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Biomolecules
Volume 16
Issue 5
10.3390/biom16050628
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Article

Targeted Intracellular Delivery of Amino Acids to Trophoblast Cells Reveals Proteomic Signatures of Cellular Utilisation

by
Emily Mazey
1,*,
Sarah Flannery
2,
Roman Fischer
2,
Neva Kandzija
1,
Wei Zhang
1,
Yuma Yamada
3,
Manabu Tokeshi
4,
Errin Johnson
5,
Naveed Akbar
6,
James Bancroft
7,
Fadil M. Hannan
1 and
Manu Vatish
1
1
Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK
2
Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK
3
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
4
Faculty of Engineering, Hokkaido University, Sapporo 060-0813, Japan
5
Electron Microscopy Facility, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
6
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK
7
Cellular Imaging Core Facility, Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
*
Author to whom correspondence should be addressed.
Biomolecules 2026, 16(5), 628; https://doi.org/10.3390/biom16050628
Submission received: 13 February 2026 / Revised: 9 April 2026 / Accepted: 17 April 2026 / Published: 23 April 2026
(This article belongs to the Section Cellular Biochemistry)
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Abstract

Targeted delivery systems offer a promising approach for selectively modulating cellular processes; yet the intracellular consequences of targeted nutrient delivery to trophoblast cells remain poorly defined. Here, we investigated a previously validated placenta-targeting peptide conjugated to liposomes encapsulating stable isotope-labelled L-arginine and L-lysine to examine cellular uptake and downstream molecular responses in a trophoblast-like cell model. Peptide-dependent uptake of fluorescently labelled liposomes was confirmed in BeWo cells, demonstrating selective internalisation compared with non-targeted controls. Encapsulation of isotope-labelled amino acids enabled direct quantification of intracellular delivery and incorporation into the cellular proteome using stable isotope labelling by amino acids in cell culture (SILAC). Quantitative proteomic analysis revealed coordinated changes in proteins associated with translation, metabolism, and nitric oxide synthase regulation following targeted liposomal uptake. Notably, V-type proton ATPase subunit G1 (ATP6V1G1) and large neutral amino acid transporter small subunit 1 (SLC7A5) showed increased incorporation of labelled amino acids and were independently validated by Western blotting. Together, these findings establish a proof-of-concept platform for targeted intracellular amino acid delivery to trophoblast-like cells and define the resulting proteomic responses. This work provides mechanistic insight into intracellular amino acid utilisation and a framework for future studies in placental cell biology.
Keywords: placenta-targeted delivery; liposomes; placental chondroitin sulfate-A-binding peptide (plCSA-bp); trophoblast cells; amino acid delivery; SILAC proteomics; quantitative proteomics placenta-targeted delivery; liposomes; placental chondroitin sulfate-A-binding peptide (plCSA-bp); trophoblast cells; amino acid delivery; SILAC proteomics; quantitative proteomics

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MDPI and ACS Style

Mazey, E.; Flannery, S.; Fischer, R.; Kandzija, N.; Zhang, W.; Yamada, Y.; Tokeshi, M.; Johnson, E.; Akbar, N.; Bancroft, J.; et al. Targeted Intracellular Delivery of Amino Acids to Trophoblast Cells Reveals Proteomic Signatures of Cellular Utilisation. Biomolecules 2026, 16, 628. https://doi.org/10.3390/biom16050628

AMA Style

Mazey E, Flannery S, Fischer R, Kandzija N, Zhang W, Yamada Y, Tokeshi M, Johnson E, Akbar N, Bancroft J, et al. Targeted Intracellular Delivery of Amino Acids to Trophoblast Cells Reveals Proteomic Signatures of Cellular Utilisation. Biomolecules. 2026; 16(5):628. https://doi.org/10.3390/biom16050628

Chicago/Turabian Style

Mazey, Emily, Sarah Flannery, Roman Fischer, Neva Kandzija, Wei Zhang, Yuma Yamada, Manabu Tokeshi, Errin Johnson, Naveed Akbar, James Bancroft, and et al. 2026. "Targeted Intracellular Delivery of Amino Acids to Trophoblast Cells Reveals Proteomic Signatures of Cellular Utilisation" Biomolecules 16, no. 5: 628. https://doi.org/10.3390/biom16050628

APA Style

Mazey, E., Flannery, S., Fischer, R., Kandzija, N., Zhang, W., Yamada, Y., Tokeshi, M., Johnson, E., Akbar, N., Bancroft, J., Hannan, F. M., & Vatish, M. (2026). Targeted Intracellular Delivery of Amino Acids to Trophoblast Cells Reveals Proteomic Signatures of Cellular Utilisation. Biomolecules, 16(5), 628. https://doi.org/10.3390/biom16050628

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