{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:29:37Z","timestamp":1788791377748,"version":"build-2803163510"},"reference-count":74,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["AP23490945"],"award-info":[{"award-number":["AP23490945"]}]},{"award":["AP23490945"],"award-info":[{"award-number":["AP23490945"]}],"id":[{"id":"https:\/\/ror.org\/05tyne317","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012632","name":"Nazarbayev University","doi-asserted-by":"publisher","award":["211123CRP1614"],"award-info":[{"award-number":["211123CRP1614"]}],"id":[{"id":"10.13039\/501100012632","id-type":"DOI","asserted-by":"publisher"}]},{"award":["211123CRP1614"],"award-info":[{"award-number":["211123CRP1614"]}],"id":[{"id":"https:\/\/ror.org\/052bx8q98","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Liver-targeted drug delivery offers opportunities to increase therapeutic exposure at sites of hepatic disease while limiting systemic toxicity; however, successful targeting requires more than preferential accumulation of a carrier within the liver. This narrative review critically summarizes recent advances in synthetic, biological, and biomimetic delivery platforms, including lipid, polymeric, inorganic, and protein-based nanoparticles, nucleic acid nanocarriers, extracellular vesicles, plant-derived nanovesicles, cell-mediated systems, and cell membrane-coated nanoparticles. A literature search was conducted using PubMed, Web of Science, and Embase, with emphasis on studies published during the last decade and updated through 24 August 2026. Particular attention is given to the biological determinants of hepatic biodistribution, including sinusoidal architecture, physicochemical carrier properties, protein corona formation, receptor\u2013ligand interactions, and disease-associated alterations in the hepatic microenvironment. The review distinguishes organ-level hepatic accumulation from cell-specific uptake and productive intracellular delivery and discusses strategies directed toward hepatocytes, hepatic stellate cells, Kupffer cells and other macrophages, liver sinusoidal endothelial cells, neutrophils, and additional immune-cell populations. Major delivery platforms are critically compared with respect to the evidence supporting targeting specificity, cargo compatibility, administration route, reported safety and immunogenicity, manufacturability, analytical characterization, and translational maturity. Particular consideration is given to extracellular vesicle- and plant-derived nanovesicle-based approaches, for which biological activity, biodistribution, standardization, and scalability remain important areas of investigation. Overall, current research in liver-targeted delivery is increasingly focused on moving beyond nonspecific organ accumulation toward disease-adapted, cell-specific, and intracellularly productive delivery, although substantial biological, manufacturing, and regulatory challenges remain before many emerging approaches can achieve routine clinical translation.<\/jats:p>","DOI":"10.3390\/ijms27177959","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"7959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Current Advances in Liver-Targeted Drug Delivery: Synthetic, Biological, and Biomimetic Platforms"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6030-620X","authenticated-orcid":false,"given":"Shynggys","family":"Sergazy","sequence":"first","affiliation":[{"name":"LLP VICTUS PHARM, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roza B.","family":"Seidakhmetova","sequence":"additional","affiliation":[{"name":"LLP VICTUS PHARM, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6351-7756","authenticated-orcid":false,"given":"Yernur","family":"Zakirov","sequence":"additional","affiliation":[{"name":"Private Institution \u201cNational Laboratory Astana\u201d, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5266-3655","authenticated-orcid":false,"given":"Askhat","family":"Zhilkaidarov","sequence":"additional","affiliation":[{"name":"Private Institution \u201cNational Laboratory Astana\u201d, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damirzhan","family":"Amirbek","sequence":"additional","affiliation":[{"name":"LLP VICTUS PHARM, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8148-0816","authenticated-orcid":false,"given":"Zarina","family":"Shulgau","sequence":"additional","affiliation":[{"name":"LLP VICTUS PHARM, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6371-9210","authenticated-orcid":false,"given":"Kulzhan","family":"Berikkhanova","sequence":"additional","affiliation":[{"name":"Private Institution \u201cNational Laboratory Astana\u201d, Nazarbayev University, Astana 010000, Kazakhstan"},{"name":"University Medical Center, Nazarbayev University, Astana 010000, Kazakhstan"},{"name":"Professor G.V. Tsoi Scientific and Educational Center of Surgery, Astana Medical