Metal-organic framework as a new antibody-drug delivery system

Significance 

To enhance  the  targeting properties of Ab, the protein should ideally be positioned with the fragment crystallizable (Fc) region oriented  toward  the  nanoparticle  surface,  thereby  leaving  the  fragment  antigen-binding  (Fab) regions free to target specific antigens. A precise and homogeneous Ab orientation would greatly reduces nonspecific tissue  interactions  and  off-target  effects  in  vivo. However,  precise  Ab orientation on particles is made cumbersome by employing chemical protocols (e.g. protein fusion methods) or is limited to specific materials (e.g. gold). Thus, new facile and versatile Ab-directed chemistries will facilitate the use of Ab-targeted particles in modern medicine.

The metal-organic framework, a mixture of metal (zinc) and carbonate ions, and a small organic molecule (an imidazole, a colorless solid compound that is soluble in water) not only keeps the payload attached to the antibody but can also acts as a reservoir of personalized therapeutics. This is a benefit with the potential to become a new medical tool to target specific diseases with customized drugs and optimized doses.

The research was led by Professor Christoph Hagemeyer, Head of the NanoBiotechnology Laboratory at the Australian Centre for Blood Diseases, Monash University.  The findings are now published in the journal Advanced Materials. The new method is cheaper, faster and more versatile than anything available currently.  The method offers the opportunity to personalize treatment and given the precision possible, may eventually change the current dosage needed for patients, resulting in fewer side effects and making treatments cheaper. The authors proposed that the anisotropy of both the shape and surface chemistry of Abs could trigger a spatially controlled crystallization of a Zn-based ZIF predominantly around the Fc region and, thus, afford orientation-controlled insertion of Abs in MOF particles

The in vitro study showed that when MOF antibody crystals bind to their target cancer cells and if exposed to the low pH in the cells, they break down, delivering the drugs directly and solely to the desired area.

Metal-organic framework as a new antibody-drug delivery system - Medicine Innovates

About the author

Professor Christoph Hagemeyer, a chemist by training, obtained a PhD in Biochemistry from the University of Freiburg (Germany). He made contributions to the field of Cytochrome P450 metabolism in the rodent brain before moving into cardiovascular research developing anti-thrombotic recombinant fusion proteins and novel imaging probes. He migrated to Australia in 2005 and is currently Head of the NanoBiotechnology Laboratory at Monash University’s Australian Centre for Blood Diseases. His main research interests are drug delivery, molecular imaging and novel bioconjugation techniques in thrombosis, inflammation and cancer.

Reference

Karen Alt , Francesco Carraro , Edwina Jap , Mercedes Linares-Moreau , Raffaele Riccò , Marcello Righetto , Marco Bogar , Heinz Amenitsch , Rania A Hashad, Christian Doonan , Christoph E Hagemeyer , Paolo Falcaro . Self-Assembly of Oriented Antibody-Decorated Metal-Organic Framework Nanocrystals for Active Targeting Applications. Adv Mater. 2021 Dec 6;e2106607. doi: 10.1002/adma.202106607.

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