Immunogenic nanomedicine based on GSH-responsive nanoscale covalent organic polymers for chemo-sonodynamic therapy

Fengyun Shen; Danlei Tao; Rui Peng; Yao He; Zhuang Liu; Jiansong Ji; Liangzhu Feng

doi:10.1016/j.biomaterials.2022.121428

Immunogenic nanomedicine based on GSH-responsive nanoscale covalent organic polymers for chemo-sonodynamic therapy

Biomaterials. 2022 Apr:283:121428. doi: 10.1016/j.biomaterials.2022.121428. Epub 2022 Feb 17.

Authors

Fengyun Shen¹, Danlei Tao¹, Rui Peng¹, Yao He¹, Zhuang Liu¹, Jiansong Ji², Liangzhu Feng³

Affiliations

¹ Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu, 215123, China.
² Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, School of Medicine, Lishui Hospital of Zhejiang University, Lishui, 323000, China.
³ Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu, 215123, China. Electronic address: lzfeng@suda.edu.cn.

PMID: 35219148
DOI: 10.1016/j.biomaterials.2022.121428

Abstract

Sonodynamic therapy (SDT) is emerging as a non-invasive strategy to eradicate tumors, but its therapeutic efficacy is still not ideal. To achieve more effective SDT, water insoluble sonosensitizer meso-5, 10, 15, 20-tetra(4-hydroxylphenyl)porphyrin (THPP) is here esterified with succinic acid conjugated oxaliplatin prodrug (Oxa(IV)SA₂) and carboxyl group terminated PEG (PEG_5k-COOH). The obtained covalent organic polymer (COP) of THPP-Oxa(IV)-PEG with good physiological stability, sonosensitization efficacy and glutathione (GSH) responsive oxalipatin responsive behaviors can induce effective immunogenic cancer cell death upon the ultrasound exposure. In addition, THPP-Oxa(IV)-PEG is shown to be a versatile carrier for both hydrophobic near infrared dye and radioisotope ^99mTc, thereby enabling real-time tracking of its pharmacokinetics behavior under corresponding imaging facilities. Furthermore, treatment with THPP-Oxa(IV)-PEG injection and ultrasound exposure is shown to be most effectively in suppressing tumor growth, with 3 of 6 CT26 tumor bearing mice fully cured, ascribing to its high potency in eliciting profound antitumor immune responses. This work highlights a promising strategy in constructing multifunctional nanosonosensitizer as a potent immunogenic nanomedicine to enhance the treatment outcome of SDT.

Keywords: Chemo-sonodynamic therapy; Covalent-organic polymers; Immunogenic nanomedicine; Oxaliplatin prodrug.

Publication types

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

MeSH terms

Animals
Cell Line, Tumor
Glutathione
Mice
Nanomedicine*
Nanoparticles* / chemistry
Polymers

Substances

Polymers
Glutathione