Ultrasound-based diagnostic and monitoring of bladder cancer treatment with drug released from nanoparticles

Project Summary Abstract Transitional cell carcinomaTCCof the bladder is the fifth most common form of cancer in the United Stateswith overnew cases expected forFor early stage carcinomasthe most common treatment regimen is to initially perform transurethral resection of bladder tumorTURBTusing an invasive cystoscopic approach with non specific fluorescent dyes to highlight the lesionsEven thensmall lesions are often missed leading to the cancer recurring in up toof patients and further progresses to advanced cancer in up toof patients following TURBTCompared to cystoscopyhigh resolution ultrasoundHRUSis low costminimally invasiveand provides an in depth view of the smooth muscle layer and surrounding tissues of the bladder with spatial resolution as low asmDespite advances in HRUScurrent imaging systems are limited to anatomical dataas it can neither provide functional or molecular imaging datanor facilitate any interventional approachaloneThe implementation of a targeted contrast enhancement is necessary to elevate the data acquired from even the most advanced systemClinically approved ultrasound contrast agents operate on the principle that the speed of sound is drastically different high molecular weight gases than in soft tissueWhile highly echogenicthese agents are too large and too short lived to be useful for functional imagingTo improve upon this approachsub micron ultrasound agents are being used experimentallythough the resulting agents are limited and have not been applied to TCCClinical applications resulting from this approach will benefit byimprovement of current screening methodsexpeditedcheaper and dynamicandfacilitation of specific delivery of intravesical treatmentspecifically with non invasive monitoringWe propose a material based on mesoporous silica nanoparticlesMSNfunctionalized for diagnostic HRUS as well as interventional imaging following delivery of a therapeutic agentWe propose a rigorous in vitroin vivo testing methodology to characterize the MSN and optimize its diagnostic and therapeutic capabilitiesUpon completion the MSN would fulfill a desperately needed alternative to the current invasive and TCC treatmentIf successfulthe end product represents a highly marketable cost effective material that can be deployed clinicallyultimately improving patient outcomesOur team of biomedical engineersradiologistsurology researchers and clinicians are uniquely poised to carry out this researchThe use of biocompatible materials and a short peptide for targetingas opposed to many pre clinical studies which involve monoclonal antibodiesensures that the proposed material is of immediate clinical and commercial relevanceThis proposal paves the way for SBIR Phase II studiesin which long term survival and the scale up of synthesis for commercial purposes will be evaluated Project Narrative In bladder cancerscreening constraints lead to missed lesions resulting in grave consequencesThe harsh environment of the bladder hinders effectiveness of anti tumor drugsallowing cancer to recur in up toof patients and proceed to advanced stage in up toof patientsIn this projectwe will evaluate a nanomaterial contrast agent with dual purposeto specifically bind cancer cells for accurate diagnosis through functionalization making it visible with ultrasoundandto carry a therapeutic payload of epirubicin or other known anti tumor agentswhile simultaneously protecting the healthy bladder from their tumoricidal effectsThis novel approach will ultimately lead to improved outcomes and provide evidence for the clinical and commercial potential benefits of our platform nanotechnology