PEGylation effectively improves anti-breast cancer efficiency of heat shock protein gp96 inhibitory polypeptide.

Lulu Liu; Jianwei Gao; Changfei LI; Yue WU; Songdong Meng

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PEGylation effectively improves anti-breast cancer efficiency of heat shock protein gp96 inhibitory polypeptide.

Author: Lulu LIU ¹ ; Jianwei GAO ² ; Changfei LI ³ ; Yue WU ⁴ ; Songdong MENG ³
Author Information

1. Institutes of Physical Science and Information Technology, Anhui University, Hefei 230039, Anhui, China.
2. Cominghealth Biotechnology Co. Ltd., Beijing 100101, China.
3. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
4. Foshan Heat Shock Biotech Co. Ltd., Foshan 528000, Guangdong, China.
Publication Type:Journal Article
Keywords: PEGylation of peptide; cancer; cell membrane gp96; inhibitory peptide; triple-negative breast cancer
MeSH: Adenosine Triphosphate; Female; Heat-Shock Proteins; Humans; Peptides/pharmacology*; Polyethylene Glycols; Triple Negative Breast Neoplasms/pathology*
From: Chinese Journal of Biotechnology 2022;38(9):3363-3378
CountryChina
Language:Chinese
Abstract: Breast cancer is the most common tumor in female, which seriously threatens the health of women. Triple-negative breast cancer is a subtype with the worst prognosis because of its special physiological characteristics and lack of targeted drugs. Therefore, it is urgent to develop new targeted treatments to improve the prognosis and survival rate of the patients. Previous studies have shown that heat shock protein gp96 is expressed on the membrane of a variety of cancer cells but not on the normal cells. Cell membrane gp96 levels are closely related to the poor prognosis of breast cancer, which may serve as a new target for breast cancer treatment. Based on the structure of gp96, we designed an α-helical peptide p37 that specifically targeting the ATP binding region of gp96. To improve the stability and decrease the degradation of the peptide, the N-terminus or C-terminus of p37 was coupled to PEG₂₀₀₀ or PEG₅₀₀₀ respectively, and four PEGylated polypeptides were obtained: mPEG₂₀₀₀CY, mPEG₅₀₀₀CY, mPEG₂₀₀₀LC, and mPEG₅₀₀₀LC. The PEGylated polypeptides inhibited the proliferation and invasion of breast cancer cell SK-BR-3, among which mPEG₂₀₀₀CY showed the most significant inhibitory effect. The half-life of mPEG₂₀₀₀CY in vivo was significantly longer than p37, and it effectively inhibited the growth of xenografted tumors of triple-negative breast cancer MDA-MB-231. The results provide a basis for the development of new targeted drugs against breast cancer, especially the triple-negative breast cancer.