Urine-Stable Aptamer-Conjugated Gold Nanorods for the Early Detection of High-Grade Bladder Cancer Residual Disease

Abstract

The limitations of current diagnostic imaging techniques and therapies for bladder cancer are associated with and responsible for the recurrence and progression of residual disease, with an impact on social costs and quality of life of patients. This study delivers a cost-effective solution for the detection of bladder cancer residual disease, which is represented by the early detection of bladder cancer lesions < 1 mm. Urine-stable 34-mer SH-terminated 2'F-Py-RNA aptamer that recognizes the integrin α5β1, expressed by 81% of human high-grade non-muscle invasive bladder cancer, is developed. The intravesical instillation of aptamer-conjugated gold nanorods as contrast agent for photoacoustic imaging is validated in a preclinical model of orthotopic bladder cancer expressing the integrin α5β1. The photoacoustic signal of gold nanorods remains on the tumor surface for 3 h and allows early detection of cancer lesions < 1 mm. The aptamer is internalized into lysosomes, an opportunity that paves the way for lysosomal-mediated drug release in tumor cells. This study highlights the potential of urine-stable aptamer for the delivery of a solution to target the residual high-grade bladder cancer disease.

Keywords: aptamer; bladder cancer; detection; nanoparticles; urine.