title: Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment.
abstract: Specific targeting and cellular internalization are key properties for carriers of antitumor therapeutic agents. Here, we develop a drug carrier through the attachment of substrate of endoprotease legumain, alanine-alanine-asparagine (AAN), to cell-penetrating peptides (TAT, trans-activating factor). The addition of the AAN moiety to the fourth lysine in the TAT creates a branched peptide moiety, which leads to a decrease in the transmembrane transport capacity of TAT by 72.65%. Legumain efficiently catalyses the release of TAT-liposome from the AAN-TAT-liposome and thereby recovers the penetrating capacity of TAT. Doxorubicin carried by the AAN-TAT-liposome led to an increase in the tumoricidal effect of doxorubicin and a reduction in its systemic adverse effects in comparison with doxorubicin carried by a control delivery system. Thus, the specific targeting and high efficiency of this delivery platform offers a novel approach to limit the toxicity of anticancer agents as well as increasing their efficacy in cancer therapy.
authors: Department of Immunology, Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Ze
authors: Z
authors: Liu
authors: Department of Pathology, Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Min
authors: M
authors: Xiong
authors: Tianjin Key Laboratory of Modern Drug Delivery and High Efficiency in Tianjin University, 92 Weijin Road, Tianjin 300072, China.
authors: Junbo
authors: J
authors: Gong
authors: Department of Immunology, Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Yan
authors: Y
authors: Zhang
authors: Department of Immunology, Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Nan
authors: N
authors: Bai
authors: Department of Immunology, Beijing Union Medical School, 5 Dong Dan San Tiao, Beijing 100010, China.
authors: Yunping
authors: Y
authors: Luo
authors: Department of Immunology, Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Luyuan
authors: L
authors: Li
authors: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors: Yuquan
authors: Y
authors: Wei
authors: Department of Immunology, Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Yanhua
authors: Y
authors: Liu
authors: Department of Pathology, Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Xiaoyue
authors: X
authors: Tan
authors: Department of Immunology, Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Rong
authors: R
authors: Xiang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage*; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D053758:Nanoparticles; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*; D000099240:Asparaginyl Endopeptidase
chemical_list: D000903:Antibiotics, Antineoplastic; D003546:Cysteine Endopeptidases; D004317:Doxorubicin; D008081:Liposomes; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099240:Asparaginyl Endopeptidase