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

基于超声的诊断和监测纳米颗粒释放药物治疗膀胱癌

• 批准号: 9618473
• 负责人: Joe Assouline
• 金额: $ 29.52万
• 依托单位: NANOMEDTRIX, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-07 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9618473
• 关键词: Advanced Malignant Neoplasm; Adverse effects; Anatomy; Antimitotic Agents; Antineoplastic Agents; Artificial nanoparticles; Binding; Biocompatible Materials; Biomedical Engineering; Bladder; Bladder Neoplasm; Bladder Tissue; Carcinoma; Chemicals; Clinic; Clinical; Clinical Trials; Collaborations; Contrast Media; Cultured Tumor Cells; Custom; Cystoscopy; Data; Development; Diagnostic; Documentation; Drug Delivery Systems; Early Diagnosis; Early treatment; Effectiveness; Ensure; Environment; Epirubicin; Exposure to; Faculty; Fluorescent Dyes; Functional Imaging; Gases; Goals; Image; Imaging Techniques; In Vitro; Injections; Intervention; Intravesical Administration; Iowa; Laboratories; Lead; Lesion; MRI Scans; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measurement; Methodology; Methods; Mind; Modality; Modeling; Molecular Weight; Monitor; Monoclonal Antibodies; Mus; Nanotechnology; Nucleosome Core Particle; Outcome; Patient-Focused Outcomes; Patients; Peptides; Pharmaceutical Preparations; Phase; Research; Research Personnel; Resolution; Schedule; Series; Silicon Dioxide; Small Business Innovation Research Grant; Smooth Muscle; Specificity; Speed; Techniques; Technology; Testing; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Time; Transitional Cell Carcinoma; Translating; Transurethral Resection; Treatment Protocols; Tumor Markers; Ultrasonography; United States; Universities; Urology; accurate diagnosis; advanced system; antitumor agent; antitumor drug; base; bladder transitional cell carcinoma; cancer cell; cancer therapy; chemotherapy; clinical application; commercialization; common treatment; contrast enhanced; cost; cost effective; drug synthesis; experimental study; image processing; imaging modality; imaging system; improved; improved outcome; in vivo; in vivo evaluation; intravesical; minimally invasive; molecular imaging; mouse model; nano; nanomaterials; nanoparticle; neoplastic cell; non-invasive monitor; novel; novel strategies; particle; phase 2 study; preclinical study; prognostic; prototype; radiologist; scale up; screening; soft tissue; sound; submicron; success; targeted delivery; tool; tumor; tumor growth

Project Summary/Abstract Transitional cell carcinoma (TCC) of the bladder is the fifth most common form of cancer in the United States, with over 79,000 new cases expected for 2017. For early stage carcinomas, the most common treatment regimen is to initially perform transurethral resection of bladder tumor (TURBT) using an invasive cystoscopic approach with non-specific fluorescent dyes to highlight the lesions. Even then, small lesions are often missed leading to the cancer recurring in up to 70% of patients and further progresses to advanced cancer in up to 20% of patients following TURBT. Compared to cystoscopy, high resolution ultrasound (HRUS) is low-cost, minimally invasive, and provides an in-depth view of the smooth muscle layer and surrounding tissues of the bladder with spatial resolution as low as 30 m. Despite advances in HRUS, current imaging systems are limited to anatomical data, as it can neither provide functional or molecular imaging data, nor facilitate any interventional approach, alone. The implementation of a targeted contrast enhancement is necessary to elevate the data acquired from even the most advanced system. Clinically approved ultrasound contrast agents operate on the principle that the speed of sound is drastically different high molecular weight gases than in soft tissue. While highly echogenic, these agents are too large and too short-lived to be useful for functional imaging. To improve upon this approach, sub-micron ultrasound agents are being used experimentally, though the resulting agents are limited and have not been applied to TCC. Clinical applications resulting from this approach will benefit by 1) improvement of current screening methods (expedited, cheaper and dynamic), and 2) facilitation of specific delivery of intravesical treatment, specifically with non-invasive monitoring. We propose a material based on mesoporous silica nanoparticles (MSN), functionalized for diagnostic HRUS as well as interventional imaging following delivery of a therapeutic agent. We propose a rigorous in vitro / in vivo testing methodology to characterize the MSN and optimize its diagnostic and therapeutic capabilities. Upon completion the MSN would fulfill a desperately needed alternative to the current invasive and TCC treatment. If successful, the end product represents a highly marketable cost effective material that can be deployed clinically, ultimately improving patient outcomes. Our team of biomedical engineers, radiologists, urology researchers and clinicians are uniquely poised to carry out this research. The use of biocompatible materials and a short peptide for targeting, as opposed to many pre-clinical studies which involve monoclonal antibodies, ensures that the proposed material is of immediate clinical and commercial relevance. This proposal paves the way for SBIR Phase II studies, in which long-term survival and the scale-up of synthesis for commercial purposes will be evaluated.

项目摘要/摘要 膀胱的过渡细胞癌（TCC）是美国第五大最常见的癌症形式， 预计2017年预计有79,000例新病例。对于早期癌，最常见的治疗方法 方案最初使用侵入性膀胱镜进行膀胱肿瘤（TURBT）进行静脉尿素切除术 与非特异性荧光染料接近以突出病变。即使那时，小病变也经常会错过 导致多达70％的患者反复出现癌症，并进一步发展为晚期癌症，多达20％ turbt之后的患者。与膀胱镜检查相比，高分辨率超声（HRUS）是低成本，最少的 侵入性，并提供了平滑肌层和周围组织的深度视图 空间分辨率低至30℃。尽管HRUS取得了进步，但当前的成像系统仅限于 解剖学数据可以提供功能或分子成像数据，也可以促进任何介入 方法，一个人。必须实现目标对比增强以提高数据 从最先进的系统中获得。 临床批准的超声对比剂的运作原则是声音速度很大 在软组织中，不同的高分子量气体不同。虽然高度回声，但这些试剂太大了， 太短暂了，无法对功能成像有用。为了改善这种方法，亚微米超声剂 尽管产生的代理受到限制，并且尚未应用于TCC，但正在实验中使用。 通过这种方法产生的临床应用将受益1）改进当前筛查方法 （加快，便宜且动态），以及2）促进特定的静脉治疗的特定递送 进行非侵入性监测。我们提出了一种基于介孔二氧化硅纳米颗粒（MSN）的材料， 在交付治疗剂后，功能化用于诊断HRUS以及介入的成像。 我们提出了一种严格的体外 /体内测试方法，以表征MSN并优化其诊断 和治疗能力。完成后，MSN将实现迫切需要的替代方案 当前的侵入性和TCC治疗。如果成功，最终产品代表了高度销售的成本效益 可以在临床上部署的材料，最终改善患者的结果。 我们的生物医学工程师，放射科医生，泌尿外科研究人员和临床医生团队被毒死 这项研究。使用生物相容性材料和短肽来靶向，而不是许多 涉及单克隆抗体的临床前研究确保提出的材料是立即的 临床和商业意义。该建议为SBIR II期研究铺平了道路，其中长期 将评估生存期和用于商业目的的合成规模。