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Nanoparticle-mediated delivery of placental gene therapy via uterine artery catheterization in a pregnant rhesus macaque.

作者信息

Schmidt Jenna K, Wilson Rebecca L, Davenport Baylea N, Hacker Timothy A, Fitz Casey, Simmons Heather A, Schotzko Michele L, Golos Thaddeus G, Jones Helen N

机构信息

Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA.

Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, USA; Center for Research in Perinatal Outcomes, College of Medicine, University of Florida, Gainesville, FL, USA.

出版信息

Placenta. 2024 Sep 20. doi: 10.1016/j.placenta.2024.09.013.


DOI:10.1016/j.placenta.2024.09.013
PMID:39362807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11947900/
Abstract

Nanoparticles offer promise as a mechanism to non-invasively deliver targeted placental therapeutics. Our previous studies utilizing intraplacental administration demonstrate efficient nanoparticle uptake into placental trophoblast cells and overexpression of human IGF1 (hIGF1). Nanoparticle-mediated placental overexpression of hIGF1 in small animal models of placental insufficiency and fetal growth restriction improved nutrient transport and restored fetal growth. The objective of this pilot study was to extend these studies to the pregnant nonhuman primate and develop a method for local delivery of nanoparticles to the placenta via maternal blood flow from the uterine artery. Nanoparticles containing hIGF1 plasmid driven by the placenta-specific PLAC1 promoter were delivered to a mid-gestation pregnant rhesus macaque via a catheterization approach that is clinically used for uterine artery embolization. Maternal-fetal interface, fetal and maternal tissues were collected four days post-treatment to evaluate the efficacy of hIGF1 treatment in the placenta. The uterine artery catheterization procedure and nanoparticle treatment was well tolerated by the dam and fetus through the four-day study period following catheterization. Nanoparticles were taken up by the placenta from maternal blood as plasmid-specific hIGF1 expression was detected in multiple regions of the placenta via in situ hybridization and qPCR. The uterine artery catheterization approach enabled successful delivery of nanoparticles to maternal circulation in close proximity to the placenta with no concerns to maternal or fetal health in this short-term feasibility study. In the future, this delivery approach can be used for preclinical evaluation of the long-term safety and efficacy of nanoparticle-mediated placental therapies in a rhesus macaque model.

摘要

相似文献

[1]
Nanoparticle-mediated delivery of placental gene therapy via uterine artery catheterization in a pregnant rhesus macaque.

Placenta. 2024-9-20

[2]
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[3]
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引用本文的文献

[1]
Therapeutic nanoparticle safety in pregnancy: Bridging knowledge gaps with environmental insights and a translational roadmap.

J Control Release. 2025-9-10

本文引用的文献

[1]
Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model.

PLoS Pathog. 2023-8

[2]
Rhesus macaque fetal and placental growth demographics: A resource for laboratory animal researchers.

Am J Primatol. 2023-8

[3]
Placental treatment with via nanoparticle differentially impacts vascular remodeling factors in guinea pig sub-placenta/decidua.

Front Physiol. 2023-1-4

[4]
Nanoparticle-mediated transgene expression of insulin-like growth factor 1 in the growth restricted guinea pig placenta increases placenta nutrient transporter expression and fetal glucose concentrations.

Mol Reprod Dev. 2022-11

[5]
Insulin-like growth factor 1 signaling in the placenta requires endothelial nitric oxide synthase to support trophoblast function and normal fetal growth.

Am J Physiol Regul Integr Comp Physiol. 2021-5-1

[6]
Nanoparticle mediated increased insulin-like growth factor 1 expression enhances human placenta syncytium function.

Placenta. 2020-4

[7]
Prenatal growth in the cynomolgus and rhesus macaque (Macaca fascicularis and Macaca mulatta): A comparison by ultrasonography.

Am J Primatol. 1988

[8]
Molecular actions of heparin and their implications in preventing pre-eclampsia.

J Thromb Haemost. 2018-6-7

[9]
Child neurodevelopmental outcomes following preterm and term birth: What can the placenta tell us?

Placenta. 2017-6-15

[10]
Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques.

PLoS Pathog. 2017-5-25

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