Theranostics 2017; 7(3):775-788. doi:10.7150/thno.17237
Liposomal Nanoparticles Carrying anti-IL6R Antibody to the Tumour Microenvironment Inhibit Metastasis in Two Molecular Subtypes of Breast Cancer Mouse Models
1. School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China;
2. Department of Immunology, Institute of Basic Medical Science, Peking Union Medical College, Beijing 100730, China;
3. State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu 610041, China.
4. Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
5. Tianjin Key Laboratory of Tumour Microenvironment and Neurovascular Regulation, Tianjin 300071, China.
6. Collaborative Innovation Center for Biotherapy, Nankai University, 94 Weijin Road, Tianjin 300071, China.
* Chunlei Guo and Yanan Chen contributed equally to this paper.
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.
Keywords: liposomal nanoparticles, anti-IL6R antibody, tumour microenvironment, metastasis, metastatic niche.
Guo C, Chen Y, Gao W, Chang A, Ye Y, Shen W, Luo Y, Yang S, Sun P, Xiang R, Li N. Liposomal Nanoparticles Carrying anti-IL6R Antibody to the Tumour Microenvironment Inhibit Metastasis in Two Molecular Subtypes of Breast Cancer Mouse Models. Theranostics 2017; 7(3):775-788. doi:10.7150/thno.17237. Available from http://www.thno.org/v07p0775.htm