Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Nanoscale. 2021 Apr 21;13(15):7389-7402. doi: 10.1039/d1nr01008e. Epub 2021 Apr 13.
Metal-organic frameworks (MOFs) as promising materials have been widely used in drug delivery, disease diagnosis and therapy; however, their effects on the reproductive system remain unknown, which hinders their further clinical applications. Here we show that repeated subcutaneous injections of copper MOFs (HKUST-1) induce higher toxicity into the male reproductive system relative to the female reproductive system, with disrupted seminiferous tubule histology, sperm generation disorder, irreversible sperm morphological abnormities and reduced pregnancy rate but only slight follicle dysfunction and pregnancy complications in female mice. Interestingly, the modification of HKUST-1 with folic acid attenuates the reproductive toxicity and even improves pregnancy and fetus development. This study confirms the gender-dependent toxicity of HKUST-1 to the reproductive system, and that folic acid modification could relieve the reproductive toxicity, thus providing us a deep understanding of reproductive toxicity of copper MOFs, and also a guideline and feasible way to improve the biocompatibility of copper MOFs for potential medical use.
金属-有机骨架（MOFs）作为有前途的材料，已被广泛应用于药物输送、疾病诊断和治疗；然而，其对生殖系统的影响尚不清楚，这阻碍了它们在临床上的进一步应用。在这里，我们发现，与雌性生殖系统相比，重复皮下注射铜 MOFs（HKUST-1）会对雄性生殖系统造成更高的毒性，导致生精小管组织学紊乱、精子生成障碍、精子形态不可逆转异常和妊娠率降低，但对雌性小鼠的卵泡功能和妊娠并发症只有轻微影响。有趣的是，用叶酸对 HKUST-1 进行修饰可以减轻其生殖毒性，甚至可以提高妊娠率和胎儿发育。本研究证实了 HKUST-1 对生殖系统的性别依赖性毒性，并且叶酸修饰可以减轻生殖毒性，从而使我们深入了解铜 MOFs 的生殖毒性，也为提高铜 MOFs 的生物相容性以用于潜在的医学用途提供了指导和可行的方法。
