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Quercetin encapsulated in folic acid-modified liposomes is therapeutic against osteosarcoma by non-covalent binding to the JH2 domain of JAK2 Via the JAK2-STAT3-PDL1

文献类型： 外文期刊

作者： Jing, Doudou 1 ; Wu, Wei 1 ; Chen, Xuanzuo 1 ; Xiao, Hongwei 3 ; Zhang, Zhenhao 1 ; Chen, Fengxia 4 ; Zhang, Zhicai 1 ; Liu, Jianxiang 1 ; Shao, Zengwu 1 ; Pu, Feifei 1 ;

作者机构： 1.Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Orthoped, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China

2.Shanxi Med Univ, Dept Orthopaed, Hosp 2, Taiyuan 030001, Shanxi, Peoples R China

3.Hubei Acad Agr Sci, Inst Anim Sci & Vet Med, Key Lab Anim Embryo Engn & Mol Breeding Hubei Pro, Wuhan 430064, Hubei, Peoples R China

4.Wuhan Univ, Zhongnan Hosp, Dept Radiat & Med Oncol, Wuhan 430071, Hubei, Peoples R China

关键词： Osteosarcoma; Liposome quercetin; JAK2-STAT3; PD-L1; Immune escape

期刊名称：PHARMACOLOGICAL RESEARCH （ 影响因子：10.334； 五年影响因子：9.105 ）

ISSN： 1043-6618

年卷期： 2022 年 182 卷

页码：

收录情况： SCI

摘要： Osteosarcoma (OS) is a malignant solid tumor prone to lung metastasis that occurs in adolescents aged 15-19 years. Neoadjuvant chemotherapy and surgical treatment aimed at curing OS have gained limited progress over the last 30 years. Exploring new effective second-line therapies for OS patients is a serious challenge for researchers. Quercetin, a multiple biologically active polyphenolic flavonoid, has been used in tumor therapy. However, the exact mechanism of quercetin is still unknown, which limits the application of quercetin. In the current study, we found that quercetin could inhibit JAK2 through the JH2 domain in a non-covalent manner, resulting in the inhibition of OS proliferation and immune escape via the JAK2-STAT3-PD-L1 signaling axis. More importantly, to overcome the shortcomings of quercetin, including low water solubility and low oral availability, we encapsulated it with folic acid-modified liposomes. The transportation of quercetin by folic acid-modified liposomes may provide a feasible strategy to cure OS.

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