University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandr","family":"Gulyaev","sequence":"additional","affiliation":[{"name":"LLP VICTUS PHARM, Astana 010000, Kazakhstan"},{"name":"Private Institution \u201cNational Laboratory Astana\u201d, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41392-024-02072-z","article-title":"Liver diseases: Epidemiology, causes, trends and predictions","volume":"10","author":"Gan","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"300","DOI":"10.31729\/jnma.8124","article-title":"Spontaneous Bacterial Peritonitis among Chronic Liver Disease Patients with Ascites Admitted to the Department of Medicine of a Tertiary Care Centre: A Descriptive Cross-sectional Study","volume":"61","author":"Mahato","year":"2023","journal-title":"J. Nepal Med. Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Peng, M., Fang, F., and Wang, B. (2025). Nanoparticle technologies for liver targeting and their applications in liver diseases. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1661872"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41578-022-00529-7","article-title":"Passive, active and endogenous organ-targeted lipid and polymer nanoparticles for delivery of genetic drugs","volume":"8","author":"Dilliard","year":"2023","journal-title":"Nat. Rev. Mater."},{"key":"ref_6","first-page":"79","article-title":"Lipid-based nanoparticle technologies for liver targeting","volume":"154\u2013155","author":"Pauli","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5280","DOI":"10.3748\/wjg.v28.i36.5280","article-title":"Liver-specific drug delivery platforms: Applications for the treatment of alcohol-associated liver disease","volume":"28","author":"Warner","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"116702","DOI":"10.1016\/j.biopha.2024.116702","article-title":"Targeted delivery strategies: The interactions and applications of nanoparticles in liver diseases","volume":"175","author":"Meng","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"114238","DOI":"10.1016\/j.addr.2022.114238","article-title":"Why nanoparticles prefer liver macrophage cell uptake in vivo","volume":"185","author":"Ngo","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1038\/nmat4718","article-title":"Mechanism of hard-nanomaterial clearance by the liver","volume":"15","author":"Tsoi","year":"2016","journal-title":"Nat. Mater."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1111\/bcp.15990","article-title":"Effect of changes in metabolic enzymes and transporters on drug metabolism in the context of liver disease: Impact on pharmacokinetics and drug\u2013drug interactions","volume":"90","author":"Armani","year":"2024","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1039\/D3TB02790B","article-title":"Liver fibrosis: Pathological features, clinical treatment and application of therapeutic nanoagents","volume":"12","author":"Chen","year":"2024","journal-title":"J. Mater. Chem. B"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14029","DOI":"10.1021\/acsnano.2c03858","article-title":"Sequential Nano-Penetrators of Capillarized Liver Sinusoids and Extracellular Matrix Barriers for Liver Fibrosis Therapy","volume":"16","author":"Zhang","year":"2022","journal-title":"ACS Nano"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e2212206","DOI":"10.1002\/adma.202212206","article-title":"Restoration of Sinusoid Fenestrae Followed by Targeted Nanoassembly Delivery of an Anti-Fibrotic Agent Improves Treatment Efficacy in Liver Fibrosis","volume":"35","author":"Li","year":"2023","journal-title":"Adv. Mater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jconrel.2015.02.022","article-title":"Asialoglycoprotein receptor mediated hepatocyte targeting\u2014Strategies and applications","volume":"203","author":"Devarajan","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.addr.2017.05.007","article-title":"Hepatic stellate cells as key target in liver fibrosis","volume":"121","author":"Higashi","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1002\/hep.27376","article-title":"Liver sinusoidal endothelial cells in hepatic fibrosis","volume":"61","author":"DeLeve","year":"2015","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kaps, L., Leber, N., Klefenz, A., Choteschovsky, N., Zentel, R., Nuhn, L., and Schuppan, D. (2020). In Vivo siRNA Delivery to Immunosuppressive Liver Macrophages by \u03b1-Mannosyl-Functionalized Cationic Nanohydrogel Particles. Cells, 9.","DOI":"10.3390\/cells9081905"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Miettinen, H.M., Gripentrog, J.M., Lord, C.I., and Nagy, J.O. (2018). CD177-mediated nanoparticle targeting of human and mouse neutrophils. