Scientists make breakthrough in medical imaging and drug delivery with ultrasmall nanobubbles
Rice University bioengineers have developed the smallest free-floating gas-filled structures for medical imaging, potentially revolutionising ultrasound technology and targeted drug delivery.
Rice University researchers have engineered ultrasmall, stable gas-filled protein nanostructures that could transform ultrasound imaging and drug delivery methods. These novel diamond-shaped 50-nanometre gas vesicles (50-NM GVs) are believed to be the smallest stable, free-floating structures ever created for medical imaging purposes. Their minuscule size, comparable to that of viruses, allows them to cross biological barriers that have long posed challenges for larger microbubbles, opening up new possibilities for targeted therapies and diagnostic techniques.
Their research is published in Advanced Materials [1].
Overcoming size limitations
Current microbubbles used in ultrasound imaging and drug delivery typically range from 1 to 10 micrometres in diameter. While these have shown promise in recent advances, their large size restricts their movement primarily to the bloodstream, limiting their effectiveness to well-vascularised tissues.
The newly developed 50-NM GVs, however, can penetrate deeper into tissues. The research demonstrates that these nanobubbles can reach crucial immune cell populations in lymph nodes, a feat previously unattainable with larger contrast agents. George Lu, assistant professor of bioengineering at Rice University and a Cancer Prevention and Research Institute of Texas Scholar, explained the significance of this breakthrough: “This work represents a pioneering design of functional gas-filled protein nanostructures small enough to cross into the lymphatic system. The rationale was to harness their small size and acoustic properties for biomedical applications.”
Implications for cancer and infectious disease treatment
The ability of these nanobubbles to access lymph nodes has far-reaching implications for medical research and treatment. Electron microscopy images revealed large clusters of these nanostructures inside cells that play a critical role in activating the innate immune response.
“This breakthrough opens new avenues for ultrasound-mediated disease treatment, impacting future medical practices and patient outcomes,” Lu said. “The research has notable implications for treating cancers and infectious diseases, as lymph-node-resident cells are critical targets for immunotherapies.” The study employed a range of advanced techniques to develop and analyse these nanostructures. Methods included genetic engineering, nanoparticle characterisation techniques, electron microscopy, and ultrasound imaging to examine the distribution and acoustic response of the 50-NM GVs.
A biogenic approach
One of the most intriguing aspects of this research is the nature of the nanostructures themselves. Unlike synthetic materials, these nanobubbles are composed entirely of proteins and are produced within living bacteria.Lu highlighted this unique characteristic: “Because these nanostructures are composed entirely of proteins and are produced within living bacteria, they exemplify how biogenic materials can surpass the performance of synthetic materials.” While the initial results are promising, the researchers acknowledge that further investigation is necessary. Future research directions include:
1. Assessing the biosafety and immunogenicity of the nanobubbles
2. Determining optimal ultrasound parameters for in vivo applications
3. Exploring potential applications beyond medical imaging and drug delivery
Broader implications
The development of these ultrasmall nanobubbles represents more than just an advancement in medical technology. It signifies a leap forward in material design that could have ramifications across various scientific disciplines. As Lu noted: “More broadly, this represents a significant advancement in material design, potentially leading to innovative applications across various scientific fields.” The creation of these 50-nanometre gas vesicles marks a significant milestone in the field of medical imaging and drug delivery. By overcoming the size limitations of current microbubbles, this innovation opens up new possibilities for targeted therapies, particularly in the realms of cancer treatment and infectious disease management. As research progresses, these tiny bubbles could have an outsized impact on the future of medical diagnostics and treatment.
Reference:
1. Shen, Q., Li, Z., Wang, Y., et. al. (2024). 50-nm Gas-Filled Protein Nanostructures to Enable the Access of Lymphatic Cells by Ultrasound Technologies. Advanced Materials.
https://doi.org/10.1002/adma.202307123
George Lu (left) and Zongru Li
Photo credit: Anna Stafford/Rice University
