Rapid On-Demand Extracellular Vesicle Augmentation with Versatile Oligonucleotide Tethers.

Area of Science:

• Biotechnology
• Nanomedicine
• Cell Biology

Background:

• Exosomes are natural intercellular carriers with potential for drug delivery.
• Current exosome engineering methods are complex, time-consuming, and inefficient.
• Existing techniques often negatively impact exosome function.

Purpose of the Study:

• To develop a rapid, versatile, and scalable method for exosome surface functionalization.
• To enhance exosome properties and enable targeted drug delivery.
• To demonstrate the therapeutic potential of engineered exosomes.

Main Methods:

• Utilized oligonucleotide tethers for exosome surface modification.
• Applied diverse surface modifiers including aptamers, proteins, and functional groups.
• Functionalized exosomes with AS1411 aptamer for altered cellular uptake and FasL protein for immunomodulation.
• Bioprinted FasL-exosomes on collagen matrices and injected them into mice.

Main Results:

• Demonstrated rapid and efficient exosome surface functionalization on human and murine exosomes.
• Showcased specific alteration of cellular uptake via AS1411 aptamer tethering.
• Confirmed targeting specificity modification using a tethered protein.
• Validated in vitro and in vivo biological activity of FasL-functionalized exosomes, including spatial tumor cell apoptosis and T cell proliferation suppression.

Conclusions:

• Oligonucleotide tethering offers a versatile and scalable approach for exosome engineering.
• This method circumvents the need for genetic modification of exosome-secreting cells.
• Engineered exosomes hold significant therapeutic potential for cancer treatment and immune modulation.