Tumor-homing peptides as tools for targeted delivery of payloads to the placenta.
Tumor-homing peptides as tools for targeted delivery of payloads to the placenta.
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DOI：
10.1126/sciadv.1600349
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发表时间：
2016-05
期刊：
影响因子：
13.6
通讯作者：
Harris LK
中科院分区：
文献类型：
--
作者：
King A;Ndifon C;Lui S;Widdows K;Kotamraju VR;Agemy L;Teesalu T;Glazier JD;Cellesi F;Tirelli N;Aplin JD;Ruoslahti E;Harris LK
肿瘤归巢肽已被用于制造靶向递送治疗药物到胎盘的纳米载体。治疗妊娠并发症的药物严重缺乏，主要是因为有对胎儿造成伤害的风险。在动物模型中，由于胎盘生长和功能的增强可以缓解母体症状并改善胎儿生长，我们开发了一种靶向向胎盘输送有效载荷的方法。我们发现肿瘤归巢肽序列CGKRK和iRGD选择性地结合到人类和小鼠的胎盘表面，并且不干扰正常发育。经静脉注射到怀孕小鼠体内的肽包被纳米颗粒在小鼠胎盘内积累，而对照纳米颗粒的结合和/或胎儿转移减少。我们使用靶向脂质体将羧基荧光素和胰岛素样生长因子2有效地输送到小鼠胎盘；后者显著增加了健康动物的平均胎盘重量，并显著改善了胎儿生长受限模型中胎儿的体重分布。这些数据为靶向给药到胎盘的原理提供了证据，并为胎盘特异性治疗的开发提供了一个新的平台。
Tumor-homing peptides have been exploited to create nanocarriers for targeted delivery of therapeutic agents to the placenta. The availability of therapeutics to treat pregnancy complications is severely lacking mainly because of the risk of causing harm to the fetus. As enhancement of placental growth and function can alleviate maternal symptoms and improve fetal growth in animal models, we have developed a method for targeted delivery of payloads to the placenta. We show that the tumor-homing peptide sequences CGKRK and iRGD bind selectively to the placental surface of humans and mice and do not interfere with normal development. Peptide-coated nanoparticles intravenously injected into pregnant mice accumulated within the mouse placenta, whereas control nanoparticles exhibited reduced binding and/or fetal transfer. We used targeted liposomes to efficiently deliver cargoes of carboxyfluorescein and insulin-like growth factor 2 to the mouse placenta; the latter significantly increased mean placental weight when administered to healthy animals and significantly improved fetal weight distribution in a well-characterized model of fetal growth restriction. These data provide proof of principle for targeted delivery of drugs to the placenta and provide a novel platform for the development of placenta-specific therapeutics.