A nanodrug incorporating siRNA PD-L1 and Birinapant for enhancing tumor immunotherapy

被引：9

作者：

Gong, Tingting ^{[1
,2
,3
]}

Cai, Yujun ^{[4
]}

Sun, Fengze ^{[5
]}

Chen, Jiaxin ^{[1
]}

Su, Zhongzhen ^{[1
,2
,3
]}

Shuai, Xintao ^{[4
]}

Shan, Hong ^{[2
,3
,6
]}

机构：

[1] Sun Yat Sen Univ, Affiliated Hosp 5, Dept Ultrasound, Zhuhai 519000, Peoples R China

[2] Sun Yat Sen Univ, Guangdong Prov Key Lab Biomed Imaging, Affiliated Hosp 5, Zhuhai, Peoples R China

[3] Sun Yat Sen Univ, Guangdong Prov Engn Res Ctr Mol Imaging, Affiliated Hosp 5, Zhuhai, Peoples R China

[4] Sun Yat Sen Univ, Sch Mat Sci & Engn, PCFM Lab, Minist Educ, Guangzhou 510275, Peoples R China

[5] Sun Yat Sen Univ Canc Ctr, Collaborat Innovat Ctr Canc Med, Dept Biotherapy, State Key Lab Oncol Southern China, Guangzhou 510000, Peoples R China

[6] Sun Yat Sen Univ, Affiliated Hosp 5, Dept Intervent Med, Zhuhai 519000, Peoples R China

来源：

BIOMATERIALS SCIENCE | 2021年 / 9卷 / 23期

基金：

中国国家自然科学基金;

关键词：

BREAST-CANCER; DOUBLE-BLIND; PEMBROLIZUMAB; CHEMOTHERAPY; INHIBITORS;

D O I：

10.1039/d1bm01299a

中图分类号：

TB3 [工程材料学]; R318.08 [生物材料学];

学科分类号：

0805 ; 080501 ; 080502 ;

摘要：

Triple-negative breast cancer (TNBC) is associated with a worse prognosis and higher mortality than other breast cancers, and intensive effort has been made to develop therapies targeting TNBC. TNBC shows higher expression levels of programmed cell death ligand 1 (PD-L1) than other breast cancer types, which leads to a decrease in the killing effects of CD8(+) T cells in the tumor microenvironment. Inhibitors of apoptosis proteins (IAPs) could prevent cell death through suppressing caspase activity. Here, Birinapant, an antagonist of IAPs, was found to promote the tumor infiltration of CD8(+) T cells via increasing the secretion of the chemokine CXCL9. In addition, Birinapant could inhibit tumor growth via increasing the secretion of and the sensitivity to TNF-alpha in a TNBC xenotransplantation mouse model. Consequently, liposomes encapsulating Birinapant and siPD-L1 mediated a form of combination therapy based on two drugs to significantly increase the therapeutic effects toward TNBC.

引用

页码：8007 / 8018

页数：12

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