{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:08:24Z","timestamp":1785431304640,"version":"3.56.0"},"reference-count":78,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford"},{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}]},{"name":"British Heart Foundation (BHF) Intermediate Fellowship","award":["FS\/IBSRF\/22\/25110"],"award-info":[{"award-number":["FS\/IBSRF\/22\/25110"]}]},{"award":["FS\/IBSRF\/22\/25110"],"award-info":[{"award-number":["FS\/IBSRF\/22\/25110"]}],"id":[{"id":"https:\/\/ror.org\/02wdwnk04","id-type":"ROR","asserted-by":"publisher"}]},{"name":"British Heart Foundation (BHF) Centre of Research Excellence, Oxford","award":["RE\/13\/1\/30181"],"award-info":[{"award-number":["RE\/13\/1\/30181"]}]},{"name":"British Heart Foundation (BHF) Centre of Research Excellence, Oxford","award":["RE\/18\/3\/34214"],"award-info":[{"award-number":["RE\/18\/3\/34214"]}]},{"name":"British Heart Foundation (BHF) Centre of Research Excellence, Oxford","award":["RE\/24\/130024"],"award-info":[{"award-number":["RE\/24\/130024"]}]},{"award":["RE\/13\/1\/30181"],"award-info":[{"award-number":["RE\/13\/1\/30181"]}],"id":[{"id":"https:\/\/ror.org\/02wdwnk04","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RE\/18\/3\/34214"],"award-info":[{"award-number":["RE\/18\/3\/34214"]}],"id":[{"id":"https:\/\/ror.org\/02wdwnk04","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RE\/24\/130024"],"award-info":[{"award-number":["RE\/24\/130024"]}],"id":[{"id":"https:\/\/ror.org\/02wdwnk04","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Nuffield Benefaction for Medicine"},{"name":"Wellcome Institutional Strategic Support Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/biom16050628","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:10:17Z","timestamp":1776939017000},"page":"628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Intracellular Delivery of Amino Acids to Trophoblast Cells Reveals Proteomic Signatures of Cellular Utilisation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4066-3011","authenticated-orcid":false,"given":"Emily","family":"Mazey","sequence":"first","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Flannery","sequence":"additional","affiliation":[{"name":"Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9715-5951","authenticated-orcid":false,"given":"Roman","family":"Fischer","sequence":"additional","affiliation":[{"name":"Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neva","family":"Kandzija","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4391-2523","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4637-5102","authenticated-orcid":false,"given":"Yuma","family":"Yamada","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4412-2144","authenticated-orcid":false,"given":"Manabu","family":"Tokeshi","sequence":"additional","affiliation":[{"name":"Faculty of Engineering, Hokkaido University, Sapporo 060-0813, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Errin","family":"Johnson","sequence":"additional","affiliation":[{"name":"Electron Microscopy Facility, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4620-6373","authenticated-orcid":false,"given":"Naveed","family":"Akbar","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Bancroft","sequence":"additional","affiliation":[{"name":"Cellular Imaging Core Facility, Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2975-5170","authenticated-orcid":false,"given":"Fadil M.","family":"Hannan","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6012-2574","authenticated-orcid":false,"given":"Manu","family":"Vatish","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","first-page":"401","article-title":"Placental Transport of Nutrients and Its Implications for Fetal Growth","volume":"54","author":"Bell","year":"1999","journal-title":"J. Reprod. Fertil. Suppl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/bs.pmbts.2016.12.008","article-title":"Regulation of Placental Amino Acid Transport and Fetal Growth","volume":"145","author":"Vaughan","year":"2017","journal-title":"Mol. Biol. Transl. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5511","DOI":"10.1113\/JP274883","article-title":"A Systems Perspective on Placental Amino Acid Transport","volume":"596","author":"Cleal","year":"2018","journal-title":"J. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1203\/00006450-199710000-00016","article-title":"Association between the Activity of the System A Amino Acid Transporter in the Microvillous Plasma Membrane of the Human Placenta and Severity of Fetal Compromise in Intrauterine Growth Restriction","volume":"42","author":"Glazier","year":"1997","journal-title":"Pediatr. