CAREER: Tailoring Thermal Conductivity of Soft Magnetic Nanomaterials for Wireless Neuromodulation

神经系统疾病和精神疾病的治疗需要精确控制神经细胞信号；然而，现有的控制神经活动的技术缺乏特异性或对脑组织造成损害，导致不良的副作用。这个NSF CAREER项目旨在开发一种新的纳米技术，以选择性地控制神经活动，用于下一代脑功能障碍治疗，例如癫痫的治疗。该项目将(1)为精确控制神经活动提供一个全新的范例，(2)为研究界提供一个绘制大脑回路的新平台，以提高我们对复杂神经网络的理解，(3)使下一代治疗所需药物的按需本地化释放成为可能，(4)加速治疗脑功能障碍的无线技术的发展。作为教育目标的一部分，将该研究整合到旨在提高学生兴趣和提高STEM领域表现的教育计划中，研究者将(1)开发新的以学生为中心的学习活动，以促进本科生物传输现象教育中的元认知（“学会学习”），(2)为当地高中教师提供纳米尺度热量和质量传输的研究机会和培训。(3)为圣安东尼奥约2000名当地高中学生创建符合发展标准的高中活动和课程；(4)通过在学术界扮演拉丁裔榜样的角色，继续招募和指导工程领域代表性不足的少数族裔学生。研究者的长期研究目标是建立一个创新和富有成效的研究计划，研究纳米尺度的传输现象原理，以发展新的神经调节和新的纳米技术平台，彻底改变神经网络的精确控制。为了实现这一目标，该CAREER项目将开发一种软磁纳米材料平台，通过将交变磁场转化为化学刺激，实现稳定的药理、无毒、可靶向的神经调节策略。该项目需要一种技术来唤起和抑制神经活动的需求，以了解神经回路动力学的基本生物学，考虑细胞类型的特异性，但不需要药物制剂，转基因的传递，或对生物组织有害的植入式装置。这将通过表面工程磁性纳米颗粒（MNPs）与生物相容性温度响应聚合物刷负载神经调节化合物来实现。MNPs在交变磁场（AMFs）下产生的热量将触发其聚合物涂层的构象变化，释放负载的神经调节剂。神经调节化合物的局部释放将增强或抑制特定的细胞膜受体诱导神经去极化。该系统将被用于研究癫痫发作的可能管理，通过靶向细胞膜的MNPs局部释放维拉帕米和bay-K8644，按需调节海马神经活动。研究计划有三个目标：(1)研究生物相容性温度响应聚合物刷的合成和表征；(2)研究磁性纳米颗粒表面聚合物刷涂层对神经调节化合物的包裹及其按需释放；(3)为神经活动的精确调节设计磁热药理学范式。该奖项反映了美国国家科学基金会的法定使命，并通过基金会的智力价值和更广泛的影响审查标准进行评估，认为值得支持。

The treatment of neurological disorders and psychiatric conditions requires precise control of neural cell signaling; however, existing technologies to control neural activity lack specificity or are damaging to brain tissues, causing undesirable side effects. This NSF CAREER project aims to develop a new nanotechnology to selectively control neural activity for the next generation of brain malfunction therapies, e.g., the treatment of epilepsy. The project will (1) lead to a completely new paradigm for the precise control of neural activity, (2) provide the research community with a new platform for mapping brain circuits to improve our understanding of complex neural networks, (3) enable the on-demand localized release of drugs required for the next generation of therapies, and (4) accelerate the development of wireless technologies for the treatment of brain malfunctions. As part of an education objective to integrate this research into an educational program designed to increase student interest and improve performance in STEM fields, the investigator will (1) develop new student-centered learning activities to promote metacognition (“learning to learn”) in undergraduate Biotransport Phenomena education, (2) provide research access and training in nanoscale heat and mass transport to local high school teachers, (3) create developmentally appropriate standards-based high school activities and lessons reaching to approximately 2,000 local high school students in San Antonio and (4) continue to recruit and mentor underrepresented minority students in engineering by serving as a Latina role model in academia.The investigator’s long-term research goal is to build an innovative and productive research program to investigate nanoscale transport phenomena principles for the development of novel neuromodulation and new nanotechnological platforms to revolutionize the precise control of neural networks. Toward this goal, this CAREER project will develop a soft magnetic nanomaterials platform to enable a stable pharmacological, non-toxic, targetable strategy for neuromodulation by transducing alternating magnetic fields into chemical stimulus. The project addresses the need for a technique for evoking and inhibiting neural activity on demand to understand the basic biology of neural circuit dynamics that considers cell-type specificity but does not require pharmacological agents, delivery of transgenes, or implantable devices that are damaging to biological tissue. This will be accomplished by surface engineering magnetic nanoparticles (MNPs) with biocompatible temperature responsive polymer brushes loaded with neuromodulatory compounds. The heat generated by the MNPs under alternating magnetic fields (AMFs) will trigger conformational changes in their polymer coating releasing loaded neuromodulators. The local release of neuromodulatory compounds will enhance or inhibit specific cell membrane receptors inducing neural depolarization. The system will be investigated for the possible management of epileptic seizures by modulating hippocampal neural activity on-demand through the local release of verapamil and bay-K8644 from MNPs targeted to the cell membrane. The research plan is organized under three aims: (1) Investigate the synthesis and characterization of biocompatible temperature-responsive polymer brushes, (2) Investigate polymer brushes coatings on magnetic nanoparticles surface for the entrapment of neuromodulatory compounds and its on-demand release, and (3) Design a magnetothermal pharmacological paradigm for precise modulation of neural activity,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.