Peptide-mediated targeting mesoporous silica nanoparticles: A novel tool for fighting bladder cancer

Abstract

Transitional cell carcinoma of the bladder is particularly devastating due to its high rate of recurrence and difficulty in retention of treatments within the bladder. Current cystoscopic approaches to detect and stage the tumor are limited by the penetrative depth of the cystoscope light source, and intravesical dyes that highlight tumors for surgical resection are non-specific. To address the needs for improved specificity in tumor detection and follow-up, we report on a novel technology relying on the engineered core of mesoporous silica (MSN) with surface modifications that generate contrast in fluorescence and magnetic resonance imaging (MRI). The particle surface was further functionalized to include a bladder cancer cell specific peptide, Cyc6, identified via phage display. This peptide possesses nanomolar specificity for bladder cancer cells and homology across multiple species including mouse, canine, and human. Our study takes advantage of its target expression in bladder tumor which is not expressed in normal bladder wall. When functionalized to MSN, the Cyc6 improved binding efficiency and specificity for bladder cancer cells in vitro. In an in vivo model, MSN instilled into bladders of tumor-bearing mice enhanced T1-and T2-weighted MRI signals, improving the detection of the tumor boundaries. These findings support the notion that our targeted nanomaterial presents new options for early detection and eventual therapeutic intervention. Ultimately, the combination of real-time and repeated MRI evaluation of the tumors enhanced by nanoparticle contrast have the potential for translation into human clinical studies for tumor staging, therapeutic monitoring, and drug delivery.