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

本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关于生物材料的研究。研究目标是创造具有成像和治疗能力的新型生物材料。在这里，PI将合成P2 O 5-CaO-Na 2 O磷酸盐溶胶-凝胶纳米粒子，并将调节阳离子的浓度，以控制结构-功能特性，包括生物降解时间。这些材料的一个令人惊讶的特征是，它们在水性环境中的生物降解过程中膨胀高达500%。因此，PI假设可以通过用响应性疏水壳涂覆纳米颗粒来控制这种溶胀，并使用这种尺寸变化来消融癌细胞。通过构建具有位点选择性切割位点的壳，纳米颗粒核心将暴露于胞质溶胶并仅在存在限定的化学线索的情况下溶胀。然后，这种肿胀会机械地破坏感兴趣的细胞。这些材料还具有与组织的声阻抗失配，并且可以通过超声报告细胞杀伤过程。教育目标是通过重点研讨会和使用便携式超声波扫描仪的实践培训，向科学界、研究生和本科生学员以及高中生传播研究成果。这个职业奖的更广泛的影响将集中在LGBTQ学生谁通常缺乏知名度和社区在STEM领域。PI将为我们的LGBT STEM学生提供导师联系，网络机会和专业/领导力发展。非技术摘要该项目正在创建一种基于磷酸盐离子的生物材料，磷酸盐离子是人体中非常常见的一种盐。PI将创造这种磷酸盐基生物材料的非常小的颗粒，并将其用于成像和治疗癌症。这种生物材料的显著特点是降解时会膨胀，初步数据显示其尺寸变化高达5倍。这是有用的，因为当这些物质在癌细胞内膨胀时，它们会破坏危险的组织。该项目将设计这些颗粒，使它们只在癌细胞表面发现的生物标志物存在的情况下才会膨胀，以防止对其他细胞造成损害。这个想法的第二个重要特征是医生可以用超声波成像颗粒的位置。这是因为声波会从颗粒表面反射回来。重要的是，随着颗粒膨胀，更多的声波将被反射。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。对社会的好处将是创伤更小，更有效的癌症治疗，其中包括医生可以用来定制治疗的成像信号。这些努力也将教育下一代的工程师和科学家在教学实验室在加州大学圣地亚哥分校使用动手超声模块。这个奖项反映了NSF的法定使命，并已被认为是值得的支持，通过评估使用基金会的智力价值和更广泛的影响审查标准。

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.