Nanoparticle Transport and Drug Delivery in Placental Systems

The placenta serves as the critical interface between maternal and foetal circulations, mediating nutrient transfer, gas exchange and hormonal signalling while restricting the passage of potentially harmful substances. Recent advances in nanotechnology promise to harness nanoparticle carriers to deliver therapeutics specifically to placental tissue, thereby treating disorders such as pre-eclampsia, foetal growth restriction or placenta-originated infections. The transplacental transport of nanoparticles depends on a combination of particle size, surface charge, hydrophobicity and functionalisation with targeting ligands. Small or neutrally charged particles may cross by passive diffusion or transcytosis, whereas larger or charged constructs often rely on receptor-mediated endocytosis or endovascular pathways. Surface engineering with polyethylene glycol, peptide motifs or placental chondroitin sulfate A-binding ligands can enhance retention within trophoblast layers and minimise foetal exposure. In addition, dynamic blood flow, placental architecture and gestational age influence biodistribution, while maternal immune mechanisms may clear or sequester nanoparticle formulations. Balancing efficient placental accumulation with minimal off-target effects in mother and foetus remains the central challenge. Integrating sensitive detection modalities, such as advanced imaging or perfusion models, and designing stimuli-responsive or degradable carriers are emerging strategies to optimise maternal-foetal safety and therapeutic efficacy.

Research from Nature Portfolio

Foundational investigations into the maternal-placental-foetal biodistribution of multimodal polymeric nanoparticles have elucidated the crucial influence of surface charge and gestational stage on tissue uptake. Using fluorescently labelled and magnetic poly(glycidyl methacrylate) particles with and without poly(ethyleneimine) coating, studies in pregnant rat models revealed preferential accumulation of cationic over anionic constructs within the placental chorionic plate at late gestation, while both variants were taken up by trophoblast giant cells at mid gestation. These findings demonstrate that subtle variations in nanoparticle chemistry can dramatically alter placental localisation and underscore the necessity for highly sensitive analytical methods when assessing maternal-foetal exposure in preclinical systems.

Nanoparticle Transport and Drug Delivery in Placental Systems publication trend

The graph below shows the total number of articles in nanoparticle transport and drug delivery in placental systems across all publications each year (not limited to Nature Index journals).

Technical terms

Nanoparticle: A particle with dimensions in the 1–100 nm range, often engineered for drug delivery.

Placenta: The organ that connects maternal and foetal blood supplies, facilitating exchange of substances.

Transplacental transport: The movement of molecules or particles across the placental barrier.

Biodistribution: The spatial distribution of a substance within an organism over time.

Homing peptide: A short amino acid sequence that directs a carrier to specific tissues or cell types.

Placental perfusion model: An ex vivo experimental system that mimics maternal-foetal circulation through human placental tissue.

Secretome: The complete set of secreted proteins and signalling molecules from a cell or tissue.

Chorionic plate: The foetal side of the placenta composed of trophoblast layers and vascular structures.

References

1. Maternal-placental-fetal biodistribution of multimodal polymeric nanoparticles in a pregnant rat model in mid and late gestation. Scientific Reports (2017).
2. Nanoparticles Dysregulate the Human Placental Secretome with Consequences on Angiogenesis and Vascularization. Advanced Science (2024).
3. Placental drug transport and fetal exposure during pregnancy is determined by drug molecular size, chemistry, and conformation. Journal of Controlled Release (2023).
4. Advance in placenta drug delivery: concern for placenta-originated disease therapy. Drug Delivery (2023).