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5427","DOI":"10.1210\/jcem.86.11.8036","article-title":"Placental Transport of Leucine, Phenylalanine, Glycine, and Proline in Intrauterine Growth-Restricted Pregnancies","volume":"86","author":"Paolini","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rosario, F.J., Kramer, A., Li, C., Galan, H.L., Powell, T.L., Nathanielsz, P.W., and Jansson, T. (2021). Reduction of In Vivo Placental Amino Acid Transport Precedes the Development of Intrauterine Growth Restriction in the Non-Human Primate. Nutrients, 13.","DOI":"10.3390\/nu13082892"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e14157","DOI":"10.1111\/apha.14157","article-title":"Regulation of Placental Amino Acid Transport in Health and Disease","volume":"240","author":"Shimada","year":"2024","journal-title":"Acta Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1159\/000299924","article-title":"Comparison of Uteroplacental Blood Flow in Normal and in Intrauterine Growth-Retarded Pregnancy","volume":"10","author":"Lunell","year":"1979","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1111\/j.1471-0528.1986.tb07830.x","article-title":"Inadequate Maternal Vascular Response to Placentation in Pregnancies Complicated by Pre-Eclampsia and by Small-for-Gestational Age Infants","volume":"93","author":"Khong","year":"1986","journal-title":"BJOG"},{"key":"ref_10","first-page":"895","article-title":"Fetal Blood Flow in Pregnancies Complicated by Intrauterine Growth Retardation","volume":"69","author":"Laurin","year":"1987","journal-title":"Obstet. Gynecol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1016\/S0301-2115(03)00173-8","article-title":"Uterine Blood Flow\u2014A Determinant of Fetal Growth","volume":"110","author":"Lang","year":"2003","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s12291-014-0450-4","article-title":"Effect of L-Arginine on Nitric Oxide Levels in Intrauterine Growth Restriction and Its Correlation with Fetal Outcome","volume":"30","author":"Singh","year":"2015","journal-title":"Indian J. Clin. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"532","DOI":"10.3945\/jn.115.221267","article-title":"L-Citrulline Supplementation Enhances Fetal Growth and Protein Synthesis in Rats with Intrauterine Growth Restriction","volume":"146","author":"Bourdon","year":"2016","journal-title":"J. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1007\/s00726-018-2608-5","article-title":"Maternal L-Glutamine Supplementation during Late Gestation Alleviates Intrauterine Growth Restriction-Induced Intestinal Dysfunction in Piglets","volume":"50","author":"Zhu","year":"2018","journal-title":"Amino Acids"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1093\/biolre\/ioy240","article-title":"Maternal L-Proline Supplementation Enhances Fetal Survival, Placental Development, and Nutrient Transport in Mice","volume":"100","author":"Liu","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Terstappen, F., Tol, A.J.C., Gremmels, H., Wever, K.E., Paauw, N.D., Joles, J.A., van der Beek, E.M., and Lely, A.T. (2020). Prenatal Amino Acid Supplementation to Improve Fetal Growth: A Systematic Review and Meta-Analysis. Nutrients, 12.","DOI":"10.3390\/nu12092535"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3736","DOI":"10.1016\/j.clnu.2020.03.036","article-title":"Maternal Supplementation with Citrulline or Arginine during Gestation Impacts Fetal Amino Acid Availability in a Model of Intrauterine Growth Restriction (IUGR)","volume":"39","author":"Bourdon","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.clnu.2022.05.014","article-title":"L-Arginine Supplementation Improved Neonatal Outcomes in Pregnancies with Hypertensive Disorder or Intrauterine Growth Restriction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"41","author":"Xu","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_19","first-page":"e14157","article-title":"Nanomedicine Review: Clinical Developments in Liposomal Applications","volume":"10","year":"2019","journal-title":"Cancer Nanotechnol."},{"key":"ref_20","first-page":"133","article-title":"Drug Delivery and Nanoparticles: Applications and Hazards","volume":"3","author":"Borm","year":"2008","journal-title":"Int. J. Nanomed."