机构：[1]Department of Neurosurgery and Institute of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.四川大学华西医院[2]Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P. R. China.[3]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P. R. China.四川大学华西医院
Administration of bispecific antibodies (biAbs) in tumor therapy is limited by their short half-life and off-target toxicity. Optimized strategies or targets are needed to overcome these barriers. B7-H3 (CD276), a member of the B7 superfamily, is associated with poor survival in glioblastoma (GBM) patients. Moreover, a dimer of EGCG (dEGCG) synthesized in this work enhanced the IFN-γ-induced ferroptosis of tumor cells in vitro and in vivo. Herein, we prepared recombinant anti-B7-H3×CD3 biAbs and constructed MMP-2-sensitive S-biAb/dEGCG@NPs to offer a combination treatment strategy for efficient and systemic GBM elimination. Given their GBM targeted delivery and tumor microenvironment responsiveness, S-biAb/dEGCG@NPs displayed enhanced intracranial accumulation, 4.1-, 9.5-, and 12.3-fold higher than that of biAb/dEGCG@NPs, biAb/dEGCG complexes, and free biAbs, respectively. Furthermore, 50% of GBM-bearing mice in the S-biAb/dEGCG@NP group survived longer than 56 days. Overall, S-biAb/dEGCG@NPs can induce GBM elimination by boosting the ferroptosis effect and enhancing immune checkpoint blockade (ICB) immunotherapy and may be successful antibody nanocarriers for enhanced cancer therapy.
基金：
This work was financially supported by the National Natural
Science Foundation of China (Grants 82102767 and
82002638), the Fundamental Research Funds for the Central
Universities, the Postdoctoral Foundation of Sichuan University
(Grant 2020SCU12037), 1·3·5 Project for Disciplines
of ExcellenceClinical Research Incubation Project, West
China Hospital, Sichuan University (Grant 2020HXFH036),
and the Knowledge Innovation Program of the Chinese
Academy of Sciences (Grant JH2022007).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|1 区材料科学
小类|1 区化学：综合1 区物理化学1 区材料科学：综合1 区纳米科技
最新[2023]版：
大类|1 区材料科学
小类|1 区化学：综合1 区物理化学1 区材料科学：综合1 区纳米科技
第一作者：
第一作者机构：[1]Department of Neurosurgery and Institute of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.
通讯作者：
通讯机构：[1]Department of Neurosurgery and Institute of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.[3]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P. R. China.[*1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P. R. China[*2]Department of Neurosurgery and Institute of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China
推荐引用方式(GB/T 7714)：
Fan Rangrang,Chen Caili,Mu Min,et al.Engineering MMP-2 Activated Nanoparticles Carrying B7-H3 Bispecific Antibodies for Ferroptosis-Enhanced Glioblastoma Immunotherapy[J].ACS nano.2023,doi:10.1021/acsnano.2c12217.
APA：
Fan Rangrang,Chen Caili,Mu Min,Chuan Di,Liu Hao...&Xu Jianguo.(2023).Engineering MMP-2 Activated Nanoparticles Carrying B7-H3 Bispecific Antibodies for Ferroptosis-Enhanced Glioblastoma Immunotherapy.ACS nano,,
MLA：
Fan Rangrang,et al."Engineering MMP-2 Activated Nanoparticles Carrying B7-H3 Bispecific Antibodies for Ferroptosis-Enhanced Glioblastoma Immunotherapy".ACS nano .(2023)
材料科学