July 12, 2024

Modular Nanoparticles Developed for Precise Drug Delivery and Neutralization of Biological Agents

Researchers at the University of California San Diego have created modular nanoparticles that can be customized to target different biological entities such as tumors, viruses, or toxins. These nanoparticles have a surface that can be engineered to host various biological molecules, allowing for a wide range of applications including targeted drug delivery and neutralizing biological agents.

The innovation lies in the simplicity and efficiency of the technology. Instead of creating new nanoparticles for each specific purpose, researchers can use a modular nanoparticle base and easily attach proteins that target the desired biological entity. Previously, creating distinct nanoparticles for different biological targets required a separate synthetic process for each application. However, this new technique allows for the modification of the same modular nanoparticle base to create a range of specialized nanoparticles.

The modular nanoparticles are made up of biodegradable polymer cores that are coated with genetically modified cell membranes. The design incorporates a pair of synthetic proteins called SpyCatcher and SpyTag, which have the unique ability to spontaneously and exclusively bind with each other. This pairing is commonly used in biological research to combine various proteins. In this study, the researchers utilized SpyCatcher and SpyTag to create a system for easily attaching proteins of interest to the surface of the nanoparticles.

The process is as follows: SpyCatcher is embedded onto the nanoparticle surface, while SpyTag is chemically linked to a protein that targets specific tumors or viruses. When SpyTag-linked proteins come into contact with SpyCatcher-decorated nanoparticles, they bind to each other, allowing proteins of interest to be effortlessly attached to the nanoparticle surface. For example, to target tumors, SpyTag can be linked to a protein designed to seek out tumor cells, and that SpyTag-linked protein can then be attached to the nanoparticle. If the target shifts to a specific virus, the process is similarly straightforward: link SpyTag to a protein that targets the virus and attach it to the nanoparticle surface.

This streamlined approach to functionalizing nanoparticles for various biological applications is simple and effective, according to the researchers.

To create the modular nanoparticles, the researchers genetically engineered human embryonic kidney (HEK) 293 cells, a commonly used cell line in biological research, to express SpyCatcher proteins on their surface. The cell membranes were then isolated, broken into smaller pieces, and coated onto biodegradable polymer nanoparticles.

In a proof-of-concept study, the researchers tested these nanoparticles on mice with ovarian tumors. The nanoparticles were loaded with docetaxel, a chemotherapy drug, and administered to the mice via intravenous injection every three days for a total of four injections. The treatment with these nanoparticles resulted in suppressed tumor growth and improved survival rates. Treated mice had a median survival of 63 to 71 days, while untreated mice had a median survival of 24 to 29 days.

The researchers are now focused on further improving the modular nanoparticle platform for targeted drug delivery.

Aside from cancer treatment, the researchers are also excited about the potential applications of this technology. By utilizing the modular nanoparticle base, it is possible to attach a neutralizing agent on the surface to neutralize viruses and biological toxins. Additionally, there is potential for creating vaccines by attaching an antigen on the nanoparticle surface using this modular platform. This opens up various possibilities for new therapeutic approaches.


1. Source: Coherent Market Insights, Public sources, Desk research
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