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

• Published in: Chemistry of materials 2022-09, Vol.34 (17), p.7817-7827
• Main Authors: Cases Díaz, Jesús, Lozano-Torres, Beatriz, Giménez-Marqués, Mónica
• Format: Article
• Language: English
• ISSN: 0897-4756; 1520-5002
• DOI: 10.1021/acs.chemmater.2c01338

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.