Forming next-generation antibody-nanoparticle conjugates through the oriented installation of non-engineered antibody fragments.
Forming next-generation antibody-nanoparticle conjugates through the oriented installation of non-engineered antibody fragments.
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通过非工程抗体片段的定向安装形成下一代抗体-纳米颗粒缀合物。
DOI：
10.1039/c7sc02747h
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发表时间：
2018-01-07
期刊：
影响因子：
8.4
通讯作者：
Chudasama V
中科院分区：
文献类型：
--
作者：
Greene MK;Richards DA;Nogueira JCF;Campbell K;Smyth P;Fernández M;Scott CJ;Chudasama V
使非工程抗体片段能够定向安装在纳米颗粒表面上，以产生下一代抗体-纳米颗粒缀合物。靶向纳米治疗剂的成功开发取决于治疗性纳米颗粒与靶特异性配体的缀合，特别强调基于抗体的配体。因此，非常需要能够将靶向抗体共价且精确地安装到纳米颗粒表面的新方法，特别是不依赖于昂贵且耗时的抗体工程技术的那些方法。本文中，我们提出了一种使用二硫键选择性哒嗪二酮接头和应变促进的炔-叠氮化物点击化学将非工程化抗体F（ab）片段高度受控和定向共价缀合至PLGA-PEG纳米颗粒的新方法。当与常用的抗体-纳米颗粒构建策略相比时，用曲妥珠单抗和西妥昔单抗的这种方法的示例显示出缀合效率和抗原结合能力的显著改善。这种新方法为开发抗体靶向纳米药物铺平了道路，具有改进的互补位可用性，重现性和均匀性，以提高生物活性和易于制造。
Enabling oriented installation of non-engineered antibody fragments on nanoparticle surfaces to create next-generation antibody–nanoparticle conjugates. The successful development of targeted nanotherapeutics is contingent upon the conjugation of therapeutic nanoparticles to target-specific ligands, with particular emphasis being placed on antibody-based ligands. Thus, new methods that enable the covalent and precise installation of targeting antibodies to nanoparticle surfaces are greatly desired, especially those which do not rely on costly and time-consuming antibody engineering techniques. Herein we present a novel method for the highly controlled and oriented covalent conjugation of non-engineered antibody F(ab) fragments to PLGA–PEG nanoparticles using disulfide-selective pyridazinedione linkers and strain-promoted alkyne–azide click chemistry. Exemplification of this method with trastuzumab and cetuximab showed significant improvements in both conjugation efficiency and antigen binding capability, when compared to commonly employed strategies for antibody–nanoparticle construction. This new approach paves the way for the development of antibody-targeted nanomedicines with improved paratope availability, reproducibility and uniformity to enhance both biological activity and ease of manufacture.
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影响因子：
8.4
作者：
Lee MTW;Maruani A;Richards DA;Baker JR;Caddick S;Chudasama V
通讯作者：
Chudasama V
影响因子：
6.2
作者：
Anderson, George P.;Glaven, Richard H.;Goldman, Ellen R.
通讯作者：
Goldman, Ellen R.
DOI：
10.1038/mt.2015.175
发表时间：
2016-02
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
Katakowski JA;Mukherjee G;Wilner SE;Maier KE;Harrison MT;DiLorenzo TP;Levy M;Palliser D
通讯作者：
Palliser D
影响因子：
13.3
作者：
Elias, Drew R.;Cheng, Zhiliang;Tsourkas, Andrew
通讯作者：
Tsourkas, Andrew
影响因子：
6.7
作者：
Jeong, Sinyoung;Park, Ji Yong;Jeong, Dae Hong
通讯作者：
Jeong, Dae Hong