Nanostrategy of Targeting at Embryonic Trophoblast Cells Using CuO Nanoparticles for Female Contraception
- Zhenning Su
Zhenning SuNHC Key Laboratory of Reproductive Health Engineering Technology Research, Department of Reproduction Physiology, National Research Institute for Family Planning, Beijing 100081, ChinaGraduate School of Peking Union Medical College, Beijing 100730, ChinaMore by Zhenning Su
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- Cancan Yao
Cancan YaoNHC Key Laboratory of Reproductive Health Engineering Technology Research, Department of Reproduction Physiology, National Research Institute for Family Planning, Beijing 100081, ChinaGraduate School of Peking Union Medical College, Beijing 100730, ChinaMore by Cancan Yao
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- Joanne Tipper
Joanne TipperSchool of Biomedical Engineering, Faculty of Engineering and Information Technology, University of Technology Sydney, Sydney, New South Wales 2007, AustraliaMore by Joanne Tipper
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- Lijun Yang
Lijun YangNHC Key Laboratory of Reproductive Health Engineering Technology Research, Department of Reproduction Physiology, National Research Institute for Family Planning, Beijing 100081, ChinaGraduate School of Peking Union Medical College, Beijing 100730, ChinaMore by Lijun Yang
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- Xiangbo Xu
Xiangbo XuNHC Key Laboratory of Reproductive Health Engineering Technology Research, Department of Reproduction Physiology, National Research Institute for Family Planning, Beijing 100081, ChinaMore by Xiangbo Xu
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- Xihua Chen
Xihua ChenNHC Key Laboratory of Reproductive Health Engineering Technology Research, Department of Reproduction Physiology, National Research Institute for Family Planning, Beijing 100081, ChinaMore by Xihua Chen
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- Guo Bao
Guo BaoNHC Key Laboratory of Reproductive Health Engineering Technology Research, Department of Reproduction Physiology, National Research Institute for Family Planning, Beijing 100081, ChinaMore by Guo Bao
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- Bin He*
Bin He*Email: [email protected]NHC Key Laboratory of Reproductive Health Engineering Technology Research, Department of Reproduction Physiology, National Research Institute for Family Planning, Beijing 100081, ChinaMore by Bin He
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- Xiaoxue Xu*
Xiaoxue Xu*Email: [email protected]School of Biomedical Engineering, Faculty of Engineering and Information Technology, University of Technology Sydney, Sydney, New South Wales 2007, AustraliaSchool of Science, Western Sydney University, Sydney, New South Wales 2751, AustraliaMore by Xiaoxue Xu
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- Yufeng Zheng*
Yufeng Zheng*Email: [email protected]School of Materials Science and Engineering, Peking University, Beijing 100871, ChinaInternational Research Organization for Advanced Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555, JapanMore by Yufeng Zheng
Abstract
Effective contraceptives have been comprehensively adopted by women to prevent the negative consequences of unintended pregnancy for women, families, and societies. With great contributions of traditional hormonal drugs and intrauterine devices (IUDs) to effective female contraception by inhibiting ovulation and deactivating sperm, their long-standing side effects on hormonal homeostasis and reproductive organs for females remain concerns. Herein, we proposed a nanostrategy for female contraceptives, inducing embryonic trophoblast cell death using nanoparticles to prevent embryo implantation. Cupric oxide nanoparticles (CuO NPs) were adopted in this work to verify the feasibility of the nanostrategy and its contraceptive efficacy. We carried out the in vitro assessment on the interaction of CuO NPs with trophoblast cells using the HTR8/SVneo cell line. The results showed that the CuO NPs were able to be preferably uptaken into cells and induced cell damage via a variety of pathways including oxidative stress, mitochondrial damage, DNA damage, and cell cycle arrest to induce cell death of apoptosis, ferroptosis, and cuproptosis. Moreover, the key regulatory processes and the key genes for cell damage and cell death caused by CuO NPs were revealed by RNA-Seq. We also conducted in vivo experiments using a rat model to examine the contraceptive efficacy of both the bare CuO NPs and the CuO/thermosensitive hydrogel nanocomposite. The results demonstrated that the CuO NPs were highly effective for contraception. There was no sign of disrupting the homeostasis of copper and hormone, or causing inflammation and organ damage in vivo. In all, this nanostrategy exhibited huge potential for contraceptive development with high biosafety, efficacy, clinical translation, nonhormonal style, and on-demand for women.
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