title: Tumor Microenvironment Activated Membrane Fusogenic Liposome with Speedy Antibody and Doxorubicin Delivery for Synergistic Treatment of Metastatic Tumors.
abstract: Metastasis is the principal event leading to breast cancer death. Discovery of novel therapeutic approaches that are specific in targeting tumor metastasis factors while at the same time are an effective treatment of the tumor is urgently required. S100A4 protein is a key player in promoting metastasis and sequestrating the effect of tumor-suppressor protein p53. Here, a tumor microenvironment activated membrane fusogenic liposome was prepared to deliver rapidly anti-S100A4 antibody and doxorubicin into the cytoplasm directly in a fusion-dependent manner in order to bypass the cellular endocytosis to avoid the inefficient escape and degradation in the acidic endosome. After intracellular S100A4 blockage with anti-S100A4 antibody, the cytoskeleton of breast cancer 4T1 cells was rearranged and cell motility was suppressed. In the meantime, the antitumor effect of doxorubicin was enormously enhanced by reversing the effect of S100A4 on the sequestration of tumor-suppressor protein p53. Importantly, both local growth and metastasis of 4T1 cells were inhibited in a xenograft mouse model. Together, the speedy delivery of antibody and doxorubicin into cytoplasm based on a new membrane fusogenic liposome was an innovative approach for metastatic breast cancer treatment.
authors.affiliation: The First Affiliated Hospital of Zhengzhou University , No.1 Jianshe East Road, Zhengzhou 450052, Henan Province, China.|Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.|Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences , Beijing, 100101, China.
authors.forename: Hongzhang
authors.initials: H
authors.lastname: Deng
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences , Beijing, 100101, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences , Beijing, 100101, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital of Zhengzhou University , No.1 Jianshe East Road, Zhengzhou 450052, Henan Province, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.
authors.forename: Jianhua
authors.identifier: http://orcid.org/0000-0001-7833-9715
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.
authors.forename: Anjie
authors.initials: A
authors.lastname: Dong
authors.affiliation: The First Affiliated Hospital of Zhengzhou University , No.1 Jianshe East Road, Zhengzhou 450052, Henan Province, China.|Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences , Beijing, 100101, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
mesh_terms: D000818:Animals; D000906:Antibodies; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D004317:Doxorubicin; D006801:Humans; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D059016:Tumor Microenvironment
chemical_list: D000906:Antibodies; D008081:Liposomes; D004317:Doxorubicin
keywords: DOX; antibody; fusogenic liposome; metastasis; tumor microenvironment