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1080\/17425247.2017.1276560","article-title":"Clinical Experience with Drug Delivery Systems as Tools to Decrease the Toxicity of Anticancer Chemotherapeutic Agents","volume":"14","author":"Vital","year":"2017","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bulbake, U., Doppalapudi, S., Kommineni, N., and Khan, W. (2017). Liposomal Formulations in Clinical Use: An Updated Review. Pharmaceutics, 9.","DOI":"10.3390\/pharmaceutics9020012"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liu, P., Chen, G., and Zhang, J. (2022). A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives. Molecules, 27.","DOI":"10.3390\/molecules27041372"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nrd1632","article-title":"Recent Advances with Liposomes as Pharmaceutical Carriers","volume":"4","author":"Torchilin","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1016\/j.addr.2008.08.005","article-title":"Active Targeting Schemes for Nanoparticle Systems in Cancer Therapeutics","volume":"60","author":"Byrne","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering Precision Nanoparticles for Drug Delivery","volume":"20","author":"Mitchell","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/1475-2875-7-104","article-title":"Identification of Glycosaminoglycan Binding Regions in the Plasmodium Falciparum Encoded Placental Sequestration Ligand, VAR2CSA","volume":"7","author":"Resende","year":"2008","journal-title":"Malar. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1126\/science.272.5267.1502","article-title":"Adherence of Plasmodium Falciparum to Chondroitin Sulfate A in the Human Placenta","volume":"272","author":"Fried","year":"1996","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.exppara.2005.12.003","article-title":"Plasmodium Falciparum: Chondroitin Sulfate A Is the Major Receptor for Adhesion of Parasitized Erythrocytes in the Placenta","volume":"113","author":"Fried","year":"2006","journal-title":"Exp. Parasitol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.7150\/thno.22904","article-title":"Placenta-Specific Drug Delivery by Trophoblast-Targeted Nanoparticles in Mice","volume":"8","author":"Zhang","year":"2018","journal-title":"Theranostics"},{"key":"ref_31","first-page":"1231","article-title":"The Establishment of a Cell Line of Human Hormone-Synthesizing Trophoblastic Cells in Vitro","volume":"28","author":"Pattillo","year":"1968","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1053\/plac.2000.0507","article-title":"Transport of Large Neutral Amino Acids into BeWo Cells","volume":"21","author":"Eaton","year":"2000","journal-title":"Placenta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1095\/biolreprod.110.085738","article-title":"Select Nutrients in the Ovine Uterine Lumen. VII. Effects of Arginine, Leucine, Glutamine, and Glucose on Trophectoderm Cell Signaling, Proliferation, and Migration","volume":"84","author":"Kim","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.jnutbio.2011.06.012","article-title":"L-Arginine Stimulates the MTOR Signaling Pathway and Protein Synthesis in Porcine Trophectoderm Cells","volume":"23","author":"Kong","year":"2012","journal-title":"J. Nutr. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1095\/biolreprod.112.105080","article-title":"Arginine, Leucine, and Glutamine Stimulate Proliferation of Porcine Trophectoderm Cells Through the MTOR-RPS6K-RPS6-EIF4EBP1 Signal Transduction Pathway","volume":"88","author":"Kim","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.placenta.2011.06.025","article-title":"Role of Nitric Oxide in Placental Vascular Development and Function","volume":"32","author":"Krause","year":"2011","journal-title":"Placenta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1161\/01.RES.0000027813.55750.E7","article-title":"Intrauterine Growth Retardation Is Associated With Reduced Activity and Expression of the Cationic Amino Acid Transport Systems Y+\/HCAT-1 and y +\/HCAT-2B and Lower Activity of Nitric Oxide Synthase in Human Umbilical Vein Endothelial Cells","volume":"91","author":"Casanello","year":"2002","journal-title":"Circ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1161\/01.HYP.0000116220.39793.c9","article-title":"L-Arginine Depletion in Preeclampsia Orients Nitric Oxide Synthase Toward Oxidant Species","volume":"43","author":"Noris","year":"2004","journal-title":"Hypertension"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1203\/00006450-200102000-00004","article-title":"Amino Acid Interconversions in the Fetal-Placental Unit: The Animal Model and Human Studies In Vivo","volume":"49","author":"Cetin","year":"2001","journal-title":"Pediatr. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.7150\/ijbs.45586","article-title":"Collagen at the Maternal-Fetal Interface in Human Pregnancy","volume":"16","author":"Shi","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1203\/00006450-199810000-00011","article-title":"Placental Transport of Leucine and Lysine Is Reduced in Intrauterine Growth Restriction","volume":"44","author":"Jansson","year":"1998","journal-title":"Pediatr. