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

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.

Interactions Between Tumor Biology and Targeted Nanoplatforms for Imaging Applications

“…Davis et al synthesized gold‐silica NPs as surface‐enhanced Raman scattering (SERS) capable NPs, that were targeted with Abs s420‐anti‐CA9, s440‐anti‐CD47, and s421‐anti‐IgG4 for active and passive targeting ( Figure ). The main results of this study were i) evidence of passive targeting of intra‐vesical NPs; ii) the EPR effect operated for topically applied NPs; and iii) the bladder tissue could be classified as normal or cancerous using multiplexed molecular SERS imaging 202. More examples of targeted imaging systems for detection of bladder cancer are summarized in Table 4.…”

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

“…[173] SERS/SERRS nanoprobes usually have three major parts: a metal core, a Raman reporter layer, and a shell (Figure 7a). [46] Kircher's team developed an SERRS-nanostar consisting of a gold core (75 nm), which was coated with a Raman reported dye (IR780 perchlorate) and silica with the conjugation of polyethylene glycol (PEG). [169] The shell provides the nanoprobes with biocompatibility and stability and allows them to conjugate with targeting and/or affinity molecules on the surface (Figure 7c).…”

“…[169] The shell provides the nanoprobes with biocompatibility and stability and allows them to conjugate with targeting and/or affinity molecules on the surface (Figure 7c). [187] Gambhir's group fabricated CA9-and CD47-targeted SERS NPs (s420-CA9 and s440-CD47, Figure 7c); [46] they proposed a promising application scheme that combines SERS imaging Adv. [169,176] Moreover, the shell can be radiolabeled for multimodal imaging (Figure 7e,f).…”

Fluorinated Polymer Mediated Transmucosal Peptide Delivery for Intravesical Instillation Therapy of Bladder Cancer

“…Bladder cancer (BCa) is the primary cause of cancer‐directed pathosis and mortality in urological cancerous diseases and has the highest life‐long follow‐up care and frequent treatment costs of all tumor patients . In the treatment of BCa, surgical intervention combined with intravesical instillation therapy has been the current standard treatment principle . The instillation of chemotherapeutics and/or immunomodulators after transurethral resection is designed to eliminate the remnant cancer cells and avert severe side effects of systemic drug administration .…”