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200444"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1038\/s41467-022-31882-4","article-title":"Nanoparticle elasticity affects systemic circulation lifetime by modulating adsorption of apolipoprotein A-I in corona formation","volume":"13","author":"Li","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13651","DOI":"10.1039\/C7NR04685E","article-title":"A comparison of human and mouse protein corona profiles of functionalized SiO2 nanocarriers","volume":"9","author":"Chagolla","year":"2017","journal-title":"Nanoscale"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1021\/acsmaterialsau.3c00032","article-title":"Lipid-Based Nanoparticles for Drug\/Gene Delivery: An Overview of the Production Techniques and Difficulties Encountered in Their Industrial Development","volume":"3","author":"Mehta","year":"2023","journal-title":"ACS Mater. Au"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8698","DOI":"10.1021\/acs.jpcb.5b02891","article-title":"Microfluidic Mixing: A General Method for Encapsulating Macromolecules in Lipid Nanoparticle Systems","volume":"119","author":"Leung","year":"2015","journal-title":"J. Phys. Chem. B"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1038\/s41467-020-16248-y","article-title":"Synergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver","volume":"11","author":"Miao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1807748","DOI":"10.1002\/adma.201807748","article-title":"Nanoparticles Containing Oxidized Cholesterol Deliver mRNA to the Liver Microenvironment at Clinically Relevant Doses","volume":"31","author":"Paunovska","year":"2019","journal-title":"Adv. Mater."},{"key":"ref_26","unstructured":"U.S. Food and Drug Administration (2026, September 01). ONPATTRO (Patisiran) Lipid Complex Injection, for Intravenous Use: Prescribing Information, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/210922s000lbl.pdf."},{"key":"ref_27","first-page":"100411","article-title":"Nanoparticle-based drug delivery systems: A promising approach for the treatment of liver fibrosis","volume":"10","author":"Chen","year":"2025","journal-title":"Int. J. Pharm. X"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s11671-023-03943-0","article-title":"Exploration of inorganic nanoparticles for revolutionary drug delivery applications: A critical review","volume":"18","author":"Unnikrishnan","year":"2023","journal-title":"Discov. Nano"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6945","DOI":"10.2147\/IJN.S467876","article-title":"Albumin Nanoparticle-Based Drug Delivery Systems","volume":"19","author":"Qu","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7747","DOI":"10.1021\/acsami.2c19269","article-title":"Albumin-Based Silibinin Nanocrystals Targeting Activated Hepatic Stellate Cells for Liver Fibrosis Therapy","volume":"15","author":"Luo","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"nwac006","DOI":"10.1093\/nsr\/nwac006","article-title":"Construction of nanocarriers based on nucleic acids and their applications in nanobiology delivery systems","volume":"9","author":"Guo","year":"2022","journal-title":"Natl. Sci. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/s41467-023-44061-w","article-title":"DNA mechanocapsules for programmable piconewton responsive drug delivery","volume":"15","author":"Velusamy","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2305826","DOI":"10.1002\/adma.202305826","article-title":"Multimodal Tetrahedral DNA Nanoplatform for Surprisingly Rapid and Significant Treatment of Acute Liver Failure","volume":"36","author":"Wei","year":"2024","journal-title":"Adv. Mater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"123510","DOI":"10.1016\/j.biomaterials.2025.123510","article-title":"Engineered exosomes for targeted microRNA delivery to reverse liver fibrosis","volume":"324","author":"Zhang","year":"2026","journal-title":"Biomaterials"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1007\/s11095-024-03757-4","article-title":"Quality and Safety Considerations for Therapeutic Products Based on Extracellular Vesicles","volume":"41","author":"Takakura","year":"2024","journal-title":"Pharm. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108832","DOI":"10.1016\/j.pharmthera.2025.108832","article-title":"Plant-derived nanovesicles and therapeutic application","volume":"269","author":"Jung","year":"2025","journal-title":"Pharmacol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"213592","DOI":"10.1016\/j.bioadv.2023.213592","article-title":"Garlic-derived exosome-like nanovesicles as a hepatoprotective agent alleviating acute liver failure by inhibiting CCR2\/CCR5 signaling and inflammation","volume":"154","author":"Zhao","year":"2023","journal-title":"Biomater. Adv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5361","DOI":"10.1039\/D4BM00812J","article-title":"Hemp sprout-derived exosome-like nanovesicles as hepatoprotective agents attenuate liver fibrosis","volume":"12","author":"Kim","year":"2024","journal-title":"Biomater. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e70088","DOI":"10.1002\/fsn3.70088","article-title":"Pomegranate-Derived Exosome-Like Nanovesicles Containing Ellagic Acid Alleviate Gut Leakage and Liver Injury in MASLD","volume":"13","author":"Kim","year":"2025","journal-title":"Food Sci. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12975","DOI":"10.2147\/IJN.S526819","article-title":"Honeysuckle-Derived Exosome-Like Nanovesicles Protect Against Acute Liver Failure by Modulating Gut Microbiota","volume":"20","author":"Li","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"119022","DOI":"10.1016\/j.foodres.2026.119022","article-title":"Orally engineered liver-targeted garlic exosome-like nanovesicles for astaxanthin precise delivery against alcoholic liver disease in mice","volume":"233","author":"Qu","year":"2026","journal-title":"Food Res. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e23451","DOI":"10.1016\/j.heliyon.2023.e23451","article-title":"Drug-loaded erythrocytes: Modern approaches for advanced drug delivery for clinical use","volume":"10","author":"Berikkhanova","year":"2024","journal-title":"Heliyon"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Biagiotti, S., Pirla, E., and Magnani, M. (2023). Drug transport by red blood cells. Front. Physiol., 14, Erratum in Front. Physiol. 2024, 15, 1454770.","DOI":"10.3389\/fphys.2023.1308632"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1126\/science.288.5473.2051","article-title":"Role of CD47 as a marker of self on red blood cells","volume":"288","author":"Oldenborg","year":"2000","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e1706245","DOI":"10.1002\/adma.201706245","article-title":"Neutrophil-Based Drug Delivery Systems","volume":"30","author":"Chu","year":"2018","journal-title":"Adv. Mater."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sergazy, S., Berikkhanova, K., Gulyayev, A., Shulgau, Z., Maikenova, A., Bilal, R., Terzic, M., Zhumadilov, Z., and Aljofan, M. (2025). Cell-Based Drug Delivery Systems: Innovative Drug Transporters for Targeted Therapy. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26178143"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.addr.2020.09.001","article-title":"Advances on erythrocyte-mimicking nanovehicles to overcome barriers in biological microenvironments","volume":"170","author":"Castro","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejpb.2022.01.004","article-title":"Biomimetic platelet membrane-coated nanoparticles for targeted therapy","volume":"172","author":"Han","year":"2022","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2200289","DOI":"10.1002\/smtd.202200289","article-title":"Macrophage Cell Membrane-Cloaked Nanoplatforms for Biomedical Applications","volume":"6","author":"Lopes","year":"2022","journal-title":"Small Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jconrel.2023.01.052","article-title":"Liver fibrosis therapy based on biomimetic nanoparticles which deplete activated hepatic stellate cells","volume":"355","author":"Xia","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e202300236","DOI":"10.1002\/cmdc.202300236","article-title":"Cell Penetrating Peptides: Classification, Mechanisms, Methods of Study, and Applications","volume":"18","author":"Gori","year":"2023","journal-title":"ChemMedChem"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1080\/1061186X.2024.2386416","article-title":"Liver-targeted delivery based on prodrug: Passive and active approaches","volume":"32","author":"Chen","year":"2024","journal-title":"J. Drug Target."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"El-Kafrawy, S.A., Elkafrawy, M.S., Azhar, E.I., Saeed, A., and Tabll, A.A. (2025). Antibody treatment of hepatocellular carcinoma: A review of current and emerging approaches. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1533874"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nbt1396","article-title":"Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone","volume":"26","author":"Sato","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7547","DOI":"10.1021\/acsnano.1c00988","article-title":"Treatment of Hepatic Fibrosis in Mice Based on Targeted Plasmonic Hyperthermia","volume":"15","author":"Ribera","year":"2021","journal-title":"ACS Nano"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1021\/acs.molpharmaceut.7b00709","article-title":"PPB Peptide-Mediated siRNA-Loaded Stable Nucleic Acid Lipid Nanoparticles on Targeting Therapy of Hepatic Fibrosis","volume":"15","author":"Jia","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4704","DOI":"10.1021\/acsnano.3c06107","article-title":"Antioxidative Hyaluronic Acid\u2013Bilirubin Nanomedicine Targeting Activated Hepatic Stellate Cells for Anti-Hepatic-Fibrosis Therapy","volume":"18","author":"Shinn","year":"2024","journal-title":"ACS Nano"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e2202228","DOI":"10.1002\/adhm.202202228","article-title":"CD44-Targeting Drug Delivery System of Exosomes Loading Forsythiaside a Combats Liver Fibrosis via Regulating NLRP3-Mediated