Info
Background:
Sensitive methods for tracking nanoplastic biodistribution during pregnancy remain limited, particularly for determining whether systemically circulating particles reach placental and embryo-associated compartments over time.[1,2] Prior human and experimental studies have raised concern that micro- and nanoplastics may access the placenta and, under some conditions, fetal tissues. PET/CT imaging with radiolabeled nanoparticles offers a noninvasive approach for longitudinal whole-body tracking and can be complemented by terminal biodistribution measurements.[3]

Hypothesis/Objective:
It was hypothesized that intravenously administered 89Zr-labeled polystyrene (PS) and polyvinyl chloride (PVC) nanoparticles would cross the placental barrier during late gestation and become detectable in placental and embryo-associated tissues. The objective was to determine whether a radiolabeling-enabled PET/CT and ex vivo biodistribution workflow could sensitively track maternal-fetal nanoplastic transfer and compare the biodistribution of similarly sized PS and PVC nanoparticles in pregnant mice.

Methods:
PS and PVC nanoparticles were functionalized with desferrioxamine (DFO) and subsequently radiolabeled with 89Zr. Commercially obtained spherical PS-NH2 nanoparticles were directly conjugated to DFO prior to radiolabeling, whereas non-spherical PVC nanoparticles were synthesized, aminated, and subsequently conjugated to DFO before radiolabeling. PET/CT imaging of pregnant mice (GD 13) was performed at 1, 6, 12, 24, 48, and 72 h after tail vein injection (100 µg of nanoplastic, 60 µCi in 100 µL PBS, n = 6). Tissues were collected on gestational day 17 (96 h post-injection) for gamma counting. Group comparisons were performed organ-by-organ using Welch’s unpaired t-tests.

Results:
Particle characterization by dynamic light scattering showed mean diameters of 224 ± 85 nm (PDI = 0.145) for PS and 209 ± 114 nm (PDI = 0.299) for PVC, with zeta potentials of -37.5 ± 0.4 mV and -29.6 ± 0.2 mV, respectively. PVC radiolabel stability remained over 95% up to 96 h in simulated lung fluid, simulated gastric fluid, serum, simulated intestinal fluid, and PBS. Stability of radiolabeled PS has been reported previously.[3,4] PET/CT demonstrated predominant liver and spleen signals for both materials throughout the imaging period. Ex vivo biodistribution at 96 h confirmed strong reticuloendothelial uptake and revealed polymer-dependent differences despite similar particle size. PVC showed significantly greater accumulation than PS in liver (31.07 vs 13.70 %ID/g, p = 0.0116), spleen (261.95 vs 17.05 %ID/g, p = 0.0142), and stomach (0.395 vs 0.097 %ID/g, p = 0.0111). In contrast, PS showed significantly greater uptake in kidneys (3.69 vs 2.11 %ID/g, p = 0.0002) and brain (0.126 vs 0.018 %ID/g, p = 0.0008). Reproductive tissue-associated activity was detected for both materials. Placenta-associated activity was 0.738 vs 0.685 %ID/g and ovarian activity was 0.180 vs 0.089 %ID/g for PVC and PS, respectively. There was no significant between-group differences in either tissue. Embryo-associated activity remained very low for both PVC and PS (0.0090 vs 0.0075 %ID/g).

Conclusion:
89Zr-labeled PS and PVC nanoparticles were detected in placental and embryo-associated tissues following intravenous administration during late gestation, supporting maternal-fetal translocation. Although embryo-associated signal remained low and was more readily detected ex vivo than by in vivo PET, the combined radiolabeling, PET/CT, and gamma-counting workflow successfully tracked nanoplastic trafficking during pregnancy. Both materials also showed strong hepatic and splenic retention, indicating polymer-dependent biodistribution alongside detectable reproductive tissue exposure.

Image/Figure:
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Image/Figure Caption:
Longitudinal PET/CT tracking of 89Zr-labeled polystyrene (PS) and polyvinyl chloride (PVC) nanoparticles in pregnant mice. Representative coronal PET/CT maximum-intensity projections acquired at 1, 6, 12, 24, 48, and 72 h after tail-vein administration of 89Zr-labeled PS or PVC nanoparticles to pregnant mice (GD13; n = 6; 100 µg nanoplastic, 60 µCi in 100 µL PBS). Insets summarize particle identity and hydrodynamic size. Both materials showed dominant signal in the liver and spleen over time, consistent with reticuloendothelial uptake.

Author
Olga Khaybullina
University of Alabama at Birmingham