Surface-Enhanced Raman Scattering Nanoparticles for Multiplexed Imaging of Bladder Cancer Tissue Permeability and Molecular Phenotype

ACS Nano. 2018 Oct 23;12(10):9669-9679. doi: 10.1021/acsnano.8b03217. Epub 2018 Sep 11.


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.

Keywords: Raman endoscopy; bladder cancer; molecular imaging; multiplexing; passive targeting; surface-enhanced Raman scattering.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Neoplasm / analysis*
  • Antigens, Neoplasm / metabolism
  • CD47 Antigen / analysis*
  • CD47 Antigen / metabolism
  • Carbonic Anhydrase IX / analysis*
  • Carbonic Anhydrase IX / metabolism
  • Cell Line, Tumor
  • HCT116 Cells
  • Humans
  • Molecular Imaging*
  • Nanoparticles / chemistry*
  • Particle Size
  • Permeability
  • Phenotype
  • Spectrum Analysis, Raman
  • Surface Properties
  • Urinary Bladder Neoplasms / diagnostic imaging*
  • Urinary Bladder Neoplasms / metabolism


  • Antigens, Neoplasm
  • CD47 Antigen
  • CD47 protein, human
  • CA9 protein, human
  • Carbonic Anhydrase IX