Cloaking Protein Shield Zr-MOF Delivery Platform for Targeted Nanomedicine

Abstract

Drug delivery systems in nanomedicine, involving various types of nanoparticles, can maximize therapeutic effects and enhance delivery efficacy. In particular, metal–organic frameworks (MOFs) have recently emerged as a promising delivery platform. Among the vast number of nanoscale MOFs, Zr-MOFs retain remarkable stability, and their biocompatible properties and functions make them one of the most favorable MOFs for nanomedicine. Despite the advantages of Zr-MOFs, nanomedical applications of their active sites, which are located on the surface, are still in an early stage. Indeed, naked MOFs lacking properly controlled active sites may react with immune proteins in a biological environment, causing loss of stability or removal by the immune system. In this study, we intended to advance the possibilities of a Zr-MOF-based delivery platform by utilizing self-assembling bonds between the MOF active site and various carboxyl groups in functional shield proteins. Functional cloaking proteins such as GST-Afb (HER2 and EGFR) are very stable, inhibit reactions with other proteins and can be used for targeting. Such proteins can stabilize the active site of the MOF and also act as a targeting moiety. We effectively controlled the MOF surface via an intrinsic reaction between the active site and recombinant proteins to develop a targeted drug delivery platform. This study provides an insight into the potential applications of Zr-MOFs in nanomedicine and the future of the biointerface of MOFs.