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.

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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.

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Figure 2. Graphic summary of gas vesicle theranostic strategy employed by our laboratory.

Selected publication from our group:

1. Fernando A and Gariépy J (2020) Coupling Chlorin e6 to the surface of Nanoscale Gas Vesicles strongly enhance their intracellular delivery and photodynamic killing of cancer cells. Sci Rep. 10:2802

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Last updated on Nov-4-2021