Li, H. R. | bioRxiv Science

bioRxiv2025

A modular method for rapidly prototyping targeted gas vesicle protein nanoparticles

Gas vesicles (GVs) are air-filled protein nanoparticles which are proving to be useful in a number of biomedical applications. We hypothesized that it could be possible to develop a modular method for creating rapidly prototyped GVs by modifying their surface chemistry to include targeting peptides in an orientation-specific manner. Here, we describe a modular method to create targeted GVs using His-tagged antibody fragments, ensuring that the antibody fragments are connected to the GV in an orientation-specific manner. This is achieved via the functionalization of the GVs with nickel-nitrilotriacetic acid (Ni-NTA) group. First, we validated that these functionalized GVs can bind His-tagged green fluorescent protein and characterized the particle size and surface charge of functionalized GVs. Then, GVs targeted to prostate-specific membrane antigen (PSMA) using a minibody were validated using a knockout validation in vitro.

bioengineering↗

bioRxiv2024

Acoustic tumor paint for real-time imaging, surgical guidance and recurrence monitoring of brain tumors with ultrasound

The rapid growth, invasiveness, and resistance to treatment of glioblastoma multiforme (GBM) underscore the urgent need for improved diagnostics and therapies. Current surgical practice is limited by challenges with intraoperative imaging, while recurrence monitoring requires expensive magnetic resonance or nuclear imaging scans. Here we introduce "acoustic tumor paint", an approach to labeling brain tumors for ultrasound imaging - a widely accessible imaging modality. We show that gas vesicles (GVs), natural air-filled protein nanostructures, preferentially accumulate in brain tumors following systemic administration in syngeneic and xenograft mouse models of GBM. This enables real-time tumor visualization during surgery and postoperative monitoring of recurrence. We characterize GV uptake and breakdown by tumors and their resident cells and support clinical translatability by documenting non-toxic repeated administration. We also demonstrate the potential for post-operative monitoring in humans by imaging GVs through a human skull and an FDA-approved skull prosthesis. Acoustic tumor paint has the potential to enhance diagnostic accuracy, improve surgical outcomes, make monitoring more accessible, and extend survival in GBM patients.

bioengineering↗