Chemo–immunotherapy for chemo-resistance and metastasis of triple-negative breast cancer by combination of iron-oxide nanoparticles and dual-targeting doxorubicin liposomes

作     者：Heping Hu Lijia Yu Zhao Ding Jinsong Ding Yiguo Hu Zongning Yin Heping Hu;Lijia Yu;Zhao Ding;Jinsong Ding;Yiguo Hu;Zongning Yin

作者机构：Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of EducationWest China School of PharmacySichuan UniversityChengdu 610041China Sichuan Huiyu Seacross Medical Technology Co.Ltd.Chengdu 610031China Sichuan Huiyu Pharmaceutical Co.Ltd.Neijiang 641000China Xiangya School of Pharmaceutical SciencesCentral South UniversityChangsha 410013China State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu 610044China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2023年第34卷第10期

页      面：76-81页

核心收录：

学科分类：1002[医学-临床医学] 07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 10[医学] 0702[理学-物理学] 

基　　金：supported financially by the National Natural Science Foundation of China(No.81673363) 

主　　题：Multidrug resistance Multiorgan-specific metastases Immunogenic cell death Intermittent dosing Immunosuppressive tumor microenvironment Tumor-associated macrophages 

摘      要：Triple-negative breast cancer(TNBC)lacks specific regimens for targeted *** chemotherapy promotes the evolution of TNBC into highly chemo-resistant tumors that metastasize to multiple organs ***,polyacrylic acid-coated ultrasmall superparamagnetic iron-oxide nanoparticles(PAA@IONs)and dual-targeting doxorubicin liposomes achieved chemo–immunotherapy through intermittent *** inhibited tumor-drug resistance and multiorgan-specific metastasis significantly by targeting tumors and the *** deciphered an immunosuppressive pre-metastatic niche and discovered that PAA@IONs could target tumors,tumor-draining lymph nodes(TDLNs),the liver,bone,and *** promoted the polarization of macrophages into M1 macrophages in these organs and *** action remodeled the immunosuppressive microenvironment and induced a sustained immune response,thereby reducing organ-specific *** the disadvantages of doxorubicin-induced cardiotoxicity as well as low tumor specificity,dual peptide-modified liposomes could target CD206 and CD13 simultaneously,and reverse *** properties resulted in a significant decrease in the numbers of myeloid-derived suppressor cells(MDSCs)and cancer stem cells(CSCs)in the liver,lungs,and bone,thereby reducing protein expression of Ki-67 in TDLNs,and dramatically increasing the number of cluster of differentiation(CD)8+T cells and CD8+T cell/T-regulatory-cell ratio in tumors and TDLNs(P0.0001).Compared with the control(P0.05 and P0.01,respectively)or free drug(P0.0001 and P0.01,respectively),multi-organ metastases were suppressed significantly,tumor-growth rate reduced,and survival *** drug-delivery system overcame TNBC chemo-resistance and inhibited multiorgan-specific *** circumvents the lack of effective therapeutic targets,the problem of patient selection due to a low mutation rate,and can simultaneously offer the possibility of avoid