Investigating Laser-Activation of Structured Polymer Materials for Drug Delivery

研究用于药物输送的结构化聚合物材料的激光激活

• 批准号: 1806434
• 负责人: Eric Mazur
• 金额: $ 83.06万
• 依托单位: Harvard University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1806434&HistoricalAwards=false
• 关键词: Investigating; Laser; Activation; Structured; Polymer

The PI recently discovered that laser-activation of certain polymers performs effective cargo delivery. As polymers are biocompatible, cheap, and easily integrated, the work in this project plans to leverage this recent (unexpected, and as-of-yet not understood) discovery to fabricate and characterize laser-activated polymers, with the aim of better equipping the biomedical field with novel in vivo cargo-delivery methods that harness laser-activated materials. While advancing discovery, the work will also contribute to the education and the training of future multidisciplinary scientists and engineers through research-based education of undergraduate and graduate students. Through the Mazur Group's work with local high schools, NSF sponsored programs, and the high representation of women in his research group, they will broaden participation of underrepresented groups. Finally, using the group's well-established program integrating outreach and public education with research, this work will be broadly disseminated to the general public.This project is for investigating the newly discovered phenomenon of laser-activation of polymers with an eye toward developing light-activated polymer materials that are flexible in structure, patterned, biodegradable, and easy to implant into the body, unlike traditional metallic nanofabricated substrates, for the delivery of payloads into cells. The goals of this project are to: 1) study the fundamental physics of the light-matter interactions of these polymer materials and cells; and 2) develop and apply these light-activated polymer materials for biomedical engineering applications. Developing new approaches for cell therapy and regenerative medicine, as well as studying modified gene expression, requires efficient and safe introduction of genetic vectors into mammalian cells. There is a biomedical need for gene delivery modalities that are efficient and non-toxic and that and can treat a large number of cells in a short amount of time. Being able to have a highly efficient cargo delivery method while maintaining cell viability and medically relevant treatment throughput would revolutionize nanomedicine and open the door to new cell therapies and regenerative medicine. In summary, this project focuses on studying the fundamental physics of light-matter interaction of various structures composed of polymer and bioplastic materials and properties in a liquid environment. The motivation is to create a flexible and biocompatible platform for transfection in implantable materials. It is important to characterize material properties to determine how biocompatible and viable these materials may be for different sensitive cell types. Developing a strong design and understanding of a new biomaterial will open avenues to trigger delivery in a non-invasive manner using light-activation within a patient. Due to the ease of fabrication and scalability of structured polymer surfaces to be used in this project, there is great potential to maximize throughput for clinical applications. This proposed research could be truly transformative to the field of cargo delivery and provide an enormous opportunity for active implants. Beyond demonstrating cargo delivery with laser-activated structured polymer and bioplastic materials and their use in biomedical applications, the work will also explore several fundamental topics as follows: (1) identifying what effects govern successful light-polymer interaction for cell poration; (2) characterizing the pressure wave perturbation and bubble formation, when excited with different types of laser (pulsed and continuous wave) on structured polymer materials through experimental measurements; (3) establishing guidelines for designing a wide variety of structured polymer and bioplastic materials; and (4) identifying properties that dictate favorable cell attachment to these structured materials.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.

PI最近发现，某些聚合物的激光激活可以有效地运送货物。由于聚合物具有生物相容性，廉价且易于集成，因此该项目中的工作计划利用这一最新（意想不到的，尚未理解的）发现来制造和表征激光活化聚合物，目的是更好地为生物医学领域提供利用激光活化材料的新型体内货物递送方法。 在推进发现的同时，这项工作还将通过对本科生和研究生的研究型教育，为未来多学科科学家和工程师的教育和培训做出贡献。通过马祖尔集团与当地高中的合作，NSF赞助的项目，以及妇女在他的研究小组中的高代表性，他们将扩大代表性不足的群体的参与。最后，本计画将透过本研究所的外展、教育与研究相结合的计画，将这项研究成果广泛地传播给大众。本计画是研究高分子的雷射活化新现象，并着眼于开发结构灵活、图案化、可生物分解、易于植入体内的光活化高分子材料，与传统的金属纳米制造基底不同，用于将有效载荷递送到细胞中。该项目的目标是：1）研究这些聚合物材料和细胞的光-物质相互作用的基础物理; 2）开发和应用这些光激活聚合物材料用于生物医学工程应用。开发细胞治疗和再生医学的新方法，以及研究修饰的基因表达，需要将遗传载体有效和安全地引入哺乳动物细胞。生物医学上需要高效且无毒的基因递送方式，并且可以在短时间内处理大量细胞。能够拥有高效的货物递送方法，同时保持细胞活力和医学相关的治疗通量，将彻底改变纳米医学，并为新的细胞疗法和再生医学打开大门。总之，该项目的重点是研究由聚合物和生物塑料材料组成的各种结构的光-物质相互作用的基础物理学以及在液体环境中的性质。其动机是创造一个灵活的和生物相容的平台，用于在可植入材料中转染。重要的是表征材料特性，以确定这些材料对于不同敏感细胞类型的生物相容性和可行性。开发强大的设计和对新生物材料的理解将为在患者体内使用光激活以非侵入性方式触发递送开辟道路。由于该项目中使用的结构化聚合物表面易于制造和可扩展性，因此有很大的潜力使临床应用的吞吐量最大化。这项拟议中的研究可能对货物运输领域产生真正的变革，并为主动植入物提供巨大的机会。除了展示激光激活结构聚合物和生物塑料材料的货物输送及其在生物医学应用中的应用外，这项工作还将探索以下几个基本主题：（1）确定什么影响了成功的光-聚合物相互作用，用于细胞穿孔;（2）表征压力波扰动和气泡形成，当用不同类型的激光激发时（3）建立用于设计各种各样的结构化聚合物和生物塑料材料的准则;以及（4）确定决定细胞与这些结构材料良好附着的特性。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。