Multimodal enzyme delivery and therapy enabled by cell membrane-coated metal-organic framework nanoparticles
Enzymes for the treatment of genetic or metabolic diseases often suffer from poor pharmacokinetics and stability, and nanodrug delivery systems are expected to improve the performance of enzyme therapies. UC San Diego Zhang Liangfang/Ronnie H. Fang developed a cell membrane camouflaged metal-organic framework (MOF) system with enhanced biocompatibility and functionality. The MOF core can efficiently encapsulate enzymes while maintaining their biological activity. The biocompatibility of the formulations can be improved after the introduction of natural cell membrane modifications. Surface receptors on membranes can also provide other functions that synergize with encapsulated enzymes, enabling disease-targeted drug delivery. Using uricase as a model enzyme, the authors demonstrate the efficacy of this approach in a variety of animal disease models.
The authors successfully fabricated a cell membrane-coated MOF platform to enhance the activity of enzyme therapy. Using uricase as a model enzyme, the high encapsulation efficiency of this enzyme was demonstrated, and the biofilm modification further improved the colloidal stability of the formulation. Importantly, the formulation retains the activity of the enzyme, which can protect the encapsulated enzyme from degradation. Demonstrating the versatility of this approach, two independent systems were developed using membranes derived from erythrocytes or macrophages. Erythrocyte membrane-coated MOF-uricase preparations can be used for systemic treatment of hyperuricemia, rapidly reducing serum uric acid levels. On the other hand, macrophage membranes, which have the ability to neutralize various pro-inflammatory cytokines, act synergistically with uricase to effectively treat local joint inflammation caused by the deposition of insoluble uric acid.
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