nn8b03217_si_001.pdf (1.28 MB)
Surface-Enhanced Raman Scattering Nanoparticles for Multiplexed Imaging of Bladder Cancer Tissue Permeability and Molecular Phenotype
journal contribution
posted on 2018-09-11, 00:00 authored by Ryan M. Davis, Bernhard Kiss, Dharati R. Trivedi, Thomas J. Metzner, Joseph C. Liao, Sanjiv S. GambhirBladder 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.