Boosting Protein Encapsulation through Lewis-Acid-Mediated Metal-Organic Framework Mineralization: Toward Effective Intracellular Delivery

Chem Mater. 2022 Sep 13;34(17):7817-7827. doi: 10.1021/acs.chemmater.2c01338. Epub 2022 Aug 29.

ABSTRACT

Encapsulation of biomolecules using metal-organic frameworks (MOFs) to form stable biocomposites has been demonstrated to be a valuable strategy for their preservation and controlled release, which has been however restricted to specific electrostatic surface conditions. We present a Lewis-acid-mediated general in situ strategy that promotes the spontaneous MOF growth on a broad variety of proteins, for the first time, regardless of their surface nature. We demonstrate that MOFs based on cations exhibiting considerable inherent acidity such as MIL-100(Fe) enable efficient biomolecule encapsulation, including elusive alkaline proteins previously inaccessible by the well-developed in situ azolate-based MOF encapsulation. Specifically, we prove the MIL-100(Fe) scaffold for the encapsulation of a group of proteins exhibiting very different isoelectric points (5 < pI < 11), allowing triggered release under biocompatible conditions and retaining their activity after exposure to denaturing environments. Finally, we demonstrate the potential of the myoglobin-carrying biocomposite to facilitate the delivery of O2 into hypoxic human lung carcinoma A549 cells, overcoming hypoxia-associated chemoresistance.

PMID:36117882 | PMC:PMC9476658 | DOI:10.1021/acs.chemmater.2c01338

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