Fiberoptic Microneedle Device for Nanoparticle-Enhanced Photothermal Therapy of A

描述（由申请人提供）：本提案的目标是通过使用我们的光纤微针器械（FMD）开发一种针对浸润性膀胱癌的变革性选择性治疗。具体来说，我们假设“FMD将通过纳米颗粒增强光热疗法实现2-3期浸润性膀胱癌的首次微创治疗。“FMD将用于选择性地提供称为单壁纳米角（SWNHs）的新型光吸收颗粒，并与激光能量结合，以治疗嵌入膀胱肌肉和浆膜层的靶向肿瘤。FMD将有能力将这些发色团直接注射到肿瘤部位，并提供准确的激光激发，以最大限度地提高肿瘤死亡率，并最大限度地减少全身毒性。研究将集中在针力学，流体/颗粒分散和光传输的分析和建模。为了实现该技术的治愈潜力，将根据以下目标进行研究：（1）证明FMD靶向渗透到选定膀胱深度的能力以及在来自正常大鼠、狗和猪的切除膀胱中的纳米颗粒和光热递送的能力;（2）在临床膀胱镜内整合FMD的多功能光学和纳米颗粒递送能力，并使用切除的膀胱评估治疗;（3）评价FMD在啮齿动物和犬移行细胞癌模型中进行有效纳米颗粒增强光热治疗的能力。目标1的完成将允许对FMD用于机械插入和光学/纳米颗粒递送的多功能能力进行关键表征，所述机械插入和光学/纳米颗粒递送是开发和利用用于治疗浸润性膀胱癌所必需的。目标2的结果将产生与临床膀胱镜集成的新型仪器（FMD）。目的3的结论将为我们的假设提供明确的答案，即FMD可以在大鼠和狗模型中首次微创治疗2-3期浸润性膀胱癌。 公共卫生相关性：目前治疗浸润性膀胱癌的方法是手术切除膀胱并丧失排尿和性功能。这项研究为证明使用新型仪器治疗侵袭性浸润性膀胱癌以保留组织功能的可行性迈出了积极的一步。

DESCRIPTION (provided by applicant): The goal of this proposal is to develop a transformative, selective treatment for invasive bladder cancer through the use of our fiberoptic microneedle device (FMD). Specifically, we hypothesize that "the FMD will enable the first minimally invasive treatment of stage 2-3 invasive bladder cancer through nanoparticle-enhanced photothermal therapy." The FMD will be used to selectively deliver novel photoabsorbing particles known as single walled nanohorns (SWNHs) in conjunction with laser energy to treat targeted tumors embedded within muscular and serosal layers of the bladder. The FMD will have the ability to both inject these chromophores directly into the tumor site and deliver accurate laser excitation to maximize tumor death and minimize systemic toxicity. Research will focused on analysis and modeling of the needle mechanics, fluid/particle dispersal, and light delivery. To realize the healing potential of this technology, the study will be conducted according to the following objectives: (1) Demonstrate the capability of the FMD for targeted penetration into selected bladder depths and nanoparticle and photothermal delivery in excised urinary bladders from normal rats, dogs, and pigs; (2) Integrate multifunctional optical and nanoparticle delivery capabilities of FMD within a clinical cystoscope and evaluate treatment using excised urinary bladders; (3) Evaluate the capability of the FMD for effective nanoparticle-enhanced photothermal therapy in rodent and canine models of transitional cell carcinoma. Completion of Objective 1 will allow critical characterization of the multifunctional capability of the FMD for mechanical insertion and optical/nanoparticle delivery necessary for development and utilization for the treatment of invasive bladder cancer. The result of Objective 2 will yield a novel instrument (FMD) which is integrated with a clinical cystoscope. Conclusion of Objective 3 will provide definitive answer to our hypothesis that the FMD can enable the first minimally invasive treatment of stage 2-3 invasive bladder cancer in rat and dog models. PUBLIC HEALTH RELEVANCE: The current method of treating invasive bladder cancer is surgical resection of the bladder and loss of urinary and sexual function. This research provides a positive step toward demonstrating the feasibility of treating aggressive invasive bladder cancer using a novel instrument in order to spare tissue function.