Bakhamis Nahla, Awoyemi Toluwalase, Vatish Manu, Townley Helen
Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK.
Department of Engineering Science, University of Oxford, Oxford, UK.
Int J Nanomedicine. 2025 Apr 18;20:4983-4999. doi: 10.2147/IJN.S494710. eCollection 2025.
Iron toxicity is a major contributor to adverse pregnancy outcomes in women with transfusion-dependent thalassemia. Currently used iron chelators are not recommended during pregnancy, as they can cross the placenta causing potential risk to the fetus. However, ceasing medication may adversely affect the mother's health in both the short- and long-term.
We previously demonstrated that melanin nanoparticles can effectively chelate iron, and this has been confirmed by others in iron-overloaded mice. This study aims to assess whether these nanoparticles cross the placenta and evaluate their biocompatibility and haemocompatibility.
A library of 50 nm, 200 nm, and 500 nm melanin nanoparticles were synthesized and coated with Polyethylene Glycol (PEG) to improve their stability. The particles were tested for chelating iron efficacy in and biocompatibility. An in vitro BeWo (choriocarcinoma) cell model and ex vivo human placental perfusion system were used to assess nanoparticle transplacental passage.
Melanin nanoparticles of all sizes were able to chelate iron with a maximum adsorption of 14 mm iron/g of material; significantly higher than Desferrioxamine (DFO) of the same concentration. It was also determined that PEGylated melanin nanoparticles with appropriate size (cut off 200 nm) could be restricted from passing across the placental barrier in an in vitro model using a human choriocarcinoma cell line and in an ex vivo human placental perfusion model. The particles did not cause red cell haemolysis or blood clotting at concentrations up to 1 mM.
It was demonstrated herein that transport of MNPs across the placental barrier is highly dependent on particle size (cut off size of 200 nm PEGylated MNPs). Findings suggest the possibility of providing a safe method of iron chelation during pregnancy. Future work using in vivo models will be applied to study systemic particle interactions.
铁毒性是导致依赖输血的地中海贫血女性不良妊娠结局的主要因素。目前使用的铁螯合剂在孕期不被推荐，因为它们可穿过胎盘，对胎儿造成潜在风险。然而，停药无论在短期还是长期都可能对母亲健康产生不利影响。
我们之前证明黑色素纳米颗粒能有效螯合铁，这在铁过载小鼠中也得到了其他人的证实。本研究旨在评估这些纳米颗粒是否能穿过胎盘，并评估其生物相容性和血液相容性。
合成了50纳米、200纳米和500纳米的黑色素纳米颗粒文库，并用聚乙二醇（PEG）包被以提高其稳定性。对颗粒进行铁螯合功效和生物相容性测试。使用体外BeWo（绒毛膜癌）细胞模型和离体人胎盘灌注系统评估纳米颗粒的胎盘转运情况。
所有尺寸的黑色素纳米颗粒都能螯合铁，最大吸附量为每克材料14毫米铁；显著高于相同浓度的去铁胺（DFO）。还确定了尺寸合适（截止尺寸为200纳米）的聚乙二醇化黑色素纳米颗粒在使用人绒毛膜癌细胞系的体外模型和离体人胎盘灌注模型中可被限制穿过胎盘屏障。在浓度高达1毫摩尔时，这些颗粒不会导致红细胞溶血或血液凝固。
本文证明黑色素纳米颗粒穿过胎盘屏障的转运高度依赖颗粒大小（聚乙二醇化黑色素纳米颗粒的截止尺寸为200纳米）。研究结果表明在孕期提供一种安全的铁螯合方法具有可能性。未来将使用体内模型开展工作以研究全身颗粒相互作用。
