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A novel HER2 targeting nanoagent self-assembled from affibody-epothilone B conjugate for cancer therapy.
Xia, Xuelin; Yang, Xiaoyuan; Gao, Wenhui; Huang, Wei; Xia, Xiaoxia; Yan, Deyue.
Afiliación
  • Xia X; School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.
  • Yang X; School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.
  • Gao W; School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.
  • Huang W; School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.
  • Xia X; State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China. xiaoxiaxia@sjtu.edu.cn.
  • Yan D; School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China. dyyan@sjtu.edu.cn.
J Nanobiotechnology ; 22(1): 502, 2024 Aug 21.
Article en En | MEDLINE | ID: mdl-39169343
ABSTRACT
Epothilone B (Epo B), a promising antitumor compound effective against various types of cancer cells in vitro. However, its poor selectivity for tumor cells and inadequate therapeutic windows significantly limit its potential clinical application. Affibody is a class of non-immunoglobulin affinity proteins with precise targeting capability to overexpressed molecular receptors on cancer cells, has been intensively investigated due to its exceptional affinity properties. In this study, we present a targeted nanoagent self-assembled from the precursor of an affibody conjugated with Epo B via a linker containing the thioketal (tk) group that is sensitive to reactive oxygen species (ROS). The core-shell structure of the ZHER2342-Epo B Affibody-Drug Conjugate Nanoagent (Z-E ADCN), with the cytotoxin Epo B encapsulated within the ZHER2342 affibody corona, leads to significantly reduced side effects on normal organs. Moreover, the abundant presence of ZHER2342 on the surface effectively enhances the targeting capacity and tumor accumulation of the drug. Z-E ADCN can be internalized by cancer cells via HER2 receptor-mediated endocytosis followed by Epo B release in response to high levels of ROS, resulting in excellent anticancer efficacy in HER2-positive tumor models.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Recombinantes de Fusión / Receptor ErbB-2 / Epotilonas Límite: Animals / Female / Humans Idioma: En Revista: J Nanobiotechnology Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Recombinantes de Fusión / Receptor ErbB-2 / Epotilonas Límite: Animals / Female / Humans Idioma: En Revista: J Nanobiotechnology Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido