Antibody-loading of biological nanocarrier vesicles derived from red-blood-cell membranes

Antibodies are powerful tools in modern medicine, capable of targeting and neutralizing specific pharmacological threats with high precision. However, their effectiveness is often hampered by the difficulty of delivering them past the body’s immune defenses and into cells where they can do their work. To overcome these barriers, scientists have explored various methods such as using liposomes or nanoparticles disguised with biological molecules. Now, an innovative approach developed by researchers at the KTH Royal Institute of Technology using exosome-mimetic nanovesicles derived from human red blood cell membranes offers a promising new solution.

What Are Exosome-Mimetic Nanovesicles?

Exosomes are tiny vesicles naturally released by cells that play a crucial role in cell-to-cell communication. Researchers have discovered that they can create artificial versions of these vesicles, known as exosome-mimetic nanovesicles, using membranes from human red blood cells. These bioengineered nanovesicles are particularly attractive for therapeutic use because they are biocompatible (safe for the body) and have low immunogenicity (unlikely to provoke an immune response).

Loading Antibodies into Nanovesicles

In this study, the scientists successfully loaded antibodies into these exosome-mimetic nanovesicles to test their potential as carriers for drug delivery. Specifically, they used goat anti-chicken antibodies and compared the loading efficiency with smaller molecules like dUTP (a component of DNA). They employed a technique called dual-color coincident fluorescence burst analysis to measure the loading yield at the single-vesicle level. This method allowed them to overcome the challenges posed by the size variability of the nanovesicles and accurately determine how many antibodies were successfully loaded.

(a) Preparation steps of antibody-loaded nanovesicles. Ab = antibody, RBC = red blood cell nanovesicles, and RBC+ = RBC with additional solution cleaning. (b) Dual-color fluorescent staining scheme for the Ab cargo (Alexa488, green dye) and the nanovesicle (CellVue Claret, red dye). AFM: (c) experimental setup and (d) image of nanovesicles. DCFM: (e) setup and (f) typical time traces in detection for the red (vesicles) and the green (antibody molecules) signal channels. Coincident red and green temporal bursts denote Ab-loaded nanovesicles.

Key Findings

The optimal vesicle size for maximum antibody loading was found to be around 52 nanometers in radius. At this size, the loading yield of antibodies was between 38-41%. On average, across the entire population of nanovesicles, about 14% were successfully loaded with more than two antibodies per vesicle. This efficiency was comparable to that achieved with the much smaller dUTP molecules, even after additional purification steps.

Implications for Therapeutic Delivery

These findings suggest that exosome-mimetic nanovesicles derived from human red blood cell membranes could be a powerful new method for delivering antibodies into cells. This method could potentially be used to target intracellular threats, which are often difficult to reach with traditional therapies. Moreover, the approach is suitable for large-scale applications, offering a scalable solution for pharmaceutical development.

Conclusion

The ability to effectively load and deliver antibodies using exosome-mimetic nanovesicles represents a significant advancement in therapeutic delivery systems. This innovative approach harnesses the natural properties of human cell membranes to create a biocompatible and efficient carrier for antibodies, opening up new possibilities for treating a wide range of diseases at the cellular level. As research progresses, we may soon see these nanovesicles playing a crucial role in next-generation medical treatments, bringing us closer to more effective and targeted therapies.

Sanaee M, Ronquist KG, Sandberg E, Morrell M, Widengren J, Gallo K. (2024) Antibody-Loading of Biological Nanocarrier Vesicles Derived from Red-Blood-Cell Membranes. ACS Omega [Epub ahead of print]. [article]

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