CAREER: Acousto-Bioelectronics

这个CAREER项目是全球努力征服癌症的一部分，癌症是第二大死亡原因。尽管在研究和开发方面投入了巨大的资金，但作为一种可行的癌症治疗方法，临床上的成功却很少。癌症治疗的最新进展导致植入式医疗设备（IMD）成为可行的药物，因为它们具有定位治疗的能力，尽管数量有限。然而，目前可用的IMD介导的癌症治疗通常局限于每次治疗的单次不可重复施用。这些局限性，沿着许多风险，如痛苦的手术、导管感染风险和器械故障，通常阻碍了IMD在癌症治疗中的使用。更重要的是，由于癌症的复杂性、多样性和异质性，单一的治疗方法无法有效地管理癌症。因此，该CAREER项目研究了一种多功能工程解决方案，其形式为声学驱动的可植入微系统，该系统提供了多模式癌症治疗的定制组合：氧气，化疗药物和光。结合起来，该项目旨在建立“声生物电子学”领域，为下一代IMD带来新的理论和理解。此外，该项目通过指导研究生和本科生，特别是代表性不足的少数民族和女性学生，开发跨学科课程，并创建从基础理论到实践活动的教学资源，将研究与教育场所相结合。虽然IMD正在改变现代医疗保健，但由于其寿命短，目前无法治愈癌症。这是复杂的事实，许多癌症可以复发或转移扩散。该CAREER项目的总体目标是利用工程和医疗保健领域的跨领域创新，创建一个超声驱动的植入式微系统，实现多模式癌症治疗的定制组合。本研究（1）阐明了Platonic固体结构的未开发潜力，用于IMD的高效全向超声供电方案，利用独特的3D可打印钛酸钡超声接收器。(2)通过超声提供足够的功率，微系统能够通过受控的电化学和光化学过程原位产生氧气、顺铂和光。因此，它被称为氧增强化学-光动力疗法。(3)该微系统可能实现临床证明的超加性抗癌效果-比任何单一疗法或理论组合都强。微系统介导的多模式癌症治疗将通过采用临床相关模型（体外和体内癌症模型）进行综合评价来验证。该项目的结果证明了IMD介导的多模式癌症治疗的发展是合理的，该治疗可能会帮助患有侵袭性和致命性癌症类型的患者，而这些患者的治疗选择有限。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This CAREER project is a part of a global effort to conquer cancer, the second leading cause of death. Despite the enormous investments in research and development, there have been scant clinical successes as a viable cancer therapy. Recent advancements in cancer therapy have resulted in the emergence of implanted medical devices (IMDs) into feasible medicines, owing to their capacity to localize treatments, albeit limited in numbers. However, currently available IMDs-mediated cancer treatments are often confined to a single, non-replenishable administration per therapy. These limitations, along with a number of risks such as painful surgery, infection risk in the catheter, and device failure, have generally hampered the usage of IMDs in cancer treatment. More importantly, cancer cannot be effectively managed with a single therapeutic approach due to its complex, diverse, and heterogeneous nature. As such, this CAREER project investigates a versatile engineering solution in the form of an acoustically driven implantable microsystem that provides a tailored combination of multimodal cancer therapeutics: oxygen, chemotherapy drugs, and light. Combined, this project aims to establish the field of ‘Acousto-Bioelectronics’ that spurs new theory and understanding for the next generation of IMDs. Furthermore, the project integrates the research with educational venues by mentoring graduate and undergraduate students, with a particular emphasis on the underrepresented minorities and female students, developing interdisciplinary curricula, and creating pedagogical resources ranging from fundamental theory to hands-on activities.While IMDs are transforming modern healthcare, they are unable to cure cancer at the moment due to their short lifetime. This is compounded by the fact that many cancers can relapse or spread metastatically. The overarching goal of this CAREER project is to leverage cross-cutting innovations from the domain of engineering and healthcare fields to create an ultrasonically-powered implantable microsystem that enables a tailored combination of multimodal cancer therapies. This study (1) elucidates the untapped potential of Platonic solid structures for a highly efficient omnidirectional ultrasonic powering scheme for IMDs, utilizing a unique 3D-printable barium titanate ultrasonic receiver. (2) Providing adequate power via ultrasound, the microsystem enables the in-situ generation of oxygen, cisplatin, and light through controlled electrochemical and photochemical processes. It is hence called Oxygen Enhanced Chemo-Photodynamic Therapy. (3) The microsystem can potentially realize clinically-proven superadditive anticancer effect – stronger than any single therapy or theoretical combination. The microsystem-mediated multimodal cancer therapy would be validated through a comprehensive evaluation by employing clinically relevant models (in vitro and in vivo cancer models). The outcome of this project justifies the development of the IMD-mediated multimodal cancer therapy that will potentially help patients suffering from aggressive and fatal cancer types with limited treatment alternatives.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.