{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:59:56Z","timestamp":1792155596254,"version":"4.4.0"},"reference-count":78,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Cardiovascular diseases remain the leading cause of death worldwide and are often managed through invasive surgical procedures such as heart transplantation, ventricular assist device implantation, coronary artery bypass grafting, and stent placement. However, significant unmet medical needs persist in this field. The development of pharmaceutical agents using non-invasive delivery strategies is therefore of critical importance. Current treatments often target peripheral tissues or organs\u2014such as capillary endothelial cells, vascular smooth muscle, and renal tubules\u2014to reduce cardiac workload by lowering blood pressure. However, effective drug delivery directly to the myocardium continues to pose a significant challenge. For conditions such as congestive heart failure (CHF) and myocardial infarction (MI), targeted delivery of therapeutic agents to the heart is essential. In this perspective review, I discuss the potential and emerging strategies for non-invasive cardiac drug delivery, focusing on receptor-mediated endocytosis and transcytosis using nanoparticle-based delivery systems that have frequently been employed for targeting the brain or cancer cells although their use for cardiac delivery remains largely unexplored.<\/jats:p>","DOI":"10.3390\/pharmaceutics17111365","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:14:02Z","timestamp":1761182042000},"page":"1365","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Nanoparticle-Based Targeted Drug Delivery Methods for Heart-Specific Distribution in Cardiovascular Therapy"],"prefix":"10.3390","volume":"17","author":[{"given":"Toshihiko","family":"Tashima","sequence":"first","affiliation":[{"name":"Tashima Laboratories of Arts and Sciences, 1239-5 Toriyama-cho, Kohoku-ku, Yokohama 222-0035, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","unstructured":"The World Health Organization (2025, January 01). Cardiovascular Diseases. Available online: https:\/\/www.who.int\/health-topics\/cardiovascular-diseases#tab=tab_1."},{"key":"ref_2","unstructured":"The World Health Organization (2025, January 01). Cardiovascular Diseases (CVDs). 11 June 2021. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cardiovascular-diseases-(cvds)."},{"key":"ref_3","unstructured":"Laughlin, C.D., and D\u2019Aquili, E.G. (1974). Biogenetic Structuralism, Columbia University Press."},{"key":"ref_4","first-page":"420","article-title":"Biogenetic Structuralism","volume":"49","author":"Leavy","year":"1976","journal-title":"Yale J. Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"i2","DOI":"10.1136\/hrt.2005.077875","article-title":"Anatomy, echocardiography, and normal right ventricular dimensions","volume":"92","author":"Ho","year":"2006","journal-title":"Heart"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Jalilinejad, N., Rabiee, M., Baheiraei, N., Ghahremanzadeh, R., Salarian, R., Rabiee, N., Akhavan, O., Zarrintaj, P., Hejna, A., and Saeb, M.R. (2022). Electrically conductive carbon-based (bio)-nanomaterials for cardiac tissue engineering. Bioeng. Transl. Med., 8.","DOI":"10.1002\/btm2.10347"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0008-6363(98)00044-3","article-title":"Cardiac endothelium and myocardial function","volume":"38","author":"Brutsaert","year":"1998","journal-title":"Cardiovasc. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1124\/dmd.119.086611","article-title":"Overview of the components of cardiac metabolism","volume":"47","author":"Hausner","year":"2019","journal-title":"Drug Metab. Disposit."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1046\/j.1469-7580.2002.00059.x","article-title":"Endothelial barriers: From hypothetical pores to membrane proteins","volume":"200","author":"Firth","year":"2002","journal-title":"J. Anat."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Nevola, R., Villani, A., Imbriani, S., Alfano, M., Criscuolo, L., Beccia, D., Ruocco, R., Femine, A.D., Gragnano, F., and Cozzolino, D. (2023). Sodium-Glucose Co-Transporters Family: Current Evidence, Clinical Applications and Perspectives. Front. Biosci. (Landmark Ed), 28.","DOI":"10.31083\/j.fbl2805103"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0300-9629(96)00399-4","article-title":"Binding of 125I-Insulin on Capillary Endothelial and Myofiber Cell Membranes in Normal and Streptozotocin-Induced Diabetic Perfused Rat Hearts","volume":"117","author":"Haddad","year":"1997","journal-title":"Comp. Biochem. Physiol. Part A Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Xuan, Y., Chen, C., Wen, Z., and Wang, D.W. (2022). The Roles of Cardiac Fibroblasts and Endothelial Cells in Myocarditis. