New Study Unveils the Power of Cloaking MOF Platforms via Supramolecular Antibody Conjugation

Abstract
Targeted drug delivery systems based on metal–organic frameworks (MOFs) have progressed tremendously since inception and are now widely applicable in diverse scientific fields. However, translating MOF agents directly to targeted drug delivery systems remains a challenge due to the biomolecular corona phenomenon. Here, we observed that supramolecular conjugation of antibodies to the surface of MOF particles (MOF-808) via electrostatic interactions and coordination bonding can reduce protein adhesion in biological environments and show stealth shields. Once antibodies are stably conjugated to particles, they were neither easily exchanged with nor covered by biomolecule proteins, which is indicative of the stealth effect. Moreover, upon conjugation of the MOF particle with specific targeted antibodies, namely, anti-CD44, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR), the resulting hybrid exhibits an augmented targeting efficacy toward cancer cells overexpressing these receptors, such as HeLa, SK-BR-3, and 4T1, as evidenced by flow cytometry. The therapeutic effectiveness of the antibody-conjugated MOF (anti-M808) was further evaluated through in vivo imaging and the assessment of tumor inhibition effects using IR-780-loaded EGFR-M808 in a 4T1 tumor xenograft model employing nude mice. This study therefore provides insight into the use of supramolecular antibody conjugation as a promising method for developing MOF-based drug delivery systems.

A research team, led by Professor Ja-Young Ryu from the Department of Chemistry at UNIST has developed a carrier that combines metal-organic framework (MOF) nanoparticles with antibodies. This innovative carrier can accurately target specific cancer cells. Antibody proteins are attached to the surface of MOF particles, enhancing bio-environmental safety by reducing unnecessary interactions with non-cancerous cells.

MOF nanoparticles are composed of metal clusters and organic structures. Various combinations can be formulated to create particles with diverse functionalities, including biocompatibility, heat sensitivity, and light sensitivity. However, immune cells can eliminate or aggregate the defects and reactive sites present on the particle surface.

Figure 1. Shown above is the cloaking antibody–MOF platform.

Addressing these challenges, the research team successfully conjugated antibody proteins to the MOF nanoparticles. This modification allows for precise identification of target cancer cells while minimizing unwanted reactions. The attachment of the antibody proteins does not induce significant chemical changes, thereby streamlining the process of complex formation.

The antibody-MOF complexes can target a wide variety of cancer cells. The antibody proteins serve as a protective layer, reducing adhesion to other proteins within the biological environment. Experimental results have demonstrated the efficacy of this complex.

Professor Ryu stated, “The method developed in this study has secured high versatility and stability as a drug carrier by attaching actual antibody proteins to MOF nanoparticles.”

The findings of this research have been published in ACS Nano on June 7, 2024. The research was conducted in collaboration with Professor Myoung Soo Lah in the Department of Chemistry at UNIST and Professor Sang Kyu Kwak from Korea University, and it received support from the National Research Foundation of Korea (NRF) under the Ministry of Science and ICT (MSIT).

Journal Reference
Jun Yong Oh, Batakrishna Jana, Junmo Seong, et al., “Unveiling the Power of Cloaking Metal–Organic Framework Platforms via Supramolecular Antibody ConjugationArticle link copied!,” ACS Nano, (2024).