【公開日：2023.07.31】【最終更新日：2023.05.16】
課題データ / Project Data
課題番号 / Project Issue Number
22UT0029
利用課題名 / Title
ガン治療のためのドラックデリバリーシステムの開発
利用した実施機関 / Support Institute
東京大学 / Tokyo Univ.
機関外・機関内の利用 / External or Internal Use
内部利用（ARIM事業参画者以外）/Internal Use (by non ARIM members)
技術領域 / Technology Area
【横断技術領域 / Cross-Technology Area】（主 / Main）計測・分析/Advanced Characterization（副 / Sub）-
【重要技術領域 / Important Technology Area】（主 / Main）次世代バイオマテリアル/Next-generation biomaterials（副 / Sub）-
キーワード / Keywords
電子顕微鏡/Electron microscopy,DDSマテリアル/ DDS material
利用者と利用形態 / User and Support Type
利用者名（課題申請者）/ User Name (Project Applicant)
HONG Taehun
所属名 / Affiliation
東京大学
共同利用者氏名 / Names of Collaborators in Other Institutes Than Hub and Spoke Institutes
CHEN Pengwen,Wenqian YANG
ARIM実施機関支援担当者 / Names of Collaborators in The Hub and Spoke Institutes
Ayumi Kimura
利用形態 / Support Type
（主 / Main）機器利用/Equipment Utilization（副 / Sub）,技術補助/Technical Assistance
利用した主な設備 / Equipment Used in This Project
UT-011：有機材料ハイコントラスト透過型電子顕微鏡
UT-010：クライオ透過型/透過走査型電子顕微鏡
報告書データ / Report
概要（目的・用途・実施内容）/ Abstract (Aim, Use Applications and Contents)
We developed a drug delivery system that specifically targets cancer cells in the body, in order to achieve effective cancer treatment with minimal side effects. Our approach involves delivering drugs that would normally have little effect when simply injected into the body, by encapsulating them in high-biocompatibility polymers that can precisely target cancer cells. For example, we have developed mechanisms to package messenger RNA (mRNA) or antibody proteins into these polymers, in a way that ensures they are delivered to the right place, and release drugs at the right time to have the desired effect. In order to precisely target drugs to specific tissues that are shielded by a variety of biological filters within the body, it is important to carefully control the size and hardness of the drug particles. In our research, we used transmission electron microscopes (JEM-1400 and JEM-2100F) to investigate the size and hardness of the drug particles we manipulated, and to evaluate whether they accurately pass through the intricate microstructures inside cells.
実験 / Experimental
We developed pH-responsive mRNA micelles aimed at escaping from endosomes. To ensure that the micelles only open within endosomes and not in other locations in the body, they needed to be rigid. We attempted to create micelles harder than conventional ones by cross-linking CAA onto PEG-PLys commonly used in micelle production. And then, the rigidity was compared by estimating the staining patterns of uranium between CAA micelles and PEG-Plys micelles. Next, we created antibody-encapsulated micelles for use in immunotherapy. We determined whether the particles were enclosed within the PEG shell by comparing the overall size measured by DLS with the core size measured by JEM-1400. Finally, we developed a system that accurately targets mitochondria to treat cancer. We confirmed the accurate delivery of drug particles to the mitochondria and their local distribution in 3D images using JEM-2100.
結果と考察 / Results and Discussion
We have developed micelles that release mRNA in response to pH. In addition to measuring their formation and particle size, we investigated whether they exist stably in tissues other than cancer by comparing their hardness using TEM.pH responsible micelles showed different uran staining patters depending on pH. Similarly, we developed micelles that release antibodies in response to pH and examined the thickness of their core and outer shell using TEM.The shell and core size of the micelles were analyzed by comparing TEM image and DLS data. Micelles made with longer PEG showed thicker shells. Finally, we developed nanocarriers that target mitochondria and verified their local distribution in 3D using cryo-TEM tomography.The mitochondrial targeting nanocarriers were accumulated at the matrix of mitochodnria.
図・表・数式 / Figures, Tables and Equations
その他・特記事項（参考文献・謝辞等） / Remarks(References and Acknowledgements)
成果発表・成果利用 / Publication and Patents
論文・プロシーディング（DOIのあるもの） / DOI (Publication and Proceedings)
-
Pengwen Chen, Nanocarriers escaping from hyperacidified endo/lysosomes in cancer cells allow tumor-targeted intracellular delivery of antibodies to therapeutically inhibit c-MYC, Biomaterials, 288, 121748(2022).
DOI: 10.1016/j.biomaterials.2022.121748
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Wenqian Yang, Polymeric Micelles with pH-Responsive Cross-Linked Core Enhance In Vivo mRNA Delivery, Pharmaceutics, 14, 1205(2022).
DOI: 10.3390/pharmaceutics14061205
口頭発表、ポスター発表および、その他の論文 / Oral Presentations etc.
特許 / Patents
特許出願件数 / Number of Patent Applications：0件
特許登録件数 / Number of Registered Patents：0件