<br>通过超分子抗体缀合揭示隐藏金属有机框架平台的力量,ACS Nano

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通过超分子抗体缀合揭示隐藏金属有机框架平台的力量
ACS Nano ( IF 15.8 ) Pub Date : 2024-06-07 , DOI: 10.1021/acsnano.4c02624
Jun Yong Oh ₁ , Batakrishna Jana ₁ , Junmo Seong ₁ , Eun-Koung An ₂ , Eun Min Go ₃ , Seongeon Jin ₁ , 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

Affiliation

基于金属有机框架（MOF）的靶向药物递送系统自诞生以来已经取得了巨大进步，现已广泛应用于不同的科学领域。然而，由于生物分子电晕现象，将 MOF 试剂直接转化为靶向药物递送系统仍然是一个挑战。在这里，我们观察到抗体通过静电相互作用和配位键与 MOF 颗粒（MOF-808）表面的超分子缀合可以减少生物环境中的蛋白质粘附并显示出隐形屏蔽。一旦抗体与颗粒稳定结合，它们既不容易与生物分子蛋白交换，也不会被生物分子蛋白覆盖，这表明了隐形效应。此外，将 MOF 颗粒与特异性靶向抗体（即抗 CD44、人表皮生长因子受体 2 (HER2) 和表皮生长因子受体 (EGFR)）结合后，所得杂合体对过度表达的癌细胞表现出增强的靶向功效。流式细胞术证实了这些受体，例如 HeLa、SK-BR-3 和 4T1。通过体内成像和使用负载 IR-780 的 EGFR-M808 在裸鼠 4T1 肿瘤异种移植模型中评估肿瘤抑制效果，进一步评估了抗体缀合的 MOF（抗 M808）的治疗效果。因此，这项研究提供了关于使用超分子抗体缀合作为开发基于 MOF 的药物递送系统的有前途的方法的见解。

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Unveiling the Power of Cloaking Metal–Organic Framework Platforms via Supramolecular Antibody Conjugation

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.

更新日期：2024-06-07

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