Exosomes containing miRNAs targeting HER2 synthesis and engineered to adhere to HER2 on tumor cells surface exhibit enha
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Journal of Nanobiotechnology Open Access
RESEARCH
Exosomes containing miRNAs targeting HER2 synthesis and engineered to adhere to HER2 on tumor cells surface exhibit enhanced antitumor activity Lei Wang1, Xusha Zhou1, Weixuan Zou1, Yinglin Wu1, Jing Zhao2, Xiaoqing Chen2* and Grace Guoying Zhou1,2*
Abstract Background: Exosomes are small, cellular membrane-derived vesicles with a diameter of 50–150 nm. Exosomes are considered ideal drug delivery systems with a wide range of applications in various diseases, including cancer. However, nonspecific delivery of therapeutic agents by exosomes in vivo remains challenging. Human epidermal growth factor receptor 2 (HER2) is an epidermal growth factor receptor tyrosine kinase, and its overexpression is usually associated with cell survival and tumor progression in various cancers. In this study, we aim to develop novel exosomes with dual HER2-targeting ability as a nanoparticle delivery vehicle to enhance antitumor efficacy in vivo. Results: Here, we report the generation of two kinds of exosomes carrying miRNAs designed to block HER2 synthesis, which consequently showed a distinct anti-tumor effect. The 293-miR-HER2 exosomes package and deliver miRNAs targeting HER2 to recipient cells to block HER2 synthesis. The anti-tumor effect of these exosomes on cancer cells dependent on HER2 for survival but do not affect cells that lack HER2 or that are engineered to express HER2 but are not dependent on it for survival. In contrast, 293-miR-XS-HER2 exosomes carry an additional peptide, which enables them to adhere to HER2 on the surface of cancer cells. Consequently, these exosomes preferentially enter these cells with surface expression of HER2 and further displayed a tumoricidal effect. The 293-miR-XS-HER2 exosomes are significantly more effective than the 293-miR-HER2 exosomes in shrinking HER2-positive tumors implanted in mice. Conclusions: Collectively, as novel antitumor drug delivery vehicles, HER2 dual-targeting exosomes exhibit increased target-specific delivery efficiency and can be further utilized to develop new nanoparticle-based targeted therapies. Keywords: Exosomes, HER2, miRNA, Targeted delivery, HER2-positive tumor, Intravenous injection
Background In this communication, we report the construction of exosomes designed to preferentially enter and ultimately *Correspondence: [email protected]; [email protected] 2 Shenzhen International Institute for Biomedical Research, Longhua District, 1301 Guanguang Rd. 3F Building 1‑B, Silver Star Hi‑tech Park, Shenzhen 518116, Guangdong, China Full list of author information is available at the end of the article
displayed tumoricidal effects on cancer cells dependent on human epidermal growth factor receptor 2 (HER2) for their survival. The following concepts are relevant to this report: HER2 is a member of the human epidermal growth factor receptor family [1–3]. The HER2 protein is expressed at high levels on the surface of human breast cancer cells. Its role in the oncogenic behaviors of these cells is suppor
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