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

Encapsulation of biomolecules using metal-organic frame-works (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.

Automated summary

This study presents a method for encapsulating biomolecules using metal-organic frameworks (MOFs) and demonstrates that MOFs based on cations with acidity can encapsulate proteins with different surface properties. The research shows that this encapsulation method can release proteins under biocompatible conditions and maintain their activity in denaturing environments. Additionally, the study finds that myoglobin-carrying biocomposites can overcome chemoresistance caused by hypoxia.