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1074\/mcp.T400003-MCP200","article-title":"Trypsin Cleaves Exclusively C-Terminal to Arginine and Lysine Residues","volume":"3","author":"Olsen","year":"2004","journal-title":"Mol. Cell. Proteom."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16.1.1","DOI":"10.1002\/0471140864.ps1601s62","article-title":"Overview of Peptide and Protein Analysis by Mass Spectrometry","volume":"62","author":"Zhang","year":"2010","journal-title":"Curr. Protoc. Protein Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1074\/mcp.M200025-MCP200","article-title":"Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics","volume":"1","author":"Ong","year":"2002","journal-title":"Mol. Cell. Proteom."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature19949","article-title":"Mass-Spectrometric Exploration of Proteome Structure and Function","volume":"537","author":"Aebersold","year":"2016","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1038\/nprot.2006.427","article-title":"A Practical Recipe for Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)","volume":"1","author":"Ong","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.1016\/j.xphs.2019.04.001","article-title":"The Use of a Microfluidic Device to Encapsulate a Poorly Water-Soluble Drug CoQ10 in Lipid Nanoparticles and an Attempt to Regulate Intracellular Trafficking to Reach Mitochondria","volume":"108","author":"Hibino","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1002\/jex2.66","article-title":"Oxford Acute Myocardial Infarction Study (OxAMI); et al. Comparative and Integrated Analysis of Plasma Extracellular Vesicle Isolation Methods in Healthy Volunteers and Patients Following Myocardial Infarction","volume":"1","author":"Paget","year":"2022","journal-title":"J. Extracell. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.1074\/jbc.M503202200","article-title":"High Density of Octaarginine Stimulates Macropinocytosis Leading to Efficient Intracellular Trafficking for Gene Expression","volume":"281","author":"Khalil","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/nar\/gkg034","article-title":"STRING: A Database of Predicted Functional Associations between Proteins","volume":"31","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"557","DOI":"10.2147\/IJN.S14615","article-title":"AFM, ESEM, TEM, and CLSM in Liposomal Characterization: A Comparative Study","volume":"6","author":"Ruozi","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Malenica, M., Vukomanovi\u0107, M., Kurtjak, M., Masciotti, V., dal Zilio, S., Greco, S., Lazzarino, M., Kru\u0161i\u0107, V., Per\u010di\u0107, M., and Jelovica Badovinac, I. (2021). Perspectives of Microscopy Methods for Morphology Characterisation of Extracellular Vesicles from Human Biofluids. Biomedicines, 9.","DOI":"10.3390\/biomedicines9060603"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e09394","DOI":"10.1016\/j.heliyon.2022.e09394","article-title":"Liposomes: Structure, Composition, Types, and Clinical Applications","volume":"8","author":"Nsairat","year":"2022","journal-title":"Heliyon"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13313","DOI":"10.3390\/molecules200713313","article-title":"Cell-Penetrating Peptides: Possibilities and Challenges for Drug Delivery in Vitro and in Vivo","volume":"20","author":"Skotland","year":"2015","journal-title":"Molecules"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1034\/j.1399-3011.2000.00723.x","article-title":"Polyarginine Enters Cells More Efficiently than Other Polycationic Homopolymers","volume":"56","author":"Mitchell","year":"2000","journal-title":"J. Pept. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s12668-022-00941-x","article-title":"A Comprehensive Review on Novel Liposomal Methodologies, Commercial Formulations, Clinical Trials and Patents","volume":"12","author":"Andra","year":"2022","journal-title":"Bionanoscience"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ong, S., Ming, L., Lee, K., and Yuen, K. (2016). Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes. Pharmaceutics, 8.","DOI":"10.3390\/pharmaceutics8030025"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.colsurfb.2014.09.029","article-title":"Liposomes as Carriers of Hydrophilic Small Molecule Drugs: Strategies to Enhance Encapsulation and Delivery","volume":"123","author":"Eloy","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.colsurfb.2008.02.001","article-title":"Membrane Interactions of Ternary Phospholipid\/Cholesterol Bilayers and Encapsulation Efficiencies of a RIP II Protein","volume":"64","author":"Manojlovic","year":"2008","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/btm2.10003","article-title":"Nanoparticles in the Clinic","volume":"1","author":"Anselmo","year":"2016","journal-title":"Bioeng. Transl. