The maternal-fetal transfer of passive immunity as a mechanism of transplacental nanoparticle drug delivery for prenatal therapies. (1st August 2022)

• Record Type: Journal Article
• Authors: Tse, Wai Hei; Higgins, Sean; Patel, Daywin; Xing, Malcolm; West, Adrian R.; Labouta, Hagar I.; Keijzer, Richard
• Is Part Of: Biomaterials science. Volume 10:Number 18(2022)
• Page Start: 5243
• Page End: 5253
• Publication Date: 2022-08-01
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d2bm00293k
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : Nanoparticles surface-modified with IgG isoform antibodies as a potential platform for the transplacental targeted delivery of therapeutics to the developing fetus. Abstract : Nanoparticles administered into the maternal circulation and across the placenta are a potential clinical therapy to treat congenital diseases. The mechanism by which nanoparticles can safely cross the placenta for targeted drug delivery to the fetus remains poorly understood. We demonstrate that the maternal-fetal transfer of passive immunity through the neonatal Fc Receptor (FcRn) can induce the transplacental transfer of chitosan nanoparticles modifed with IgG antibodies (414 ± 27 nm). The transfer of FITC-tagged IgG-modified chitosan nanoparticles was 2.8 times higher ( p = 0.0264) compared to similarly-sized unmodified chitosan nanoparticles (375 ± 17 nm). Co-administration of free IgG competitively diminished the transplacental transfer of IgG-modified nanoparticles, yet unmodified nanoparticles remained unaffected. Colocalization of the FcRn and the IgG-modified chitosan nanoparticles were observed with confocal microscopy. Barrier function before and after nanoparticle administration remained intact as determined by TEER (75–79 Ω cm 2 ) and immmunofluorescence of ZO-1 tight junction proteins. The results provide insight into the clinical applications of nanoparticles for prenatal therapies using the mechanism of the maternal-fetal transfer of passive immunity.