title: Liposomal Nanoparticles Carrying anti-IL6R Antibody to the Tumour Microenvironment Inhibit Metastasis in Two Molecular Subtypes of Breast Cancer Mouse Models.
abstract: Tumour microenvironment (TME) contributes significantly towards potentiating the stemness and metastasis properties of cancer cells. IL6-Stat3 is one of the important cell signaling pathways in mediating the communication between tumour and immune cells. Here, we have systematically developed a novel anti-CD44 antibody-mediated liposomal nanoparticle delivery system loaded with anti-IL6R antibody, which could specifically target the TME of CD44+breast cancer cells in different mouse models for triple negative and luminal breast cancer. This nanoparticle had an enhanced and specific tumour targeting efficacy with dramatic anti-tumour metastasis effects in syngeneic BALB/c mice bearing 4T1 cells as was in the syngeneic MMTV-PyMT mice. It inhibited IL6R-Stat3 signaling and moderated the TME, characterized by the reduced expression of genes encoding Stat3, Sox2, VEGFA, MMP-9 and CD206 in the breast tissues. Furthermore, this nanoparticle reduced the subgroups of Sox2+and CD206+cells in the lung metastatic foci, demonstrating its inhibitory effect on the lung metastatic niche for breast cancer stem cells. Taken together, the CD44 targeted liposomal nanoparticles encapsulating anti-IL6R antibody achieved a significant effect to inhibit the metastasis of breast cancer in different molecular subtypes of breast cancer mouse models. Our results shed light on the application of nanoparticle mediated cancer immune-therapy through targeting TME.
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Guo
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Gao
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Antao
authors.initials: A
authors.lastname: Chang
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Ye
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Immunology, Institute of Basic Medical Science, Peking Union Medical College, Beijing 100730, China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu 610041, China.
authors.forename: Shengyong
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Sun
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China;; Tianjin Key Laboratory of Tumour Microenvironment and Neurovascular Regulation, Tianjin 300071, China.; Collaborative Innovation Center for Biotherapy, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China;; Tianjin Key Laboratory of Tumour Microenvironment and Neurovascular Regulation, Tianjin 300071, China.; Collaborative Innovation Center for Biotherapy, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000556:secondary; D004195:Disease Models, Animal; D018960:Hyaluronan Receptors / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage*; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000906:Antibodies; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D008081:Liposomes; D019947:Receptors, Interleukin-6
keywords: anti-IL6R antibody; liposomal nanoparticles; metastasis; metastatic niche.; tumour microenvironment