Bioresorbable Nanoparticles for Visual Detection of Early-Stage Dental Caries

项目摘要/摘要 该项目响应了NIDCR确定的开发改进的检测和预测方法的需求 促进龋齿(龋齿)的进展，以改善人类健康。在世界范围内，龋齿是最常见的 影响到几乎每个人的慢性病。牙病是造成经济和社会损失的主要原因 会导致并发症，包括疼痛、牙齿脱落甚至死亡。一般来说，不活跃的皮损不需要治疗。 而活动性病变则是如此。早期活动性皮损允许保守治疗，而空洞皮损则需要保守治疗。 更昂贵和更具侵入性的修复。自40年代初S以来，龋病的诊断一直是目视和 使用探牙器，但会漏掉早期的龋齿，并且探牙器可能会导致空洞。或者，X- 射线能识别更充分的空洞，但不能识别早期形成的病变。更新的方法 龋病诊断效益不大，给牙医和患者带来了更大的成本。目前的方法诊断为 牙釉质表面的缺陷，但不能区分“活性”，这是现代牙科的一项关键需求。我们的目标是 开发一种新的临床有效的测试，以诊断早期和活动的龋齿损害，也使有效的 监测保守治疗。我们发明了一种纳米颗粒技术，专门针对 活动性龋损。这些纳米颗粒是由食品级玉米淀粉制成的，并已被功能化 专门针对龋齿病变的皮下组织。它们被标记了一种安全的荧光染料，所以龋齿 将使用标准的牙科固化灯照明并很容易被看到，使牙医能够快速区分 龋齿病变是活跃的还是不活跃的，并监测治疗结果。本品为漱口水或 口腔凝胶在水中含有低浓度的纳米颗粒，使人能够目测到早期的活动 牙齿表面原本看不见的龋齿病变，因为极小的纳米颗粒可以穿透 通过体表微通道进入早期活跃的亚表面病变。以淀粉为基础的性质 纳米颗粒有助于人类唾液中存在的淀粉酶的快速降解，因此牙齿不再 在离开牙医办公室时做荧光检查。更早地发现龋齿和以前的疾病治疗 发生空化时，将防止侵入性治疗，从而实现微创 牙科和改善口腔健康。我们的第一阶段研究已经证明了这项技术的潜力， 并成功地对纳米颗粒的官能团进行了优化，为可行的产品提供了足够的 靶向和荧光对比度可供牙科专业人员在不同牙齿上宏观查看 当使用牙科诊所提供的标准牙科固化灯时，可在表面上使用该灯。第二阶段涉及体外培养 评估该试验的诊断能力，包括体外敏感性和特异性、体内生物相容性 以及FDA提交、临床可行性和生产规模所需的研究。成功完成 第二阶段的AIMS将促进第三阶段的商业化，并满足临床开发、监管和 制造里程碑以支持临床验证和纵向临床结果研究。

PROJECT SUMMARY/ABSTRACT This project responds to the need identified by NIDCR to develop improved methods to detect and predict progression of dental caries (tooth decay) to improve human health. Worldwide, caries is the most common chronic disease affecting almost everyone. Dental disease is a major cause of economic and social loss and leads to complications including pain, tooth loss and even death. Generally inactive lesions require no treatment while active lesions do. Early active lesions permit conservative treatment, whereas cavitated lesions require more costly and invasive restoration. Since the early 40’s, caries diagnosis has been performed visually and using a dental explorer, but early cavities are missed and the explorer can cause cavitation. Alternatively, X- Rays identify more fully developed cavities but are unable to identify early forming lesions. Newer methods for caries diagnosis show little benefit and incur greater cost to dentist and patient. Current methods diagnose a surface defect in the enamel but cannot distinguish “activity”, a critical need in modern dentistry. Our goal is to develop a new clinically valid test to diagnose early and active carious lesions that also enables effective monitoring of conservative treatment. We have invented a nanoparticle technology which specifically targets active carious lesions. The nanoparticles are made from food grade corn starch and have been functionalized to specifically target the subsurface of carious lesions. They are tagged with a safe fluorescent dye so the caries will illuminate and be easily seen using a standard dental curing lamp, allowing dentists to quickly differentiate whether a carious lesion is active or inactive and to monitor treatment results. The product is a mouth rinse or oral gel containing a low concentration of the nanoparticles in water, enabling visual detection of early active carious lesions otherwise invisible on the tooth surface, because the extremely small nanoparticles can penetrate through surface microchannels into the early active sub-surface lesion. The starch-based nature of the nanoparticles facilitates rapid degradation by amylase enzyme present in human saliva, so teeth will no longer fluoresce upon leaving the dentist’s office. With earlier detection of caries and treatment of the disease before cavitation occurs, invasive treatments will be prevented, resulting in the enablement of Minimally Invasive Dentistry and improved oral health. Our Phase I research has demonstrated the potential of this technology, and the functionalities on the nanoparticles were successfully optimized to provide a viable product with sufficient targeting and fluorescence contrast to be macroscopically visible by the dental professional on various tooth surfaces when using a standard dental curing light available in a dental practice. Phase II involves in vitro assessment of the test’s diagnostic capabilities including in vitro sensitivity and specificity, in vivo biocompatibility and studies required for FDA submission, clinical feasibility, and scaling of production. Successful completion of the Phase II Aims will facilitate commercialization in Phase III, and meet clinical development, regulatory and manufacturing milestones to support clinical validation and longitudinal clinical outcome studies.