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.882027"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hennigs, J.K., Matuszcak, C., Trepel, M., and K\u00f6rbelin, J. (2021). Vascular Endothelial Cells: Heterogeneity and Targeting Approaches. Cells, 10.","DOI":"10.3390\/cells10102712"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.1073\/pnas.0304987101","article-title":"Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney","volume":"101","author":"Mikkaichi","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"777","DOI":"10.2165\/00003088-200746090-00005","article-title":"Increased absorption of digoxin from the human jejunum due to inhibition of intestinal transporter-mediated efflux","volume":"46","author":"Igel","year":"2007","journal-title":"Clin. Pharmacokinet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ijpharm.2006.05.030","article-title":"The complexity of intestinal absorption and exsorption of digoxin in rats","volume":"322","author":"Yao","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1111\/j.1349-7006.2007.00538.x","article-title":"Mechanism of multidrug recognition by MDR1\/ABCB1","volume":"98","author":"Kimura","year":"2007","journal-title":"Cancer Sci."},{"key":"ref_18","first-page":"S12","article-title":"The modern-day role of digoxin in heart failure and atrial fibrillation\u2014Benefits and limitations","volume":"31","author":"Thompson","year":"2024","journal-title":"Br. J. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"194","DOI":"10.12729\/jbr.2014.15.4.194","article-title":"Na,K-ATPase \u03b22 isoform (atp1b2) expressed in the retina of Xenopus","volume":"15","author":"Rahman","year":"2014","journal-title":"J. Biomed. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Afzal, O., Altamimi, A.S.A., Nadeem, M.S., Alzarea, S.I., Almalki, W.H., Tariq, A., Mubeen, B., Murtaza, B.N., Iftikhar, S., and Riaz, N. (2022). Nanoparticles in Drug Delivery: From History to Therapeutic Applications. Nanomaterials, 12.","DOI":"10.3390\/nano12244494"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1021\/acscentsci.6b00190","article-title":"Does nanomedicine have a delivery problem?","volume":"2","author":"Torrice","year":"2016","journal-title":"ACS Cent. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"81","DOI":"10.7150\/thno.7193","article-title":"Improving Conventional Enhanced Permeability and Retention (EPR) Effects; What Is the Appropriate Target?","volume":"4","author":"Kobayashi","year":"2014","journal-title":"Theranostics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8702","DOI":"10.1007\/s12035-024-04015-9","article-title":"Receptor-Assisted Nanotherapeutics for Overcoming the Blood\u2013Brain Barrier","volume":"61","author":"Mhaske","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41573-021-00139-y","article-title":"Strategies for delivering therapeutics across the blood\u2013brain barrier","volume":"20","author":"Terstappen","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Abdullah, C.S., Alam, S., Aishwarya, R., Miriyala, S., Bhuiyan, M.A.N., Panchatcharam, M., Pattillo, C.B., Orr, A.W., Sadoshima, J., and Hill, J.A. (2019). Doxorubicin-induced cardiomyopathy associated with inhibition of autophagic degradation process and defects in mitochondrial respiration. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-37862-3"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1002\/cncr.11407","article-title":"Congestive heart failure in patients treated with doxorubicin","volume":"97","author":"Swain","year":"2003","journal-title":"Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"710","DOI":"10.7326\/0003-4819-91-5-710","article-title":"Risk Factors for Doxorubicin-induced Congestive Heart Failure","volume":"91","author":"Layard","year":"1979","journal-title":"Ann. