Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction.
Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction.
复制标题
DOI：
10.3390/pharmaceutics13111778
复制
发表时间：
2021-10-25
期刊：
影响因子：
5.4
通讯作者：
Harris LK
中科院分区：
文献类型：
--
作者：
Renshall LJ;Beards F;Evangelinos A;Greenwood SL;Brownbill P;Stevens A;Sibley CP;Aplin JD;Johnstone ED;Teesalu T;Harris LK
胎盘功能障碍是妊娠并发症如胎儿生长受限（FGR）和先兆子痫的根本原因。没有治疗功能不良的胎盘的疗法，主要是由于全身给药引起的母体和胎儿不良副作用的风险。使用靶向脂质体选择性地将有效载荷递送至胎盘具有克服这些问题的潜力。在这项研究中，我们评估了表皮生长因子（EGF）负载的肽修饰脂质体改善胎盘功能的不同方面的安全性和有效性，使用来自足月健康对照妊娠和FGR并发妊娠的组织。噬菌体筛选确定了肽序列，CGPSARAPC（GPS），它选择性地归巢到小鼠胎盘在体内，并结合到体外人胎盘外植体的外合胞体滋养层。制备含有PBS或EGF（50-100 ng/mL）的GPS修饰的脂质体，并将胎盘外植体与脂质体一起培养长达48 h。未修饰和GPS修饰的脂质体含有PBS不影响氨基酸转运的基础速率，人绒毛膜促性腺激素（hCG）释放或细胞周转在胎盘外植体从健康对照。含有EGF的GPS修饰的脂质体显著增加了健康对照外植体中的氨基酸转运体活性，但在FGR妇女的胎盘外植体中没有。hCG分泌和细胞周转率不受EGF递送的影响;然而，当EGF通过GPS修饰的脂质体与未修饰的脂质体递送时，观察到下游蛋白激酶的差异活化。这些数据表明，靶向脂质体是一种安全和有用的工具，用于开发胎盘功能障碍的新疗法，重现游离EGF的作用。
Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus resulting from systemic drug delivery. The use of targeted liposomes to selectively deliver payloads to the placenta has the potential to overcome these issues. In this study, we assessed the safety and efficacy of epidermal growth factor (EGF)-loaded, peptide-decorated liposomes to improve different aspects of placental function, using tissue from healthy control pregnancies at term, and pregnancies complicated by FGR. Phage screening identified a peptide sequence, CGPSARAPC (GPS), which selectively homed to mouse placentas in vivo, and bound to the outer syncytiotrophoblast layer of human placental explants ex vivo. GPS-decorated liposomes were prepared containing PBS or EGF (50–100 ng/mL), and placental explants were cultured with liposomes for up to 48 h. Undecorated and GPS-decorated liposomes containing PBS did not affect the basal rate of amino acid transport, human chorionic gonadotropin (hCG) release or cell turnover in placental explants from healthy controls. GPS-decorated liposomes containing EGF significantly increased amino acid transporter activity in healthy control explants, but not in placental explants from women with FGR. hCG secretion and cell turnover were unaffected by EGF delivery; however, differential activation of downstream protein kinases was observed when EGF was delivered via GPS-decorated vs. undecorated liposomes. These data indicate that targeted liposomes represent a safe and useful tool for the development of new therapies for placental dysfunction, recapitulating the effects of free EGF.
登录
查看更多内容
DOI：
10.1016/j.jconrel.2020.05.033
发表时间：
2020-08-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Alfaifi AA;Heyder RS;Bielski ER;Almuqbil RM;Kavdia M;Gerk PM;da Rocha SRP
通讯作者：
da Rocha SRP
影响因子：
7.2
作者：
Heazell, Alexander E. P.;Sharp, Andrew N.;Crocker, Ian P.
通讯作者：
Crocker, Ian P.
影响因子：
15.9
作者：
FONDACCI, C;ALSAT, E;EVAINBRION, D
通讯作者：
EVAINBRION, D
影响因子：
38.3
作者：
Hawkins, Simon J.;Crompton, Lucy A.;Caldwell, Maeve A.
通讯作者：
Caldwell, Maeve A.
影响因子：
7.2
作者：
Izutsu, T;Kudo, T;Nakagawara, K
通讯作者：
Nakagawara, K