Programmable double-unlock nanocomplex self-supplies phenylalanine ammonia-lyase for precise phenylalanine deprivation of tumors

作     者：Chunqing Ou Meijia Xiao Xinyue Zheng Xianzhou Huang Suleixin Yang Yingying Leng Xiaowei Liu Xiuqi Liang Linjiang Song Yanjie You Shaohua Yao Changyang Gong Chunqing Ou;Meijia Xiao;Xinyue Zheng;Xianzhou Huang;Suleixin Yang;Yingying Leng;Xiaowei Liu;Xiuqi Liang;Linjiang Song;Yanjie You;Shaohua Yao;Changyang Gong

作者机构：Department of BiotherapyCancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoAvenida da UniversidadeTaipaMacao 999087China School of Medical and Life SciencesChengdu University of Traditional Chinese MedicineChengdu 611137China Department of GastroenterologyPeople’s Hospital of Ningxia Hui Autonomous RegionYinchuan 750002China 

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

年 卷 期：2024年第35卷第8期

页      面：455-459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 by funds of Sichuan Province for Distinguished Young Scholar(No.2021JDJQ0037) the National Natural Science Foundation of China(No.82172094) 

主　　题：Programmable double-unlock Essential amino acids deprivation Phenylalanine ammonia-lyase Self-supply Gene therapy 

摘      要：Essential amino acids(EAAs)deprivation is a potential antitumor approach because EAAs are critical for tumor *** efficiently inhibit tumor growth,continuous deprivation of EAAs is required,how-ever,continuous deprivation without precise control will introduce toxicity to normal ***,a programmable double-unlock nanocomplex(ROCK)was prepared,which could self-supply phenylalanine ammonia-lyase(PAL)to tumor cells for phenylalanine(Phe)*** was double-locked in physiological conditions when administered *** ROCK actively targeted to tumor cells by integrinαvβ3/5 and CD44,ROCK was firstly unlocked by cleavage of protease on tumor cell membrane,exposing CendR and R8 to enhance ***,hyaluronic acid was digested by hyaluronidase overexpressed in endo/lysosome of tumor cells,in which ROCK was secondly unlocked,resulting in pro-moting endo/lysosome escape and PAL plasmid(pPAL)*** pPAL could sustainably express PAL in host tumor cells until the self-supplied PAL precisely and successfully deprived Phe,thereby block-ing the protein synthesis and killing tumor cells ***,our precise Phe deprivation strategy effectively inhibited tumor growth with no observable toxicity to normal cells,providing new insights to efficiently remove intratumoral nutrition for cancer therapy.