Pyroptosis","volume":"12","author":"Gong","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.jconrel.2020.09.041","article-title":"Fibroblast growth factor 2 conjugated superparamagnetic iron oxide nanoparticles ameliorate hepatic stellate cells activation in vitro and acute liver injury in vivo","volume":"328","author":"Kurniawan","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"18324","DOI":"10.1038\/s41598-021-97808-0","article-title":"Asialoglycoprotein receptor targeted optical and magnetic resonance imaging and therapy of liver fibrosis using pullulan stabilized multi-functional iron oxide nanoprobe","volume":"11","author":"Saraswathy","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10717544.2017.1399301","article-title":"Enhanced efficacy of curcumin with phosphatidylserine-decorated nanoparticles in the treatment of hepatic fibrosis","volume":"25","author":"Wang","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12951-021-01205-8","article-title":"Nano delivery of simvastatin targets liver sinusoidal endothelial cells to remodel tumor microenvironment for hepatocellular carcinoma","volume":"20","author":"Yu","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s41565-021-01030-y","article-title":"Species-dependent in vivo mRNA delivery and cellular responses to nanoparticles","volume":"17","author":"Hatit","year":"2022","journal-title":"Nat. Nanotechnol."},{"key":"ref_65","unstructured":"U.S. Food and Drug Administration (2026, September 01). GIVLAARI (Givosiran) Injection, for Subcutaneous Use: Prescribing Information, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/212194s007lbl.pdf."},{"key":"ref_66","unstructured":"U.S. Food and Drug Administration (2026, September 01). OXLUMO (Lumasiran) Injection, for Subcutaneous Use: Prescribing Information, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/214103s006lbl.pdf."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1056\/NEJMoa2205416","article-title":"Fazirsiran for Liver Disease Associated with Alpha1-Antitrypsin Deficiency","volume":"387","author":"Strnad","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_68","unstructured":"(2026, September 01). ClinicalTrials.gov. NCT05677971. Study to Check the Safety of Fazirsiran and Learn if Fazirsiran Can Help People with Liver Disease and Scarring (Fibrosis) Due to an Abnormal Version of Alpha-1 Antitrypsin Protein. Phase 3; Recruitment Status: Recruiting; Last Update Posted 13 May 2026; Last Verified May 2026, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05677971."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"114569","DOI":"10.1016\/j.jconrel.2025.114569","article-title":"Hepatocyte-specific partial cellular reprogramming via selective OSK mRNA lipid nanoparticle attenuates liver fibrosis","volume":"390","author":"Zhang","year":"2026","journal-title":"J. Control. Release"},{"key":"ref_70","unstructured":"(2026, September 01). ClinicalTrials.gov. NCT07409259. PT-MSCs Exosome Injection in the Treatment of Chronic-to-Acute Liver Failure. Early Phase 1; Recruitment Status: Active, Not Recruiting, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07409259."},{"key":"ref_71","unstructured":"U.S. Food and Drug Administration (2026, September 01). Orphan Drug Designations and Approvals: Signal Regulatory Protein Alpha (SIRPalpha)-Exosome. Orphan Designation: Treatment of Acute Liver Failure Regardless of Etiology; Designation Date: 25 January 2024; Orphan Designation Status: Designated; FDA Orphan Approval Status: Not FDA Approved for Orphan Indication, Available online: https:\/\/www.accessdata.fda.gov\/scripts\/opdlisting\/oopd\/detailedIndex.cfm?cfgridkey=931123."},{"key":"ref_72","unstructured":"U.S. Food and Drug Administration (2026, September 01). Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation. Guidance for Industry, Available online: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/liposome-drug-products-chemistry-manufacturing-and-controls-human-pharmacokinetics-and."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e13904","DOI":"10.1111\/cts.13904","article-title":"Regulation of exosomes as biologic medicines: Regulatory challenges faced in exosome development and manufacturing processes","volume":"17","author":"Wang","year":"2024","journal-title":"Clin. Transl. Sci."},{"key":"ref_74","unstructured":"U.S. Food and Drug Administration (2026, September 01). R3 Medical Companies\u2014Warning Letter 726330, Available online: https:\/\/www.fda.gov\/inspections-compliance-enforcement-and-criminal-investigations\/warning-letters\/r3-medical-companies-726330-08142026."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7959\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:59:44Z","timestamp":1788789584000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":74,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177959"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177959","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]}}}