Nanoparticles for targeted delivery
Our laboratory has historically been involved in designing peptide-based delivery vehicles to route therapeutics to and into cells. More recently, we have developed a rapid approach to develop tumor-targeted nanoparticles displaying both a diagnostic and a therapeutic function. These nanoparticles are acoustically active (echogenic), meaning that their movement that be followed (imaged) using ultrasound waves (US).
What is a gas vesicle ?
Gas vesicles (GVs) are naturally-occurring air-filled, protein nanoparticles that are being repurposed to serve as potential echogenic theranostic agents.
Figure 1. TEM image of gas vesicle from Halobacterium salinarum strain NRC-1
How to potentially use gas vesicles ?
Introducing a tumor targeting function on their surface would enhance their tumor imaging and therapeutic value. Herein, we have developed a non-covalent strategy to universally target Halobacterium salinarum GVs, weaponized with the photoreactive agent chlorin e6 (Ce6-GVs) to guide their delivery to tumor cells.
Specifically, four murine monoclonal antibodies were generated that bind tightly to GvpA, the major protein component forming the GV shell. A bispecific adapter protein, termed MFE-23-ZZ, was also constructed incorporating MFE-23, a murine scFv fragment that recognizes the cancer-associated human carcinoembryonic antigen (CEA) with high affinity fused to a Protein ZZ domain, which binds to the Fc region of murine and human IgGs. The adapter protein MFE-23-ZZ readily formed complexes with anti-GvpA-decorated Ce6-GVs.
The resulting tripartite complexes termed MFE-23-ZZ-mAb2B10-1-Ce6-GVs enhanced the intracellular uptake of Ce6-GVs into murine MC38.CEA colon carcinoma cells expressing human CEA relative to the CEA-parental cell line MC38, as monitored by flow cytometry. Furthermore, MC38.CEA cells exposed to MFE-23-ZZ-mAb2B10-1-Ce6-GV complexes were one order of magnitude more sensitive to light exposure (660 nm) and displayed higher levels of reactive oxygen species due to chlorin e6 activation than the parental CEA- MC38 cells.
Collectively, these results suggest that the surface of nanoparticles such as gas vesicles can be rapidly and non-covalently functionalized to target tumor cells, increasing their potential as both therapeutic and diagnostic agents.
Figure 2. Graphic summary of gas vesicle theranostic strategy employed by our laboratory.
Last updated on Nov-4-2021