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

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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.