Protein-based drug delivery and thermal protection via Mof encapsulation

Conference Dates

November 10-14, 2019


Top: SEM images of TMV@ZIF a) non-stressed, b) heating at 100 °C for 20 min, and after soaking overnight in c) methanol, d) 6 M guanidinium chloride, and e) ethyl acetate. Scale bars represent 2 µm. f) TEM image of exfoliated non-stressed TMV. Scale bar is 200 nm. Bottom: The ELISA response of naked and encapsulated TMV subject to no stress (a), heating (b), methanol (c), 6 M guanidinium chloride (d), and ethyl acetate (e). The percentages range from buffer blank (0% TMV) to non-stressed naked TMV (100% TMV).

Recently, we and others have shown mechanistically how metal-organic frameworks (MOFs) are biomimetically formed on the surface of proteins and, once encapsulated, these bionanoparticles show dramatic enhanced thermal stability and resistance to denaturation in organic solvents. Earlier this year my colleagues and I presented a perspective (ACS Nano 2018, 1, 13–23) on a vision of how this nanotechnology could help “break the cold chain” with regards to vaccine delivery. Over the intervening months, we have come to realize we sold our vision short in this perspective—bionanomaterials formed via this method is capable of more. Specifically, as we report, ZIF-8 nano-structured proteins are near ideal candidates for controlled delivery of native proteins via subcutaneous implantation while protecting them in vivo against premature degradation. This would challenge the status quo for therapeutic protein delivery because vaccines are the largest market for therapeutic proteins in the world and they are one of the few medicines that are both shipped to places where 24-hour refrigeration is required yet not always available. Further, vaccines often require multiple administrations which means that a patient needs to return to a doctor. It has been suggested, however, that slow administration via time-release of vaccines may be a way to skip these multiple trips to the doctors. In developing nations, where infrastructure and trained medical professionals are scarce, this could be a lifesaving boon.

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