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ACS Nano, Jun 07 2024, | https://doi.org/10.1021/acsnano.4c02624 Unveiling the Power of Cloaking Metal-Organic Framework Platforms via Supramolecular Antibody Conjugation

Jun Yong Oh ¹, Batakrishna Jana ¹, Junmo Seong ¹, Eun-Koung An ², Eun Min Go ³, Seongeon Jin¹, Hae Won Ok ¹, Min-Seok Seu ¹, Jong-Hoon Bae ⁴, Chaiheon Lee ¹, Seonghwan Lee ¹, Tae-Hyuk Kwon ¹, Jeong Kon Seo ⁴, Eunshil Choi ¹, Jun-O Jin ², Sang Kyu Kwak ⁵, Myoung Soo Lah ¹, Ja-Hyoung Ryu ¹

¹Department of Chemistry, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.

²Department of Microbiology, University of Ulsan College of Medicine, Seoul 05505, South Korea.

³Department of Energy Engineering, School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.

⁴Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.

⁵Department of Chemical and Biological Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.

J.Y.O., B.J., and J.S. contributed equally.

Corresponding Authors : Sang Kyu Kwak, Myoung Soo Lah, Ja-Hyoung Ryu

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.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-18)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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