Binary prodrug nanoassemblies combining chemotherapy and ferroptosis activation for efficient triple-negative breast cancer therapy  

作　　者：Lin Li Bingjun Sun jin Sun Lin Chen Zhonggui He 

机构地区：[1]Department of Pharmacy,Women and Children's Hospital of Chongqing Medical University/Chongqing Health Center for Women and Children,Chongqing 401147,China [2]Department of Pharmaceutics,Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China

出　　处：《Chinese Chemical Letters》2024年第10期348-352,共5页中国化学快报（英文版）

基　　金：supported by the National Nature Science Foundation of China(No.81803029);the Science and Technology Foundation of Yuzhong District,Chongqing(No.20210179);the Nature Science Foundation of Chongqing(No.cstc2021jcyjmsxmX1089)。

摘　　要：Chemotherapy has been recommended as the standard protocol for triple-negative breast cancer(TNBC)at the advanced stage.However,the current treatment is unsatisfactory due to inefficient drug accumulation and rapid chemo-resistance.Thus,rational design of advanced drug delivery systems that can induce multiple cell death pathways is a promising strategy to combat TNBC.Ferroptosis is a powerful non-apoptotic cell death modality,showing potential in tumor inhibition.Herein,we propose a binary prodrug nanoassemblies that combines chemotherapy with ferroptosis for TNBC treatment.In this system,paclitaxel is linked with paracetamol(ferroptosis activator)by a disulfide linkage to construct self-assembly prodrug.Meanwhile,2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-methyl(polyethylene glycol)-2000-tyrosine(DSPE-PEG2k-tyrosine)is applied for large neutral amino acid transporter 1(LAT1)targeting,which is highly expressed in TNBC.The prodrug nanoassemblies exhibit good stability and a glutathione(GSH)-responsive release profile.Furthermore,the LAT1-targeted nanoassemblies show stronger cytotoxicity,higher cellular uptake,and more obvious ferroptosis activation than non-decorated ones.In a TNBC mice model,the prodrug nanoassemblies demonstrate strong anti-tumor efficacy.The application of ferroptosis-assisting chemotherapy may provide a promising strategy for TNBC therapy.

关 键 词：Prodrug nanoassemblies PACLITAXEL Ferroptosis LAT1 Triple-negative breast cancer 

分 类 号：TB383.1[一般工业技术—材料科学与工程] R737.9[医药卫生—肿瘤]