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Author Spotlight: Tracking Electrochemistry on Single Nanoparticles with Surface-Enhanced Raman Scattering Spectroscopy and Microscopy
Published on: May 12, 2023
Surface-Enhanced Raman Scattering Nanoparticles for Multiplexed Imaging of Bladder Cancer Tissue Permeability and
Ryan M Davis, Bernhard Kiss1, Dharati R Trivedi1,2
1Department of Urology , Stanford University School of Medicine , Stanford , California 94305 , United States.
Abstract:
Bladder cancer has the highest recurrence rate of all cancers due in part to inadequate transurethral resection. Inadequate resection is caused by the inability of cystoscopes to detect invisible lesions during the resection procedure. To improve detection and resection of nonmuscle invasive bladder cancer, we quantified the ability of a surface-enhanced Raman nanoparticle and endoscope system to classify bladder tissue as normal or cancerous. Both antibody-based (active) and tissue permeability-based (passive) targeting mechanisms were evaluated by topically applying nanoparticles to ex vivo human bladder tissue samples. Multiplexed molecular imaging of CD47 and Carbonic Anhydrase 9 tumor proteins gave a receiver operating characteristic area under the curve (ROC AUC of 0.93 (0.75, 1.00). Furthermore, passively targeted nanoparticles enabled tissue classification with an ROC AUC of 0.93 (0.73, 1.00). Passively targeted nanoparticles penetrated 5-fold deeper and bound to tumor tissue at 3.3-fold higher concentrations in cancer compared to normal bladder urothelium, suggesting the existence of an enhanced surface permeability and retention effect in human bladder cancer.
Insights
This study introduces a novel nanoparticle system for enhanced bladder cancer detection. The system accurately distinguishes cancerous tissue, improving upon current cystoscope limitations for better surgical outcomes.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanotechnology
Background:
- Bladder cancer exhibits high recurrence rates, often due to incomplete transurethral resection.
- Current cystoscopes struggle to detect invisible lesions, leading to inadequate tumor removal.
- Improved diagnostic tools are crucial for nonmuscle invasive bladder cancer management.
Purpose of the Study:
- To evaluate a surface-enhanced Raman nanoparticle and endoscope system for classifying bladder tissue.
- To assess both active (antibody-based) and passive (tissue permeability-based) nanoparticle targeting mechanisms.
- To enhance the detection and resection of nonmuscle invasive bladder cancer.
Main Methods:
- Ex vivo human bladder tissue samples were topically treated with nanoparticles.
- Nanoparticles targeted specific bladder tumor proteins (CD47, Carbonic Anhydrase 9) or utilized tissue permeability.
- Multiplexed molecular imaging and receiver operating characteristic analysis (ROC AUC) were employed.
Main Results:
- The system achieved a high diagnostic accuracy with an ROC AUC of 0.93 for multiplexed imaging.
- Passively targeted nanoparticles also demonstrated excellent classification performance (ROC AUC of 0.93).
- Passive targeting resulted in 5-fold deeper penetration and 3.3-fold higher tumor binding compared to normal tissue.
Conclusions:
- The nanoparticle system shows significant promise for improving bladder cancer detection and resection.
- Passive nanoparticle targeting leverages an enhanced surface permeability and retention effect in bladder tumors.
- This technology could overcome limitations of current cystoscopy for nonmuscle invasive bladder cancer.
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