Fiberoptic Microneedle Device for Nanoparticle-Enhanced Photothermal Therapy of A

描述(申请人提供)：这项提案的目标是通过使用我们的光纤微针设备(FMD)开发一种变革性的、选择性的浸润性膀胱癌治疗方法。具体地说，我们假设“FMD将通过纳米颗粒增强的光热疗法实现对2-3期浸润性膀胱癌的第一次微创治疗。”FMD将被用于选择性地输送被称为单壁纳米角(SWNH)的新型光吸收颗粒，并结合激光能量来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入肿瘤部位，并提供准确的激光激发，以最大限度地提高肿瘤死亡率，并将全身毒性降至最低。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上。为了实现这项技术的治愈潜力，本研究将根据以下目标进行：(1)展示FMD靶向穿透选定的膀胱深度和特定深度的能力，以及(3)显示FMD在切除的大鼠、狗和猪的膀胱内进行光热治疗的能力；(2)将FMD的多功能光学和纳米颗粒输送能力整合到临床膀胱镜中，并评估使用切除尿囊进行治疗的能力；(3)评估FMD在啮齿动物和犬的移行细胞癌模型中进行纳米颗粒强化光热治疗的能力。目标1的完成将使人们能够对FMD用于机械插入和光学/纳米颗粒输送的多功能能力进行关键表征，这是开发和利用其治疗浸润性膀胱癌所必需的。目标2的结果将产生一种与临床膀胱镜集成的新型仪器(FMD)。目标3的结论将为我们的假设提供明确的答案，即FMD可以实现对大鼠和狗模型2-3期浸润性膀胱癌的首次微创治疗。 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器械治疗侵袭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.