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Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells

文献类型：期刊论文

作者Sun, Xiangshi1; Xu, Xiaoxuan2,3; Wang, Jue2,3; Zhang, Xinyue7; Zhao, Zitong2,3; Liu, Xiaochen2,3; Wang, Guanru2,3; Teng, Lesheng5; Chen, Xia1; Wang, Dangge2,3,4
刊名ACTA PHARMACEUTICA SINICA B
出版日期2023-07-01
卷号13期号:7页码:3093-3105
ISSN号2211-3835
关键词Nanoparticle Aggregation Drug retention Natural killer cells Cancer immunotherapy Acid-switchable Galunisertib IL-15
DOI10.1016/j.apsb.2023.02.002
通讯作者Chen, Xia(chenxjluedu@163.com) ; Wang, Dangge(dgwang@simm.ac.cn) ; Li, Yaping(ypli@simm.ac.cn)
英文摘要Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active recep-tors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8 thorn T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells. 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
WOS关键词NK CELL ; INTERLEUKIN-15 ; CHECKPOINT ; THERAPY ; BETA
资助项目National Natural Science Foundation of China[32170935] ; National Natural Science Foundation of China[81903548] ; National Natural Science Foundation of China[31930066] ; Youth Innovation Promotion Association of CAS[2019283] ; Shandong Provincial Natural Science Foundation[ZR2019PH013]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
WOS记录号WOS:001045891200001
源URL[http://119.78.100.183/handle/2S10ELR8/306896]  
专题新药研究国家重点实验室
通讯作者Chen, Xia; Wang, Dangge; Li, Yaping
作者单位1.Jilin Univ, Coll Basic Med Sci, Dept Pharmacol, Changchun 130021, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
4.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Peoples R China
5.Jilin Univ, Sch Life Sci, Changchun 130012, Peoples R China
6.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264000, Peoples R China
7.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
推荐引用方式
GB/T 7714		 Sun, Xiangshi,Xu, Xiaoxuan,Wang, Jue,et al. Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells[J]. ACTA PHARMACEUTICA SINICA B,2023,13(7):3093-3105.
APA Sun, Xiangshi.,Xu, Xiaoxuan.,Wang, Jue.,Zhang, Xinyue.,Zhao, Zitong.,...&Li, Yaping.(2023).Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells.ACTA PHARMACEUTICA SINICA B,13(7),3093-3105.
MLA Sun, Xiangshi,et al."Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells".ACTA PHARMACEUTICA SINICA B 13.7(2023):3093-3105.

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来源：上海药物研究所

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