CAREER: Expandable sol-gel nanomaterials as therapeutic tools and imaging agents

职业：可膨胀溶胶-凝胶纳米材料作为治疗工具和成像剂

• 批准号: 1845683
• 负责人: Jesse Jokerst
• 金额: $ 54.31万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1845683&HistoricalAwards=false
• 关键词: CAREER; Expandable; sol; gel; nanomaterials; CAREER; Expandable; sol; gel; nanomaterials

Technical AbstractThe long-term goal of this research is to develop novel biomaterials for medical imaging and therapy and to educate the public and future materials scientists about biomaterials research. The research objective is to create novel biomaterials with both imaging and therapeutic capabilities. Here, the PI will synthesize P2O5-CaO-Na2O phosphate sol-gel nanoparticles and will modulate the concentration of cations to control the structure-function properties including biodegradation time. One surprising feature of these materials is that they swell up to 500% larger during their biodegradation in aqueous environments. Thus, the PI hypothesizes that one can control this swelling by coating the nanoparticles with a responsive hydrophobic shell and use this size change to ablate cancer cells. By building the shell with site-selective cleavage sites, the nanoparticle core would be exposed to the cytosol and swell only in the presence of defined chemical cues. This swelling would then mechanically destroy the cells of interest. These materials also have an acoustic impedance mismatch with tissue and can report the cell killing process via ultrasound. The educational objective is to disseminate the research findings to the scientific community, graduate and undergraduate trainees, as well as high school students via focused seminars and hands-on training with a portable ultrasound scanner. The broader impacts of this CAREER award will focus on LGBTQ students who typically lack visibility and community in the STEM fields. The PI will offer mentorship connections, networking opportunities, and professional/leadership development for our LGBT STEM students.Non-Technical AbstractThis project is creating a biomaterial based on phosphate ions, which are a very common type of salt in the human body. The PI will create very small particles of this phosphate-based biomaterial and use it to image and treat cancer. The remarkable feature of this biomaterial is that it swells when it degrades-size changes up to 5-fold were shown in preliminary data. This is useful because when these materials swell inside of cancer cells, they will destroy the dangerous tissue. This project will design the particles such that they only swell in the presence of biomarkers found on the surface of the cancer cells to prevent damage to other cells. A second important feature of this idea is that doctors can image the location of the particles with ultrasound. This is because sound waves will echo off the surface of the particles. Importantly, as the particles swell, even more sound waves will be reflected. Thus, doctors can use the images to understand the location of the particles and whether they have been activated by the cancer cells or not. The benefit to society will be a less traumatic and more effective cancer treatment, which includes an imaging signal physicians can use to customize treatment. These efforts will also educate the next generation of engineers and scientists using hands-on ultrasound modules in the teaching labs at UC San Diego.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.

技术摘要这项研究的长期目标是开发用于医学成像和治疗的新型生物材料，并教育公众和未来的材料科学家有关生物材料研究的研究。研究目标是通过成像和治疗能力来创建新型的生物材料。在这里，PI将合成P2O5-CAO-NA2O磷酸溶胶 - 凝胶纳米颗粒，并将调节阳离子的浓度，以控制包括生物降解时间在内的结构功能。这些材料的一个令人惊讶的特征是，在水性环境中，它们在生物降解过程中膨胀了500％。因此，PI假设可以通过用响应式疏水性壳涂纳米颗粒来控制这种肿胀，并将这种尺寸的变化变化以消融癌细胞。通过使用位点选择性切割位点构建壳，纳米颗粒芯只能在存在定义的化学提示的情况下暴露于细胞质和膨胀。然后，这种肿胀会机械地破坏感兴趣的细胞。这些材料还与组织具有声阻抗不匹配，可以通过超声报告细胞杀死过程。教育目标是通过专注的研讨会和便携式超声扫描仪通过专注的研讨会和动手培训将研究结果传播给科学界，研究生和本科学员，以及高中生。该职业奖的更广泛影响将集中于通常缺乏STEM领域知名度和社区的LGBTQ学生。 PI将为我们的LGBT STEM学生提供指导连接，网络机会和专业/领导力开发。Non-technical Abstrack This This Turnis Project正在创建基于磷酸盐离子的生物材料，这是人体中非常普遍的盐类型。 PI将产生这种基于磷酸盐的生物材料的非常小的颗粒，并将其用于形象和治疗癌症。这种生物材料的显着特征是，在初步数据中显示了降解大小的变化最多5倍时膨胀。这很有用，因为当这些材料在癌细胞内部膨胀时，它们会破坏危险的组织。该项目将设计颗粒，使它们仅在癌细胞表面存在的生物标志物存在下膨胀，以防止对其他细胞的损害。这个想法的第二个重要特征是，医生可以超声检查颗粒的位置。这是因为声波会在颗粒的表面上回荡。重要的是，随着颗粒膨胀，会反映更多的声波。因此，医生可以使用图像来了解颗粒的位置以及它们是否被癌细胞激活。对社会的好处将是一种不太创伤和更有效的癌症治疗方法，其中包括成像信号医生可以用来定制治疗。这些努力还将在圣地亚哥分校的教学实验室中使用动手超声模块来教育下一代工程师和科学家。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子的评估来支持的，并具有更广泛的影响。