2. Academic Validation
  3. Placenta-specific drug delivery by trophoblast-targeted nanoparticles in mice

Placenta-specific drug delivery by trophoblast-targeted nanoparticles in mice

  • Theranostics. 2018 Apr 9;8(10):2765-2781. doi: 10.7150/thno.22904.
Baozhen Zhang 1,  Lunbo Tan 1 2,  Yan Yu 3,  Baobei Wang 1,  Zhilong Chen 1 2,  Jinyu Han 1,  Mengxia Li 1,  Jie Chen 1,  Tianxia Xiao 1,  Balamurali K Ambati 4,  Lintao Cai 5,  Qing Yang 2,  Nihar R Nayak 6,  Jian Zhang 1,  Xiujun Fan 1
Affiliations

Affiliations

  • 1 Laboratory for Reproductive Health, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, Guangdong, China, 518055.
  • 2 College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, China, 410128.
  • 3 Bao'an Maternal and Child Health Care Hospital, Shenzhen, China, 518133.
  • 4 John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA, 84132.
  • 5 Guangdong Key Laboratory of Nanomedicine, CAS Key Lab for Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China, 518055.
  • 6 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, C.S. Mott Center for Human Growth and Development, Detroit, Michigan, USA, 48201.
PMID: 29774074 DOI: 10.7150/thno.22904
Abstract

Rationale: The availability of therapeutics to treat pregnancy complications is severely lacking, mainly due to the risk of harm to the fetus. In placental malaria, Plasmodium falciparum-infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) on the surfaces of trophoblasts. Based on this principle, we have developed a method for targeted delivery of payloads to the placenta using a synthetic placental CSA-binding peptide (plCSA-BP) derived from VAR2CSA, a CSA-binding protein expressed on IEs. Methods: A biotinylated plCSA-BP was used to examine the specificity of plCSA-BP binding to mouse and human placental tissue in tissue sections in vitro. Different nanoparticles, including plCSA-BP-conjugated nanoparticles loaded with indocyanine green (plCSA-INPs) or methotrexate (plCSA-MNPs), were administered intravenously to pregnant mice to test their efficiency at drug delivery to the placenta in vivo. The tissue distribution and localization of the plCSA-INPs were monitored in live Animals using an IVIS imaging system. The effect of plCSA-MNPs on fetal and placental development and pregnancy outcome were examined using a small-animal high-frequency ultrasound (HFUS) imaging system, and the concentrations of methotrexate in fetal and placental tissues were measured using high-performance liquid chromatography (HPLC). Results: plCSA-BP binds specifically to trophoblasts and not to Other cell types in the placenta or to CSA-expressing cells in Other tissues. Moreover, we found that intravenously administered plCSA-INPs accumulate in the mouse placenta, and ex vivo analysis of the fetuses and placentas confirmed placenta-specific delivery of these nanoparticles. We also demonstrate successful delivery of methotrexate specifically to placental cells by plCSA-BP-conjugated nanoparticles, resulting in dramatic impairment of placental and fetal development. Importantly, plCSA-MNPs treatment had no apparent adverse effects on maternal tissues. Conclusion: These results demonstrate that plCSA-BP-guided nanoparticles could be used for the targeted delivery of payloads to the placenta and serve as a novel placenta-specific drug delivery option.

Keywords

chondroitin sulfate A; nanoparticles; placental CSA binding peptide; trophoblast.

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