Fiberoptic Microneedle Device for Combined Light and Nanomedicine Delivery: Mimicking Nature's Design of a Mosquito

用于组合光和纳米药物输送的光纤微针装置：模仿蚊子的自然设计

• 批准号: 0933571
• 负责人: Christopher Rylander
• 金额: $ 30万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0933571&HistoricalAwards=false
• 关键词: Fiberoptic; Microneedle; Device; Combined; Light

0933571RylanderA fiberoptic microneedle device, FMD, has been invented that can significantly enhance light penetration in tissue to enable a new regime of minimally-invasive and more selective photothermal therapy combining light and nanomedicine delivery. The device is comprised of one or more optically transparent glass fibers (~40 microns in diameter) which are guided into a patient's tissue by a novel support ferrule. For dermatological applications, the device may be placed against a patient's skin, and mechanical compression causes the fiber needles to slide through the ferrule and painlessly penetrate the skin, similar to the dynamics of a mosquito bite. The fiber tips may be positioned at desirable target positions (potentially 2mm deep) within tissue. Some fibers may be hollow, enabling delivery of drugs (chemotherapeutic agents, nanomaterials etc.) to specific tissue regions for targeted treatment. Subsequent application of laser energy into the solid fibers will be transmitted efficiently to the target tissue containing the light-absorbing nanomaterials, thereby inducing selective photothermal or photochemical damage. To achieve clinical translation of this device for cancer treatment a fundamental understanding of its optical, mechanical, and therapeutic capability must be performed. To demonstrate the potential of this technology the research team has organized the research goals in the following three objectives:1) Mechanical Penetration: Design and fabricate a fiberoptic microneedle device (FMD) and evaluate its performance in penetrating ex vivo porcine skin using white light photographic imaging and load-cell testing2) Optical/Fluid Delivery: Design and fabricate individual fiberoptic microneedles with solid cores to deliver light and hollow cores to deliver fluids containing nanoparticles, and evaluate their light/fluid delivery performance using brightfield and fluorescence imaging3) Thermal/Therapeutic: Evaluate photothermal damage specificity of FMD light delivery alone or in combination with nanoparticles using thermal imaging and cell viability assaysAll objectives will involve experimentation using cell-based tissue representative phantoms and ex vivo porcine skin. Each objective has associated milestones to be completed during each of the three years of this project. Completion of this work will provide preliminary results necessary to move forward with animal and eventually human clinical trials for cancer treatment using the FMD. The proposed research will greatly advance development of FMD-mediated laser cancer therapies by providing an understanding of the optical, mechanical, and therapeutic capabilities of this technology. Using the FMD, nanoparticles and light may be delivered to specific target sites several millimeters beneath an epithelial surface via minimally-invasive fiberoptic microneedles. Due to selective absorption of optical radiation by the nanoparticles in the target tissue, the optical dose can be more precisely delivered, reducing unwanted collateral tissue damage and associated pain, and promoting faster wound healing. This project involves interdisciplinary experimentation and modeling of tissue mechanics (needle penetration), tissue optics (light transport), transport of nanomaterials, heat generation and transport, and cellular injury. Long-range societal impact of this work will be improved quality of life for cancer patients. The FMD is an enabling technology for minimally-invasive detection and treatment of early stage, small epithelial cancers located a few millimeters under the tissue surface, such as melanoma, uterine, and esophageal cancer. Early stage detection and treatment of cancer is the key to enhanced survival and diminished morbidity. The FMD device is appropriately scaled for minimally invasive selective detection and treatment of early stage tumors. Furthermore, the FMD is well suited to deliver photosensitizing drugs or nanomaterials to increase the selective tumor destruction while maintaining the viability of the surrounding healthy tissue. The interdisciplinary nature of this project will provide opportunities for students from different scientific fields to gain experience in experimental design, engineering, imaging, and computational modeling. The PI is devoted to increasing the number of females and minorities within the engineering field through active participation in programs such as Multicultural Academic Opportunities Program (MAOP), and Center for the Enhancement of Engineering Diversity (CEED) at Virginia Tech. Funding from this proposal will allow recruitment of additional female and minority students to study in his biotransport and optics laboratory.

已经发明了一种光纤微针装置FMD，其可以显著增强光在组织中的穿透，以实现结合光和纳米医学递送的微创且更具选择性的光热治疗的新方案。 该器械由一根或多根光学透明玻璃纤维（直径约40微米）组成，通过新型支撑套圈引导进入患者组织。 对于皮肤病学应用，该装置可以抵靠患者的皮肤放置，并且机械压缩导致光纤针滑动通过套圈并且无痛地穿透皮肤，类似于蚊子叮咬的动力学。光纤尖端可以定位在组织内的期望目标位置（可能2 mm深）处。一些纤维可以是中空的，使得能够递送药物（化疗剂、纳米材料等）。用于靶向治疗的特定组织区域。 随后将激光能量施加到固体纤维中将有效地传输到含有光吸收纳米材料的靶组织，从而诱导选择性光热或光化学损伤。 为了实现该设备用于癌症治疗的临床转化，必须对其光学、机械和治疗能力进行基本了解。为了证明该技术的潜力，研究团队将研究目标分为以下三个目标：1）机械穿透：设计和制造光纤微针装置（FMD），并使用白色光摄影成像和测压元件测试评价其穿透离体猪皮肤的性能2）光学/流体输送：设计和制造具有实心芯以递送光和空心芯以递送含有纳米颗粒的流体的单个光纤微针，并使用明场和荧光成像评估它们的光/流体输送性能。3）热/治疗：使用热成像和细胞活力测定评估单独或与纳米颗粒组合的FMD光递送的光热损伤特异性所有目标将涉及使用基于细胞的组织代表性体模和离体猪皮进行实验。每个目标都有相关的里程碑，在本项目的三年中的每一年都要完成。这项工作的完成将提供必要的初步结果，以推进动物和最终人类临床试验，使用口蹄疫治疗癌症。 拟议的研究将通过提供对该技术的光学、机械和治疗能力的理解，大大推进FMD介导的激光癌症治疗的发展。使用FMD，纳米颗粒和光可以通过微创光纤微针递送到上皮表面下方几毫米的特定靶位点。 由于靶组织中的纳米颗粒选择性吸收光辐射，可以更精确地递送光学剂量，减少不必要的附带组织损伤和相关疼痛，并促进更快的伤口愈合。 该项目涉及组织力学（针穿透），组织光学（光传输），纳米材料的运输，热生成和运输以及细胞损伤的跨学科实验和建模。 这项工作的长期社会影响将改善癌症患者的生活质量。FMD是一种用于微创检测和治疗位于组织表面下几毫米处的早期小上皮癌（如黑色素瘤、子宫癌和食管癌）的技术。 癌症的早期发现和治疗是提高生存率和降低发病率的关键。 FMD设备被适当地缩放以用于早期肿瘤的微创选择性检测和治疗。此外，FMD非常适合递送光敏药物或纳米材料以增加选择性肿瘤破坏，同时保持周围健康组织的活力。该项目的跨学科性质将为来自不同科学领域的学生提供机会，以获得实验设计，工程，成像和计算建模方面的经验。 PI致力于通过积极参与多文化学术机会计划（MAOP）和弗吉尼亚理工大学工程多样性增强中心（CEED）等计划，增加工程领域的女性和少数民族人数。 该提案的资金将允许招募更多的女性和少数民族学生在他的生物运输和光学实验室学习。