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.ejcts.2006.06.024","article-title":"Doxorubicin in experimental and clinical heart failure","volume":"30","author":"Christiansen","year":"2006","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Teran-Saavedra, N.G., Sarabia-Sainz, J.A., Vel\u00e1zquez-Contreras, E.F., Ramos-Clamont Montfort, G., Pedroza-Montero, M., and Vazquez-Moreno, L. (2020). Albumin-Albumin\/Lactosylated Core-Shell Nanoparticles: Therapy to Treat Hepatocellular Carcinoma for Controlled Delivery of Doxorubicin. Molecules, 25.","DOI":"10.3390\/molecules25225432"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.jconrel.2012.02.011","article-title":"Drug targeting to the diseased liver","volume":"161","author":"Poelstra","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_31","first-page":"e21154","article-title":"Potential Therapeutic Treatments for Doxorubicin-Induced Cardiomyopathy","volume":"14","author":"Kabir","year":"2022","journal-title":"Cureus"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1161\/CIRCRESAHA.111.300003","article-title":"Phosphodiesterase type 3A regulates basal myocardial contractility through interacting with sarcoplasmic reticulum calcium ATPase type 2a signaling complexes in mouse heart","volume":"112","author":"Beca","year":"2013","journal-title":"Circ. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1073\/pnas.97.2.931","article-title":"Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling","volume":"97","author":"Paradis","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"H1900","DOI":"10.1152\/ajpheart.00379.2007","article-title":"Role of cardiac overexpression of angiotensin II in the regulation of cardiac function and remodeling post-myocardial infarction","volume":"293","author":"Xu","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lomis, N., Sarfaraz, Z.K., Alruwaih, A., Westfall, S., Shum-Tim, D., and Prakash, S. (2021). Albumin Nanoparticle Formulation for Heart-Targeted Drug Delivery: In Vivo Assessment of Congestive Heart Failure. Pharmaceuticals, 14.","DOI":"10.3390\/ph14070697"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1083\/jcb.201008117","article-title":"Local clustering of transferrin receptors promotes clathrin-coated pit initiation","volume":"191","author":"Liu","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5330","DOI":"10.1128\/JVI.07194-11","article-title":"Limited transferrin receptor clustering allows rapid diffusion of canine parvovirus into clathrin endocytic structures","volume":"86","author":"Cureton","year":"2012","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1083\/jcb.142.1.59","article-title":"The LDL Receptor Clustering Motif Interacts with the Clathrin Terminal Domain in a Reverse Turn Conformation","volume":"142","author":"Kibbey","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"123","DOI":"10.4236\/abb.2020.114010","article-title":"Antagonism of Angiotensin II AT1 Receptor and Silencing of CD44 Gene Expression Inhibit Cardiac Fibroblast Activation via Modulating TGF-\u03b21\/Smad Signaling Pathway","volume":"11","author":"Bai","year":"2020","journal-title":"Adv. Biosci. Biotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"H246","DOI":"10.1152\/ajpheart.1992.262.1.H246","article-title":"gp60 is an albumin-binding glycoprotein expressed by continuous endothelium involved in albumin transcytosis","volume":"262","author":"Schnitzer","year":"1992","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1248\/yakushi.15-00227-1","article-title":"Human Serum Albumin as Carrier in Drug Delivery Systems","volume":"136","author":"Ishima","year":"2016","journal-title":"Yakugaku Zasshi"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/hr.2012.55","article-title":"Does angiotensin II cross the blood\u2013brain barrier?","volume":"35","author":"Roncevic","year":"2012","journal-title":"Hypertens. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature03817","article-title":"Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis","volume":"436","author":"Zhao","year":"2005","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.nano.2017.12.004","article-title":"Delivery of microRNA-1 inhibitor by dendrimer-based nanovector: An early targeting therapy for myocardial infarction in mice","volume":"14","author":"Xue","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1177\/1358836X9800300206","article-title":"Myocardial angiotensin II receptor expression and ischemia-reperfusion injury","volume":"3","author":"Yang","year":"1998","journal-title":"Vasc. