
NSF Org: |
DMR Division Of Materials Research |
Recipient: |
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Initial Amendment Date: | May 20, 2019 |
Latest Amendment Date: | April 24, 2023 |
Award Number: | 1845683 |
Award Instrument: | Continuing Grant |
Program Manager: |
Nitsa Rosenzweig
nirosenz@nsf.gov (703)292-7256 DMR Division Of Materials Research MPS Directorate for Mathematical and Physical Sciences |
Start Date: | June 15, 2019 |
End Date: | November 30, 2024 (Estimated) |
Total Intended Award Amount: | $543,136.00 |
Total Awarded Amount to Date: | $543,136.00 |
Funds Obligated to Date: |
FY 2020 = $103,372.00 FY 2021 = $102,776.00 FY 2022 = $110,912.00 FY 2023 = $115,426.00 |
History of Investigator: |
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Recipient Sponsored Research Office: |
9500 GILMAN DR LA JOLLA CA US 92093-0021 (858)534-4896 |
Sponsor Congressional District: |
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Primary Place of Performance: |
CA US 92093-0934 |
Primary Place of
Performance Congressional District: |
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Unique Entity Identifier (UEI): |
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Parent UEI: |
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NSF Program(s): | BIOMATERIALS PROGRAM |
Primary Program Source: |
01002021DB NSF RESEARCH & RELATED ACTIVIT 01002122DB NSF RESEARCH & RELATED ACTIVIT 01002223DB NSF RESEARCH & RELATED ACTIVIT 01002324DB NSF RESEARCH & RELATED ACTIVIT |
Program Reference Code(s): |
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Program Element Code(s): |
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Award Agency Code: | 4900 |
Fund Agency Code: | 4900 |
Assistance Listing Number(s): | 47.049 |
ABSTRACT
Technical Abstract
The 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 Abstract
This 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.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
Project Outcomes
This project created innovative materials for biomedical applications by designing biodegradable nanomaterials capable of imaging, drug delivery, and cancer therapy. Our goal was to create systems that could address critical limitations in current diagnostic and therapeutic technologies—specifically, poor biodegradability, limited targeting capability, and insufficient immune activation. The outcome for taxpayers is cancer imaging agents and therapies that work better.
We focused on calcium phosphate-based materials, which are well-known for their biocompatibility and ability to dissolve safely in the body. One major breakthrough was the development of hydro-expandable calcium phosphate particles that can grow dramatically in size (up to 720% in volume) when hydrated. This swelling property enables a novel method of mechanically disrupting targeted cells or tissue, providing a non-toxic, localized alternative to conventional drug-based ablation. These particles are synthesized using a low-temperature sol-gel and electrospray process that enables precise control over their size and morphology—from flower-like to smooth spherical particles—unlocking new directions in particle-based therapies.
Another component of our work involved a bio-inspired approach that mimics natural processes like biosilicification in diatoms. We created a mild, solution-based method to synthesize degradable composites of polyethylenimine (PEI) and calcium phosphate. These composites could be tuned in size from nanometers to microns and demonstrated strong ultrasound and optical imaging signals. Importantly, these imaging agents degrade within 24 hours, overcoming the persistent toxicity associated with many inorganic imaging agents, and offering a transient but powerful tool for medical imaging.
We also engineered a series of “proton sponge nano-assemblies” that self-assemble to enhance surface charge and selectively rupture lysosomes inside cancer cells. These assemblies are built from small, low-toxicity components that become highly active only upon assembly—making them safer and more targeted. They triggered a form of cancer cell death known as immunogenic cell death, which not only destroys the tumor cells but also activates the immune system to recognize and attack the tumor. This approach offers a promising strategy to turn “immune-cold” tumors into “immune-hot” environments that are more responsive to immunotherapy.
Intellectual Merit
This work made foundational contributions to the chemistry and nanotechnology of biodegradable materials. We developed new methods for synthesizing tunable nano/micro structures using mild conditions compatible with biological molecules. We also provided the first detailed study of hydro-expansion in phosphate glasses and identified mechanisms of lysosome-triggered cell death using designer proton sponge assemblies. These findings contribute to the fundamental understanding of how structure, surface charge, and degradability affect the behavior of nanomaterials in biological environments.
Broader Impacts
The project has direct implications for improving healthcare outcomes. By creating biodegradable, non-toxic imaging agents and therapeutic systems, we provide alternatives to persistent inorganic materials that can cause long-term side effects. Our cancer-targeting materials offer potential improvements to immunotherapy by making tumors more responsive to treatment. These advances could lead to safer diagnostics, more effective localized therapies, and better patient outcomes.
The project also involved interdisciplinary training for graduate and undergraduate researchers in chemistry, bioengineering, materials science, and nanomedicine. Several publications resulted from this work, and the methodologies developed are now being applied to other diseases and delivery platforms. We volunteered at science fairs to teach elementary school children about how ultrasound works—this is important in the context of workforce development.
Last Modified: 03/21/2025
Modified by: Jesse V Jokerst
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