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.

Thrombus has long been the major contributor of death and disability because it can cause adverse effects to varying degrees on the body, resulting in vascular blockage, embolism, heart valve deformation, widespread bleeding, etc. However, clinically, conventional thrombolytic drug treatments have hemorrhagic complication risks and easy to miss the best time of treatment window. Thus, it is an urgent need to investigate newly alternative treatment strategies that can reduce adverse effects and improve treatment effectiveness. Drugs based on nanomaterials act as a new biomedical strategy and promising tools, and have already been investigated for both diagnostic and therapeutic purposes in thrombus therapy. Recent studies have some encouraging progress. In the present review, we primarily concern with the latest developments in the areas of nanomedicines targeting thrombosis therapy. We present the thrombus\' formation, characteristics, and biomarkers for diagnosis, overview recent emerging nanomedicine strategies for thrombus therapy, and focus on the future design directions, challenges, and prospects in the nanomedicine application in thrombus therapy.