Bioresorbable Nanoparticles for Visual Detection of Early-Stage Dental Caries

用于早期龋齿视觉检测的生物可吸收纳米颗粒

• 批准号: 10018844
• 负责人: Steven Bloembergen
• 金额: $ 70.56万
• 依托单位: GREENMARK BIOMEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10018844
• 关键词: Address; Adopted; Affect; Amylases; Blinded; Carbohydrates; Cessation of life; Characteristics; Charge; Chronic Disease; Clinical; Clinical assessments; Cyclic GMP; Data; Defect; Dental; Dental Enamel; Dental General Practice; Dental Implants; Dental caries; Dentistry; Dentists; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Early Diagnosis; Economics; Ensure; Enzymes; Evaluation; FDA approved; Failure; Feedback; Fluorescence; Fluorescent Dyes; Food; Formulation; Gel; Goals; Health; Healthcare; Hour; Human; Image; In Vitro; Infection; Legal patent; Lesion; Light; Methods; Mission; Modernization; Monitor; National Institute of Dental and Craniofacial Research; Nature; Operative Surgical Procedures; Oral; Oral cavity; Oral health; Outcome; Outcome Study; Pain; Particle Size; Patient-Focused Outcomes; Patients; Penetration; Performance; Phase; Preclinical Testing; Process; Production; Quality of life; Reproducibility; Research; Risk Assessment; Roentgen Rays; Safety; Saliva; Sensitivity and Specificity; Small Business Innovation Research Grant; Starch; Surface; Tactile; Technology; Testing; Tooth Diseases; Tooth Loss; Tooth structure; Toxicology; Transillumination; United States National Institutes of Health; Validation; Visual; Water; aqueous; base; biomaterial compatibility; clinical development; commercialization; cost; cost estimate; demineralization; design; improved; in vivo; micropore; minimally invasive; nanoparticle; novel diagnostics; overtreatment; particle; patient population; point of care; pre-clinical; prevent; programs; prototype; public health relevance; remineralization; restoration; restorative treatment; social; success; tooth surface; usability; validation studies

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.

项目概要/摘要 该项目响应了 NIDCR 确定的开发改进方法来检测和预测的需求 龋齿（蛀牙）的进展以改善人类健康 在世界范围内，龋齿是最常见的。 慢性疾病几乎影响每个人，是造成经济和社会损失的主要原因。 导致并发症，包括疼痛、牙齿脱落甚至死亡，通常不活动的病变不需要治疗。 早期活动性病变允许保守治疗，而空洞性病变则需要保守治疗。 自 20 世纪 40 年代初以来，龋齿诊断一直通过目视和侵入性修复来进行。 使用牙科探查器，但会错过早期蛀牙，并且探查器可能会导致空化。 射线可以识别更完全发育的空洞，但无法识别早期形成的病变。 目前的方法诊断龋齿几乎没有什么好处，而且会给牙医和患者带来更大的成本。 牙釉质表面缺陷但无法区分“活动”，这是现代牙科的一个关键需求。 开发一种新的临床有效测试来诊断早期和活动性龋损，也能够有效 我们发明了一种专门针对保守治疗的纳米颗粒技术。 活性龋齿病变纳米颗粒由食品级玉米淀粉制成，并已被功能化。 专门针对龋齿的表面下，它们用安全的荧光染料标记，因此可以消除龋齿。 使用标准牙科固化灯会发光并容易看到，使牙医能够快速区分 龋齿是否活跃或不活跃，并监测治疗结果 该产品是漱口水或漱口水。 口腔凝胶中含有低浓度的纳米粒子，能够目视检测早期活性物质 龋齿病变在牙齿表面是看不见的，因为极小的纳米粒子可以穿透 通过表面微通道进入早期活动的亚表面病变。 纳米粒子促进人类唾液中存在的淀粉酶快速降解酶，因此牙齿不再 离开牙医诊所时会发出荧光，以便尽早发现龋齿并提前治疗疾病。 发生空化，将阻止侵入性治疗，从而实现微创治疗 牙科和改善口腔健康我们的第一阶段研究证明了这项技术的潜力， 并且纳米颗粒的功能被成功优化，以提供具有足够性能的可行产品 牙科专业人员可以在各种牙齿上宏观地看到目标和荧光对比度 使用牙科诊所中可用的标准牙科固化灯时的表面第二阶段涉及体外。 评估测试的诊断能力，包括体外敏感性和特异性、体内生物相容性 以及 FDA 提交、临床可行性和成功完成生产规模所需的研究。 第二阶段的目标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。

项目成果

Early occlusal caries detection using targeted fluorescent starch nanoparticles.

使用靶向荧光淀粉纳米颗粒进行早期咬合龋齿检测。

• DOI: 10.1016/j.jdent.2022.104243
• 发表时间: 2022
• 期刊: Journal of dentistry
• 影响因子: 4.4
• 作者: Jones,NathanA;Bloembergen,Wendy;Tenuta,LiviaMA;Flannagan,SusanE;Jones,GlennW;Pan,Li-Chi;Newton,Mariah;Clarkson,BrianH;Lahann,Joerg;Bloembergen,Steven;González-Cabezas,Carlos
• 通讯作者: González-Cabezas,Carlos