학술논문
Glucosylation endows nanoparticles with TLR4 agonist capability to trigger macrophage polarization and augment antitumor immunity.
Document Type
Academic Journal
Author
Liu L; Institute of Respiratory Health, West China Hospital, Sichuan University, Chengdu, 610041, PR China; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, PR China.; Fu S; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, PR China; Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, PR China.; Zhu W; Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, PR China.; Cai Z; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, PR China.; Cao Y; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, PR China.; Huang Y; School of Medicine, School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, 510006, PR China.; Yang L; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, PR China.; Fu X; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, PR China.; Jin R; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, PR China.; Xia C; Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, PR China.; Zhang Y; School of Medicine, School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, 510006, PR China.; Lui S; Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, PR China.; Gong Q; Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, PR China.; Song B; Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, PR China.; Wen L; School of Medicine, School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, 510006, PR China.; Anderson JM; Department of Pathology, Case Western Reserve University, Cleveland, OH, 44106, USA; Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.; Ai H; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, PR China; Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, PR China. Electronic address: huaai@scu.edu.cn.
Source
Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8100316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5905 (Electronic) Linking ISSN: 01429612 NLM ISO Abbreviation: Biomaterials Subsets: MEDLINE
Subject
Language
English
Abstract
Carbohydrates have emerged as promising candidates for immunomodulation, however, how to present them to immune cells and achieve potent immunostimulatory efficacy remains challenging. Here, we proposed and established an effective way of designing unique glyconanoparticles that can amplify macrophage-mediated immune responses through structural mimicry and multiple stimulation. We demonstrate that surface modification with glucose can greatly augment the immunostimulatory efficacy of nanoparticles, comparing to mannose and galactose. In vitro studies show that glucosylation improved the pro-inflammatory efficacy of iron oxide nanoparticles (IONPs) by up to 300-fold, with the immunostimulatory activity of glucosylated IONPs even surpassing that of LPS under certain conditions. In vivo investigation show that glucosylated IONPs elicited increased antitumor immunity and achieved favorable therapeutic outcomes in multiple murine tumor models. Mechanistically, we proposed that glucosylation potentiated the immunostimulatory effect of IONPs by amplifying toll-like receptors 4 (TLR4) activation. Specifically, glucosylated IONPs directly interacted with the TLR4-MD2 complex, resulting in M1 macrophage polarization and enhanced antitumor immunity via activation of NF-κB, MAPK, and STAT1 signaling pathways. Our work provides a simple modification strategy to endow nanoparticles with potent TLR4 agonist effects, which may shed new light on the development of artificial immune modulators for cancer immunotherapy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)