Perfluorocarbon loaded fluorinated covalent organic polymers with effective sonosensitization and tumor hypoxia relief enable synergistic sonodynamic-immunotherapy

Zhijuan Yang; Danlei Tao; Wenzhao Zhong; Zhuang Liu; Liangzhu Feng; Meiwan Chen

doi:10.1016/j.biomaterials.2021.121250

Perfluorocarbon loaded fluorinated covalent organic polymers with effective sonosensitization and tumor hypoxia relief enable synergistic sonodynamic-immunotherapy

Biomaterials. 2022 Jan:280:121250. doi: 10.1016/j.biomaterials.2021.121250. Epub 2021 Nov 15.

Authors

Zhijuan Yang¹, Danlei Tao¹, Wenzhao Zhong², Zhuang Liu¹, Liangzhu Feng³, Meiwan Chen⁴

Affiliations

¹ Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu Province, 215123, China.
² State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
³ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China; Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu Province, 215123, China. Electronic address: lzfeng@suda.edu.cn.
⁴ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China. Electronic address: mwchen@um.edu.mo.

PMID: 34823883
DOI: 10.1016/j.biomaterials.2021.121250

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_pf-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_pf-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_pf-COPs together with anti-CD47 immunotherapy would synergistically suppress tumor growth by increasing the tumor-infiltrating frequencies of phagocytic M1 macrophages and cytotoxic CD3⁺CD8⁺ 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_pf-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.

Keywords: Fluorinated covalent conjugate polymers; Immunotherapy; Sonodynamic therapy; Tumor hypoxia attenuation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes
Cell Line, Tumor
Fluorocarbon Polymers
Fluorocarbons*
Immunotherapy
Polymers
Tumor Hypoxia*

Substances

Fluorocarbon Polymers
Fluorocarbons
Polymers