Premature ovarian failure (POF) is the most frequently occured disease in ovary. Direct inhibition of mammalian target of rapamycin (mTOR) activity can treat woman POF but brings adverse effects to women. Herein, by rational design of a hydrogelator Nap-Phe-Phe-Asp-Arg-Leu-Tyr-OH (Y) and co-assembling Y with an inhibitor of receptor tyrosine kinase (RTK, an upstream kinase of mTOR), Ala-Glu-Ala-Ala-Leu-Tyr-Lys-Asn-Leu-Leu-His-Ser-OH (Inh), to form hydrogel Gel Y+Inh, we develop a “smart” strategy of RTK-responsive disassembly of the hydrogel to release Inh. Release of Inh moderately inhibits the activity of mTOR and therefore delays ovarian aging. Oocyte and zygote experiments show that Gel Y+Inh improves both meiotic maturation of the oocytes and early embryonic development of the zygotes. In vivo animal experiments indicate that Gel Y+Inh effectively delays ovarian aging in aged mice by down regulation of mTOR activity, stimulation of ovaries to secrete estrogen and progesterone, and development of more antral follicles for reproduction. We expect that our new hydrogel Gel Y+Inh could be applied to treat woman POF, as well as delay ovarian aging, in clinic in the near future.

卵巢早衰（POF）是卵巢中最常见的疾病。直接抑制哺乳动物雷帕霉素靶标（mTOR）的活性可以治疗女性POF，但会给女性带来不良影响。在此，通过合理设计水凝胶化剂Nap-Phe-Phe-Asp-Arg-Leu-Tyr-OH（Y）并将Y与受体酪氨酸激酶（RTK，mTOR的上游激酶）抑制剂共组装，Ala- Glu-Ala-Ala-Leu-Tyr-Lys-Asn-Leu-Leu-His-Ser-OH（Inh），形成水凝胶Gel Y + Inh，我们开发了RTK响应的水凝胶分解的“智能”策略释放Inh。释放Inh适度抑制mTOR的活性，因此延迟卵巢衰老。卵母细胞和合子的实验表明，Gel Y + Inh可以改善卵母细胞的减数分裂成熟和合子的早期胚胎发育。体内动物实验表明，Gel Y + Inh可通过下调mTOR活性，刺激卵巢分泌雌激素和孕酮，以及发育更多的生殖卵泡来延缓衰老小鼠的卵巢衰老。我们希望我们的新型水凝胶Gel Y + Inh可以在不久的将来应用于临床治疗女性POF并延缓卵巢衰老。