Carrier gas triggered controlled biolistic delivery of DNA and protein therapeutics from metal–organic frameworks

Yalini H. Wijesundara, a   Fabian C. Herbert,a   Orikeda Trashi,a   Ikeda Trashi,a   Olivia R. Brohlin,a   Sneha Kumari, a   Thomas Howlett, a   Candace E. Benjamin, a   Arezoo Shahrivarkevishahi,a   Shashini D. Diwakara,a   Sachini D. Perera, a   Samuel A. Cornelius, c   Juan P. Vizuet, a   Kenneth J. Balkus, Jr,a   Ronald A. Smaldone, a   Nicole J. De Nisco c  and  Jeremiah J. Gassensmith *ab  

The efficacy and specificity of protein, DNA, and RNA-based drugs make them popular in the clinic; however, these drugs are often delivered via injection, requiring skilled medical personnel, and producing biohazardous waste. Here, we report an approach that allows for their controlled delivery, affording either a burst or slow release without altering the formulation. We show that when encapsulated within zeolitic-imidazolate framework eight (ZIF-8), the biomolecules are stable in powder formulations and can be inoculated with a low-cost, gas-powered “MOF-Jet” into living animal and plant tissues. Additionally, their release profiles can be modulated through judicious selection of the carrier gas used in the MOF-Jet. Our in vitro and in vivo studies reveal that when CO2 is used, it creates a transient and weakly acidic local environment that causes a near-instantaneous release of the biomolecules through an immediate dissolution of ZIF-8. Conversely, when air is used, ZIF-8 biodegrades slowly, releasing the biomolecules over a week. This is the first example of controlled-biolistic delivery of biomolecules using ZIF-8, which provides a powerful tool for fundamental and applied science research.

DOI:https://doi.org/10.1039/D2SC04982A


https://pubs.rsc.org/en/content/articlelanding/2022/sc/d2sc04982a


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