ERI: Nanoscale Photo-Magnetic Energy Transfer Modulation to Restore the Homeostatic Functioning of the Damaged Endothelium

ERI：纳米级光磁能量转移调节以恢复受损内皮的稳态功能

• 批准号: 2301688
• 负责人: Santaneel Ghosh
• 金额: $ 19.99万
• 依托单位: Southeast Missouri State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2301688&HistoricalAwards=false
• 关键词: ERI; Nanoscale; Photo; Magnetic; Energy

Endothelial cells, which line the walls of the blood vessels, are subject to significant stress in a variety of conditions, including diabetes and various inflammatory diseases. This condition massively increases risk for cardiovascular diseases associated with high rates of morbidity and mortality. Current noninvasive approaches lack effective and targeted damage repair. Light therapy, when administered through a particular radiation mode, can extract significant advantages, and thus, is often considered a noninvasive therapeutic approach in regenerative medicine. Nanostructures made from materials with magnetic properties are attractive possibilities for designing novel platforms for similar applications. Thus, it may be possible to enhance the effectiveness of these approaches by aptly combining the optical and the magnetic excitation for tissue repair. In this project, the PI will use simultaneous optical-magnetic stimulation to the targeted cells in combination with the delivery of energy-harvesting nanodevices to create a novel therapeutic approach. The knowledge derived from this research will directly contribute towards reliable platforms for high-throughput screening of pharmaceutical or toxicological agents and their effects on cardiovascular diseases. Additionally, the societal impacts are broad since this research derived technique will be useful to release a combination of therapeutic agents plus infection preventing molecules simultaneously from a drug reservoir. In the middle of an ongoing pandemic or in future situations like this, where infection prevention is of supreme importance in conjunction with the critical care, this will be extremely useful to conduct efficacy assessment on selected drugs. The project, due to its inter-disciplinary nature, will involve students from multiple fields of science and technology. Students, especially those under-represented within STEM fields, will be recruited, and supported to boost the research and innovation culture of the institution. The students involved in the project will be exposed to a wide range of perspectives and ideas, thus fostering diversity. Chronic oxidative stress exposure of the endothelium leading to depletion of intracellular energy and, therefore, induction of apoptosis, which massively increases the risk for cardiovascular diseases, is a significant health problem. Mechanisms to re-establish normal endothelium functioning and induce cell growth and proliferation following chronic oxidative damage are complex and still not well understood. The understanding of these processes is important towards comprehensive control to treat the diseases that involve endothelium damage. Introduction of combinatorial therapeutics consisting of synergistic photo-magnetic stimulation, and multifunctional nanoscale energy-harvesting devices that are biocompatible, remotely tunable, and capable of performing on-demand release of a specific drug or a combination of drugs to the targeted cells can revolutionize the treatment outcomes for diseases that involve endothelium damage. This research, by implementing an innovative multimodal comprehensive strategy that has been unexplored thus far – hybrid photo-magnetic stimulation – will focus on synergistically modulating the intracellular pathways to restore homeostatic functioning of the endothelium following the induction of oxidative stress. In this project, the primary objectives will be: (a) Introduce molecular level energy-harvesting devices to provide photo-magnetic and chemical cues; (b) Determine whether the combinatorial photo-magnetic therapy can restore homeostatic functioning of the endothelium following induction of oxidative stress; and (c) Explore the cellular and molecular mechanism(s) by which the photo-magnetic combinatorial therapeutics would reverse the endothelium damage. Opto-magnetically responsive nanodevices will be encapsulated within a thermo-activated poly(ethylene glycol) based biopolymer network, which is non-toxic, and anti-immunogenic. The energy-harvesting devices will be targeted to cells by derivatizing the polymer shell with ligands for specific plasma membrane receptors. The cell-bound nanodevices, when placed inside the hybrid photo-magnetic excitation exposure, will perform the controlled release of small molecules that activate signal transduction pathways leading to endothelium damage repair, and convert the excitation energy to chemical potential for Adenosine triphosphate synthesis. Additionally, the hybrid photo-magnetic excitation strategy will permit the use of a less intense alternating current magnetic field in combination with optical stimulation during the irradiation process, thus removing the safety concerns associated with using only alternating current magnetic field assisted therapies. A unique approach of nanodevice and chemical cues integration with an opto-magnetic excitation strategy for endothelium damage repair will stimulate several technical fields, including cardiovascular disease monitoring, high-throughput screening of pharmaceutical or toxicological agents, and identification of potential effects on endothelium damage. The primary educational benefit of this project will be the interactions and direct participation of students at Southeast Missouri State University. Educational and outreach activities include training students in advanced instrumentation and conducting cross-listed courses, involving upper-level undergraduate and graduate students. In addition, research and educational activities of the project will be integrated with the current undergraduate educational efforts of the Ronald F. McNair post-baccalaureate achievement initiative at Southeast, which promotes research experiences among members of students under-represented in STEM fields.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.