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/nrm729","article-title":"The Vacuolar (H+)-ATPases\u2014Nature\u2019s Most Versatile Proton Pumps","volume":"3","author":"Nishi","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"C1443","DOI":"10.1152\/ajpcell.00407.2003","article-title":"Vacuolar H+-ATPase in Human Breast Cancer Cells with Distinct Metastatic Potential: Distribution and Functional Activity","volume":"286","author":"Sennoune","year":"2004","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17514","DOI":"10.18632\/oncotarget.4239","article-title":"The Vacuolar H+ ATPase Is a Novel Therapeutic Target for Glioblastoma","volume":"6","author":"Ferrero","year":"2015","journal-title":"Oncotarget"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Singh, N., and Ecker, G. (2018). Insights into the Structure, Function, and Ligand Discovery of the Large Neutral Amino Acid Transporter 1, LAT1. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051278"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"892","DOI":"10.21037\/atm-21-2247","article-title":"SLC7A5 Serves as a Prognostic Factor of Breast Cancer and Promotes Cell Proliferation through Activating AKT\/MTORC1 Signaling Pathway","volume":"9","author":"Li","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e10866","DOI":"10.1016\/j.heliyon.2022.e10866","article-title":"SLC7A5 Is a Lung Adenocarcinoma-Specific Prognostic Biomarker and Participates in Forming Immunosuppressive Tumor Microenvironment","volume":"8","author":"Liu","year":"2022","journal-title":"Heliyon"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.cell.2008.11.044","article-title":"Bidirectional Transport of Amino Acids Regulates MTOR and Autophagy","volume":"136","author":"Nicklin","year":"2009","journal-title":"Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4161\/rna.21966","article-title":"The DEAD-Box Helicase EIF4A","volume":"10","author":"Andreou","year":"2013","journal-title":"RNA Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1007\/s00439-016-1683-5","article-title":"The HnRNP Family: Insights into Their Role in Health and Disease","volume":"135","author":"Geuens","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Hoter, A., El-Sabban, M., and Naim, H. (2018). The HSP90 Family: Structure, Regulation, Function, and Implications in Health and Disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092560"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (2008). How Cells Read the Genome: From DNA to Protein. Molecular Biology of the Cell, Garland Science.","DOI":"10.1201\/9780203833445"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"451","DOI":"10.2353\/ajpath.2008.071193","article-title":"Evidence of Placental Translation Inhibition and Endoplasmic Reticulum Stress in the Etiology of Human Intrauterine Growth Restriction","volume":"173","author":"Yung","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1440-1681.2008.05123.x","article-title":"Role of L-Arginine in Nitric Oxide Production in Health and Hypertension","volume":"36","author":"Rajapakse","year":"2009","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/BF00318873","article-title":"Physiological Dilation of Uteroplacental Arteries in the Guinea Pig Depends on Nitric Oxide Synthase Activity of Extravillous Trophoblast","volume":"282","author":"Nanaev","year":"1995","journal-title":"Cell Tissue Res."},{"key":"ref_75","unstructured":"Lopez, M.J., and Mohiuddin, S.S. (2023). Biochemistry, Essential Amino Acids, StatPearls."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/0300-9084(94)90076-0","article-title":"Translational Control during Amino Acid Starvation","volume":"76","author":"Pain","year":"1994","journal-title":"Biochimie"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1017\/S0029665199000828","article-title":"Amino Acid Limitation Regulates Gene Expression","volume":"58","author":"Bruhat","year":"1999","journal-title":"Proc. Nutr. Soc."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/s41392-023-01569-3","article-title":"Amino Acid Metabolism in Health and Disease","volume":"8","author":"Ling","year":"2023","journal-title":"Signal Transduct. Target. Ther."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/628\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:27:47Z","timestamp":1776940067000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":78,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["biom16050628"],"URL":"https:\/\/doi.org\/10.3390\/biom16050628","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]}}}