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1177\/2047487319870344","article-title":"Oxidative stress and inflammation in the evolution of heart failure: From pathophysiology to therapeutic strategies","volume":"27","author":"Aimo","year":"2020","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tabish, T.A., Hayat, H., Abbas, A., and Narayan, R.J. (2022). Graphene Quantum Dots-Based Electrochemical Biosensing Platform for Early Detection of Acute Myocardial Infarction. Biosensors, 12.","DOI":"10.3390\/bios12020077"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1097\/FJC.0000000000001410","article-title":"Treatment for Myocardial Infarction: In Vivo Evaluation of Curcumin-Loaded PEGylated-GQD Nanoparticles","volume":"81","author":"Rostamzadeh","year":"2023","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"105790","DOI":"10.1016\/j.neuint.2024.105790","article-title":"Curcumin as a potential therapeutic agent for treating neurodegenerative diseases","volume":"178","author":"Purushotham","year":"2024","journal-title":"Neurochem. Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"111658","DOI":"10.1016\/j.ejmech.2019.111658","article-title":"Mechanics insights of curcumin in myocardial ischemia: Where are we standing?","volume":"183","author":"Ahmed","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhao, J., Chen, Y., Chen, Q., Hong, T., Zhong, Z., He, J., and Ni, C. (2022). Curcumin Ameliorates Cardiac Fibrosis by Regulating Macrophage-Fibroblast Crosstalk via IL18-P-SMAD2\/3 Signaling Pathway Inhibition. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.784041"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Mishra, P., Sahoo, D.K., Mohanty, C., and Samanta, L. (2024). Curcumin-loaded nanoparticles effectively prevent T4-induced oxidative stress in rat heart. Cell Biochem. Funct., 42.","DOI":"10.1002\/cbf.4070"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1136\/ard.2005.048637","article-title":"Methotrexate modulates the kinetics of adenosine in humans in vivo","volume":"65","author":"Riksen","year":"2006","journal-title":"Ann. Rheum. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"H1262","DOI":"10.1152\/ajpheart.00181.2010","article-title":"Both A2a and A2b adenosine receptors at reperfusion are necessary to reduce infarct size in mouse hearts","volume":"299","author":"Methner","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.2147\/IJN.S129324","article-title":"Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats","volume":"12","author":"Guido","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6163","DOI":"10.7150\/thno.28021","article-title":"Hypoxia-elicited mesenchymal stem cell-derived exosomes facilitates cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction","volume":"8","author":"Zhu","year":"2018","journal-title":"Theranostics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1158\/1541-7786.MCR-18-0891","article-title":"Internalization of Exosomes through Receptor-Mediated Endocytosis","volume":"17","author":"Gonda","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.2217\/nnm-2020-0206","article-title":"Measurement and Standardization Challenges for Exosome-Based Delivery Vectors","volume":"15","author":"Nelson","year":"2020","journal-title":"Nanomedicine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5803","DOI":"10.1039\/D4NA00501E","article-title":"A comprehensive review of challenges and advances in exosome-based drug delivery systems","volume":"6","author":"Palakurthi","year":"2024","journal-title":"Nanoscale Adv."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"18667","DOI":"10.1021\/acsnano.2c07311","article-title":"Light-Activated Gold\u2013Selenium Core\u2013Shell Nanocomposites with NIR-II Photoacoustic Imaging Performances for Heart-Targeted Repair","volume":"16","author":"Sun","year":"2022","journal-title":"ACS Nano"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/jat.4499","article-title":"Toxicological effects of selenium nanoparticles in laboratory animals: A review","volume":"44","author":"Ryabova","year":"2024","journal-title":"J. Appl. Toxicol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.yjmcc.2011.02.003","article-title":"Identification of Targeting Peptides for Ischemic Myocardium by In Vivo Phage Display","volume":"50","author":"Kanki","year":"2011","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.biomaterials.2016.03.046","article-title":"In vitro and in vivo assessment of heart-homing porous silicon nanoparticles","volume":"94","author":"Ferreira","year":"2016","journal-title":"Biomaterials"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"124569","DOI":"10.1016\/j.ijpharm.2024.124569","article-title":"Myocardium-targeted liposomal delivery of the antioxidant peptide 8P against doxorubicin-induced myocardial injury","volume":"663","author":"Zhao","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4671","DOI":"10.1007\/s11010-025-05289-w","article-title":"Endothelial dysfunction in cardiovascular diseases: Mechanisms and in vitro models","volume":"480","author":"Grego","year":"2025","journal-title":"Mol. Cell. Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1002\/jcp.25575","article-title":"Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy","volume":"232","author":"Yun","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"C589","DOI":"10.1152\/ajpcell.00235.2017","article-title":"Interleukin-6 promotes a sustained loss of endothelial barrier function via Janus kinase-mediated STAT3 phosphorylation and de novo protein synthesis","volume":"314","author":"Alsaffar","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Clark, P.R., Kim, R.K., Pober, J.S., and Kluger, M.S. (2015). Tumor Necrosis Factor Disrupts Claudin-5 Endothelial Tight Junction Barriers in Two Distinct NF-\u03baB-Dependent Phases. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120075"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2308446","DOI":"10.1002\/adfm.202308446","article-title":"Exploring and Analyzing the Systemic Delivery Barriers for Nanoparticles","volume":"34","author":"Wang","year":"2023","journal-title":"Adv. Funct. Mater."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1210\/er.2007-0006","article-title":"Cardiovascular actions of insulin","volume":"28","author":"Muniyappa","year":"2007","journal-title":"Endocr. Rev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1248\/cpb.c19-00854","article-title":"Smart Strategies for Therapeutic Agent Delivery into Brain across the Blood\u2013Brain Barrier Using Receptor-Mediated Transcytosis","volume":"68","author":"Tashima","year":"2020","journal-title":"Chem. Pharm. Bull."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1183\/09031936.03.00075302","article-title":"Variable tissue expression of transferrin receptors: Relevance to acute respiratory distress syndrome","volume":"22","author":"Upton","year":"2003","journal-title":"Eur. Respir. J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2016.06.036","article-title":"Development of antibody-siRNA conjugate targeted to cardiac and skeletal muscles","volume":"237","author":"Sugo","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"010601","DOI":"10.1063\/5.0191034","article-title":"A review of magnetic nanoparticles used in nanomedicine","volume":"12","author":"Selim","year":"2024","journal-title":"APL Mater."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/s41551-020-00637-1","article-title":"Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles","volume":"4","author":"Liu","year":"2020","journal-title":"Nat. Biomed. Eng."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jmmm.2018.09.118","article-title":"The use of magnetic targeting for drug delivery into cardiac myocytes","volume":"473","author":"Lim","year":"2019","journal-title":"J. Magn. Magn. Mater."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.jaci.2020.07.015","article-title":"Neonatal Fc receptor in human immunity: Function and role in therapeutic intervention","volume":"146","author":"Patel","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"8569225","DOI":"10.1155\/2021\/8569225","article-title":"PEGylated Graphene Quantum Dot Improved Cardiac Function in Rats with Myocardial Infarction: Morphological, Oxidative Stress, and Toxicological Evidences","volume":"2021","author":"Rostamzadeh","year":"2021","journal-title":"Oxid. Med. Cell. Longev."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/11\/1365\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:28:52Z","timestamp":1761182932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/11\/1365"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,22]]},"references-count":78,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["pharmaceutics17111365"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17111365","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,22]]}}}