Novel Non-Invasive Diagnosis of Bladder Cancer in Urine Based on Multifunctional Nanoparticles

Objectives: Tumor cells were reported to have perpetual negative surface charges due to elevated glycolysis, and multifunctional nanoprobes (Fe₃O₄@SiO_2, mNPs) could attach onto tumor cells via opposite surface charges. We thus evaluated whether mixing mNPs with urine could improve the sensitivity of urine cytology test (UCT). Methods: We developed a novel UCT method by mixing urine with mNPs (Nano-cytology) to harvest more tumor cells during UCT procedures. The same voided urine sample was divided equally for the Nano-cytology and UCT assay, and evaluated by cytopathologists in a blinded way. The accuracy of UCT, Nano-cytology, and the combination of the two approaches (Nano-UCT) for detecting bladder cancer were determined. Results: Urine samples were prospectively collected from 102 bladder cancer patients and 49 non-cancer participants from June 2020 to February 2021 in Changhai Hospital. Overall sensitivity of the Nano-cytology assay was significantly higher than that of the UCT assay (82.4 vs. 59.8%, p < .01). Sensitivity for low- and high-grade tumors was 79.1% and 39.5% (p < .01) and 84.7% and 74.6% (p = .25) for Nano-cytology and UCT, respectively. Specificity of Nano-cytology was slightly lower than that of UCT (89.8% vs. 100%, p = .022), which is mainly caused by severe urinary tract infection. In addition, Nano-UCT showed increased sensitivity with 90.2% for overall patients, and 83.7% and 94.9% for low- and high-grade tumor, respectively. Conclusion: The Nano-cytology assay had a significantly improved sensitivity compared with UCT for detecting bladder cancer patients. It represents a promising tool for diagnosis of bladder cancer in clinical practice.