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Computer-Aided Design of Self-Assembled Nanoparticles to Enhance Cancer Chemoimmunotherapy via Dual-Modulation Strategy

文献类型：期刊论文

作者Shan, Xiaoting4,5,6; Cai, Ying3,4,5,6; Zhu, Binyu4,5,6; Sun, Xujie4,5,6; Zhou, Lingli5,6; Zhao, Zhiwen4,5,6; Li, Yaping2,3,4,5,6; Wang, Dangge1
刊名ADVANCED HEALTHCARE MATERIALS
出版日期2025-01-19
页码15
关键词cancer chemoimmunotherapy computer-aided design nanoparticles pharmacophore hybridization triple-negative breast cancer
ISSN号2192-2640
DOI10.1002/adhm.202404261
英文摘要The rational design of self-assembled compounds is crucial for the highly efficient development of carrier-free nanomedicines. Herein, based on computer-aided strategies, important physicochemical properties are identified to guide the rational design of self-assembled compounds. Then, the pharmacophore hybridization strategy is used to design self-assemble nanoparticles by preparing new chemical structures by combining pharmacophore groups of different bioactive compounds. Hydroxychloroquine is grafted with the lipophilic vitamin E succinate and then co-assembled with bortezomib to fabricate the nanoparticle. The nanoparticle can reduce M2-type tumor-associated macrophages (TAMs) through lysosomal alkalization and induce immunogenic cell death (ICD) and nuclear factor-kappa B (NF-kappa B) inhibition in tumor cells. In mouse models, the nanoparticles induce decreased levels of M2-type TAMs, regulatory T cells, and transforming growth factor-beta (TGF-beta), and increase the proportion of cytotoxicity T lymphocytes. Additionally, the nanoparticles reduce the secretion of Interleukin-6 (IL-6) by inhibiting NF-kappa B and enhance the programmed death ligand-1 (PD-L1) checkpoint blockade therapy. The pharmacophore hybridization-derived nanoparticle provides a dual-modulation strategy to reprogram the tumor microenvironment, which will efficiently enhance the chemoimmunotherapy against triple-negative breast cancer.
WOS关键词TUMOR-ASSOCIATED MACROPHAGES ; RESISTANCE
资助项目National Natural Science Foundation of China ; Shanghai Advanced Research Institute, Chinese Academy of Sciences, China ; Shanghai Rising-star Program[23QA1411200] ; [32170935] ; [32130058]
WOS研究方向Engineering ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:001398705600001
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/315908]  
专题新药研究国家重点实验室
通讯作者Li, Yaping; Wang, Dangge
作者单位1.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Precis Res Ctr Refractory Dis, Sch Med, Shanghai 201620, Peoples R China
2.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264000, Peoples R China
3.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Shandong, Peoples R China
4.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Shan, Xiaoting,Cai, Ying,Zhu, Binyu,et al. Computer-Aided Design of Self-Assembled Nanoparticles to Enhance Cancer Chemoimmunotherapy via Dual-Modulation Strategy[J]. ADVANCED HEALTHCARE MATERIALS,2025:15.
APA Shan, Xiaoting.,Cai, Ying.,Zhu, Binyu.,Sun, Xujie.,Zhou, Lingli.,...&Wang, Dangge.(2025).Computer-Aided Design of Self-Assembled Nanoparticles to Enhance Cancer Chemoimmunotherapy via Dual-Modulation Strategy.ADVANCED HEALTHCARE MATERIALS,15.
MLA Shan, Xiaoting,et al."Computer-Aided Design of Self-Assembled Nanoparticles to Enhance Cancer Chemoimmunotherapy via Dual-Modulation Strategy".ADVANCED HEALTHCARE MATERIALS (2025):15.

入库方式： OAI收割

来源：上海药物研究所

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