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

rylanda光纤微针装置（FMD）已经被发明出来，它可以显著增强光在组织中的穿透性，从而实现一种结合光和纳米药物输送的微创和更具选择性的光热治疗新体制。该装置由一根或多根光学透明玻璃纤维（直径约40微米）组成，通过一种新颖的支撑箍将其引导到患者的组织中。对于皮肤病学的应用，该装置可以贴在病人的皮肤上，机械压缩使纤维针滑过套圈，无痛地穿透皮肤，类似于蚊子叮咬的动力学。纤维尖端可放置在组织内理想的目标位置（可能深2mm）。一些纤维可能是中空的，可以将药物（化疗药物、纳米材料等）输送到特定的组织区域进行靶向治疗。随后将激光能量应用到固体纤维中，将有效地传输到含有光吸收纳米材料的目标组织，从而诱导选择性光热或光化学损伤。为了实现该装置用于癌症治疗的临床翻译，必须对其光学，机械和治疗能力有基本的了解。为了展示该技术的潜力，研究小组将研究目标组织为以下三个目标：1)机械穿透：设计和制造一个光纤微针装置（FMD），并利用白光摄影成像和称重传感器测试评估其在穿透离体猪皮肤中的性能。设计和制造单独的光纤微针，实心芯用于输送光，空心芯用于输送含有纳米颗粒的流体，并使用明场和荧光成像评估其光/流体输送性能。利用热成像和细胞活力测定评估口蹄疫光递送单独或与纳米颗粒联合的光热损伤特异性。所有目标都将涉及使用细胞组织代表模型和离体猪皮进行实验。每个目标都有相关的里程碑，要在这个项目的三年里完成。这项工作的完成将为使用FMD进行癌症治疗的动物和最终的人体临床试验提供必要的初步结果。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，极大地推进fmd介导的激光癌症治疗的发展。使用FMD，纳米粒子和光可以通过微创光纤微针传递到上皮表面以下几毫米的特定目标部位。由于目标组织中的纳米粒子对光辐射的选择性吸收，光学剂量可以更精确地传递，减少不必要的附带组织损伤和相关疼痛，并促进伤口更快愈合。该项目涉及组织力学（针刺）、组织光学（光输运）、纳米材料输运、热产生和输运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是改善癌症患者的生活质量。FMD是一种微创检测和治疗早期、位于组织表面下几毫米的小上皮癌的技术，如黑色素瘤、子宫癌和食管癌。早期发现和治疗癌症是提高生存率和降低发病率的关键。该FMD装置适合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。这个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元文化学术机会计划（MAOP）和弗吉尼亚理工大学工程多样性增强中心（CEED）等项目来增加工程领域的女性和少数族裔学生数量。该提案的资金将允许招募更多的女性和少数族裔学生到他的生物传输和光学实验室学习。

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.