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Perfluorocarbon loaded fluorinated covalent organic polymers with effective sonosensitization and tumor hypoxia relief enable synergistic sonodynamic-immunotherapy
Yang, Zhijuan2; Tao, Danlei2; Zhong, Wenzhao1; Liu, Zhuang2; Feng, Liangzhu1,2; Chen, Meiwan1
2022-01
Source PublicationBiomaterials
ISSN0142-9612
Volume280
Abstract

Relieving tumor hypoxia has recently been found to be a promising approach to reverse tumor immunosuppression and thus enhance the treatment outcomes of diverse cancer treatments. Herein, we prepared a type of fluorinated covalent conjugate polymers (COPs) with sonosensitizer meso-5, 10, 15, 20-tetra (4-hydroxylphenyl) porphyrin (THPP) and perfluorosebacic acid (PFSEA) as cross-linkers, yielding THPP-COPs with efficient sonodynamic efficacy and loading capacity towards perfluoro-15-crown-5-ether (PFCE), a model perfluorocarbon molecule. Upon intratumoral injection, such PFCE@THPP-COPs could not only attenuate tumor hypoxia, but also exhibit the most effective suppression effect on tumor growth in the presence of ultrasound exposure by inducing immunogenic cell death of cancer cells. Furthermore, we found that the sonodynamic therapy of PFCE@THPP-COPs together with anti-CD47 immunotherapy would synergistically suppress tumor growth by increasing the tumor-infiltrating frequencies of phagocytic M1 macrophages and cytotoxic CD3CD8 T cells, while reducing the frequency of immunosuppressive regulatory T cells. Moreover, such combination treatment could also elicit potent protective memory antitumor immunity to prevent tumor challenge. Therefore, this work presents PFCE@THPP-COPs are a type of multifunctional nano-sonosensitizers potent in removing negative impacts of inherent tumor hypoxia and immunosuppression, and suppressing tumor growth and tumor recurrence by priming host's antitumor immunity, particularly in synergizing with anti-CD47 immunotherapy.

KeywordFluorinated Covalent Conjugate Polymers Immunotherapy Sonodynamic Therapy Tumor Hypoxia Attenuation
DOI10.1016/j.biomaterials.2021.121250
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaEngineering ; Computer Science
WOS SubjectEngineering, Biomedical ; Materials Science, bioMaterials
WOS IDWOS:000783917000001
Scopus ID2-s2.0-85119599209
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Cited Times [WOS]:11   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorFeng, Liangzhu; Chen, Meiwan
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
2.Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Yang, Zhijuan,Tao, Danlei,Zhong, Wenzhao,et al. Perfluorocarbon loaded fluorinated covalent organic polymers with effective sonosensitization and tumor hypoxia relief enable synergistic sonodynamic-immunotherapy[J]. Biomaterials,2022,280.
APA Yang, Zhijuan,Tao, Danlei,Zhong, Wenzhao,Liu, Zhuang,Feng, Liangzhu,&Chen, Meiwan.(2022).Perfluorocarbon loaded fluorinated covalent organic polymers with effective sonosensitization and tumor hypoxia relief enable synergistic sonodynamic-immunotherapy.Biomaterials,280.
MLA Yang, Zhijuan,et al."Perfluorocarbon loaded fluorinated covalent organic polymers with effective sonosensitization and tumor hypoxia relief enable synergistic sonodynamic-immunotherapy".Biomaterials 280(2022).
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