Exosomes synthesizing HER2 miRNA and engineered to adhere to HER2 on surface tumor cells exhibit enhanced anti-tumor activity [post]

Lei Wang, Xusha Zhou, Weixuan Zou, Yinglin Wu, Jing Zhao, Xiaoqing Chen, Grace Guoying Zhou
2020 unpublished
Introduction: Exosomes are small vesicles derived from cellular membranes with a diameter of 50–150 nm. Exosomes are considered to be ideal drug delivery systems with a wide range of application in various diseases including cancer. However, nonspecific delivery of therapeutic agents by exosomes in vivo remains a challenging. Human epidermal growth factor receptor 2 (HER2) is an epidermal growth factor receptor tyrosine kinase. Overexpression of HER2 is usually associated with cancer survival
more » ... h cancer survival and progression in various cancers. In this study, we aimed to develop the novel exosomes with dual HER2-targeting ability as nanoparticle delivery vehicle to enhance anti-tumor efficacy in vivo.Results Here we report the construction of two kinds of exosomes carrying designed miRNA to block the synthesis of HER2 and as a consequence to kill the tumor cells. The 293-miR-HER2 exosomes package and deliver designed miRNA to cells to block HER2 synthesis. These exosomes kill cancer cells dependent on HER2 for survival but have no effect on cells lacking of HER2 or which were engineered to express HER2 but do not depend on it for survival. The 293-miR-XS-HER2 exosomes carry one more peptide, which enables the exosome to adhere HER2 on the surface of the cancer cells. In consequence these exosomes preferentially enter and kill cells exhibiting HER2 on their surface. The 293-miR-XS-HER2 exosomes are significantly more effective in shrinking the size of HER2-positive tumors implanted in mice than the 293-miR-HER2 exosomes.Conclusion Collectively, as novel anti-tumor drug delivery vehicles, the HER2 dual-targeting exosomes has increased target-specific delivery efficiency, which can be further utilized to develop new nanoparticle targeted therapy.
doi:10.21203/rs.3.rs-39552/v1 fatcat:xpmrhqos5bb3to2cptwt2kcdnm