Ferritin-Nanocaged ATP Traverses the Blood-Testis Barrier and Enhances Sperm Motility in an Asthenozoospermia Model.
Ferritin-Nanocaged ATP Traverses the Blood-Testis Barrier and Enhances Sperm Motility in an Asthenozoospermia Model.
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DOI：
10.1021/acsnano.1c10029
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发表时间：
2022-02
期刊：
影响因子：
17.1
通讯作者：
Jing Pang;Xu Feng;Qian Liang;Xiaoyan Zheng;Yiman Duan;Xin Zhang;Jubiao Zhang;Yang Chen
中科院分区：
文献类型：
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作者：
Jing Pang;Xu Feng;Qian Liang;Xiaoyan Zheng;Yiman Duan;Xin Zhang;Jubiao Zhang;Yang Chen
在体外受精过程中加入外源性ATP可提高精子活力。然而，在体内弱精子症治疗中，向睾丸施用外源性ATP以提高精子活力尚未被研究。受纳米医学最新进展的启发，我们研究了药物递送纳米载体穿过血睾屏障（BTB）的能力是否可以促进ATP依赖性弱精子症的治疗。我们发现，人H-铁蛋白（HFn）纳米载体具有穿越BTB的能力，并特异性靶向细长精子细胞的头部。具体而言，HFn纳米载体穿过BTB并通过与HFn受体（HFR）结合而在精子头部中积累，HFn受体（HFR）在支持细胞中的表达相对较低，但在精子头部中的表达较高。在棉酚诱导的小鼠弱精子症模型中，通过尾静脉注射施用负载ATP的HFn纳米笼显著改善了精子活力。此外，HFn纳米载体在短期（1d）和长期（30 d，90d）对小鼠无毒性，也不影响其生殖健康。因此，负载ATP的HFn纳米载体可潜在地用作治疗弱精子症的药物递送系统。
Sperm motility can be enhanced by adding ATP exogenously during in vitro fertilization. However, administering exogenous ATP to the testis to improve sperm motility for in vivo asthenozoospermia treatment has not been investigated yet. Inspired by the recent advances in nanomedicine, we investigated whether the capability of drug delivery nanocarriers to traverse the blood-testis barrier (BTB) can facilitate ATP-dependent asthenozoospermia treatment. We found that the human H-ferritin (HFn) nanocarrier possesses the capability to traverse the BTB and specifically targets the head of elongated sperm cells. Specifically, the HFn nanocarrier traversed the BTB and accumulated in the sperm heads by binding with the HFn receptor (HFR), whose expression was relatively low in Sertoli cells but high in sperm heads. In a gossypol-induced mouse asthenozoospermia model, the administration of an ATP-loaded HFn nanocage through a tail vein injection significantly improved sperm motility. Moreover, the HFn nanocarrier was not toxic to mice in the short (1d) and long terms (30d, 90d) nor did it affect their reproductive health. Thus, the ATP-loaded HFn nanocarrier can potentially serve as a drug-delivery system for treating asthenozoospermia.