2023-10-30 カリフォルニア大学サンディエゴ校(UCSD)
◆この技術の利点は、同じモジュラーなナノ粒子ベースを使用して異なる専門用途のナノ粒子を簡単に作成できる点にあります。これにより、特定のアプリケーションに対して新たなナノ粒子を作成する手間が省けます。この技術は、がん治療やウイルスの無力化など、さまざまな生物学的アプリケーションに応用できます。
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遺伝子工学を用いた細胞膜被覆ナノ粒子の機能強化のためのモジュラーアプローチ A modular approach to enhancing cell membrane-coated nanoparticle functionality using genetic engineering
Nishta Krishnan,Yao Jiang,Jiarong Zhou,Animesh Mohapatra,Fei-Xing Peng,Yaou Duan,Maya Holay,Sanam Chekuri,Zhongyuan Guo,Weiwei Gao,Ronnie H. Fang & Liangfang Zhang
Nature Nanotechnology Published3:0 October 2023
DOI:https://doi.org/10.1038/s41565-023-01533-w
Abstract
Since their initial development, cell membrane-coated nanoparticles (CNPs) have become increasingly popular in the biomedical field. Despite their inherent versatility and ability to enable complex biological applications, there is considerable interest in augmenting the performance of CNPs through the introduction of additional functionalities. Here we demonstrate a genetic-engineering-based modular approach to CNP functionalization that can encompass a wide range of ligands onto the nanoparticle surface. The cell membrane coating is engineered to express a SpyCatcher membrane anchor that can readily form a covalent bond with any moiety modified with SpyTag. To demonstrate the broad utility of this technique, three unique targeted CNP formulations are generated using different classes of targeting ligands, including a designed ankyrin repeat protein, an affibody and a single-chain variable fragment. In vitro, the modified nanoparticles exhibit enhanced affinity towards cell lines overexpressing the cognate receptors for each ligand. When formulated with a chemotherapeutic payload, the modularly functionalized nanoparticles display strong targeting ability and growth suppression in a murine tumour xenograft model of ovarian cancer. Our data suggest genetic engineering offers a feasible approach for accelerating the development of multifunctional CNPs for a broad range of biomedical applications.
