Exosomes-nanosized extracellular vesicles (EVs) naturally secreted from cells-have emerged as promising biomarkers and potential therapeutic vehicles, but methods to manipulate them for engineering purposes remain elusive. Among the technical obstacles are the small size and surface complexity of exosomes and the complex processing steps required, which reduce the biocompatibility of currently available methods. The encapsulation of exosomes with a nanofilm of supramolecular complexes of ferric ions (Fe3+ ) and tannic acid is demonstrated here. The resulting natural polyphenol, ≈10 nm thick, protects exosomes from external aggressors such as UV-C irradiation or heat and is controllably degraded on demand. Furthermore, gold nanoparticles can be covalently attached for single-exosome level visualization. To fully exploit their therapeutic potential, chemotherapeutic drug-loaded EVs are functionalized to achieve the targeted, selective killing of cancer cells preferentially over normal cells. This nanofilm not only preserves the native size and chemical makeup of the intrinsic exosomes, but also confers new capabilities for efficient tumor targeting and pH-controlled release of drugs. Demonstrating a scalable method to produce biocompatible, durable, on-demand degradable, and chemically controllable shields for exosome modification and functionalization, the methods introduced here are expected to bring the potential of exosome-based nanomedicine applications closer to reality.
Keywords: exosomes; nanoencapsulation; nanofilms; surface engineering; tannic acid.
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