https://uroweb.org/guidelines/non-muscle-invasive-bladder-cancer/chapter/diagnosis. Accessed 1 June 2014.

4. Clinical rationale and safety of restaging transurethral resection in indication-stratified patients with high-risk non-muscle-invasive bladder cancer

5. A randomized trial of PHOTOdynamic surgery in non–muscle-invasive bladder cancer;Rakesh Heer R. L.;NEJM Evid.,2022

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