Endocytosis-Like Vesicle Fission Mediated by a Membrane-Expanding Molecular Machine Enables Virus Encapsulation for In Vivo Delivery,Journal of the American Chemical Society

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Endocytosis-Like Vesicle Fission Mediated by a Membrane-Expanding Molecular Machine Enables Virus Encapsulation for In Vivo Delivery
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2023-02-28 , DOI: 10.1021/jacs.2c12348
Noriyuki Uchida ₁ , Yunosuke Ryu ₁ , Yuichiro Takagi ₁ , Ken Yoshizawa ₁ , Kotono Suzuki ₁ , Yasutaka Anraku ₂ , Itsuki Ajioka _{3,

4} , Naofumi Shimokawa ₅ , Masahiro Takagi ₅ , Norihisa Hoshino ₆ , Tomoyuki Akutagawa ₆ , Teruhiko Matsubara ₇ , Toshinori Sato ₇ , Yuji Higuchi ₈ , Hiroaki Ito ₉ , Masamune Morita ₁₀ , Takahiro Muraoka _{1,

4,

11}

Affiliation

Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Center for Brain Integration Research Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Kanagawa Institute of Industrial Science and Technology, 705-1 Shimoimaizumi, Ebina, Kanagawa 243-0435, Japan.
School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan.
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kouhoku-ku, Yokohama, Kanagawa 223-8522, Japan.
Institute for Solid State Physics, The University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba 277-8581, Japan.
Department of Physics, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
National Institute of Advanced Industrial Science and Technology, Center 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 3-8-1 Harumi-cho, Fuchu, Tokyo 183-8538, Japan.

Biological membranes are functionalized by membrane-associated protein machinery. Membrane-associated transport processes, such as endocytosis, represent a fundamental and universal function mediated by membrane-deforming protein machines, by which small biomolecules and even micrometer-size substances can be transported via encapsulation into membrane vesicles. Although synthetic molecules that induce dynamic membrane deformation have been reported, a molecular approach enabling membrane transport in which membrane deformation is coupled with substance binding and transport remains critically lacking. Here, we developed an amphiphilic molecular machine containing a photoresponsive diazocine core (AzoMEx) that localizes in a phospholipid membrane. Upon photoirradiation, AzoMEx expands the liposomal membrane to bias vesicles toward outside-in fission in the membrane deformation process. Cargo components, including micrometer-size M13 bacteriophages that interact with AzoMEx, are efficiently incorporated into the vesicles through the outside-in fission. Encapsulated M13 bacteriophages are transiently protected from the external environment and therefore retain biological activity during distribution throughout the body via the blood following administration. This research developed a molecular approach using synthetic molecular machinery for membrane functionalization to transport micrometer-size substances and objects via vesicle encapsulation. The molecular design demonstrated in this study to expand the membrane for deformation and binding to a cargo component can lead to the development of drug delivery materials and chemical tools for controlling cellular activities.

中文翻译：

由膜扩张分子机器介导的内吞作用样囊泡裂变使病毒封装用于体内递送

生物膜由膜相关蛋白机制功能化。膜相关运输过程，如内吞作用，代表了由膜变形蛋白机器介导的基本和普遍功能，小生物分子甚至微米大小的物质可以通过封装进入膜囊泡。尽管已经报道了诱导动态膜变形的合成分子，但仍然严重缺乏一种使膜变形与物质结合和运输相结合的膜运输分子方法。在这里，我们开发了一种两亲分子机器，其中包含位于磷脂膜中的光敏重氮辛核 (AzoMEx)。光照射后，AzoMEx 扩张脂质体膜，使囊泡在膜变形过程中偏向由外向内裂变。货物成分，包括与 AzoMEx 相互作用的微米大小的 M13 噬菌体，通过由外向内裂变有效地掺入囊泡中。封装的 M13 噬菌体暂时受到外部环境的保护，因此在给药后通过血液分布到全身期间保持生物活性。这项研究开发了一种分子方法，使用合成分子机制进行膜功能化，通过囊泡封装运输微米级物质和物体。

更新日期：2023-02-28

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