{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:43:32Z","timestamp":1793317412494,"version":"4.5.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006034","name":"University of Southern California","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006034","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013829","name":"Alfred E. Mann Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013829","id-type":"DOI","asserted-by":"publisher"}]},{"name":"New Innovator Award","award":["DP2-DK121328"],"award-info":[{"award-number":["DP2-DK121328"]}]},{"name":"NSF EAGER","award":["2132744"],"award-info":[{"award-number":["2132744"]}]},{"name":"WISE Major Support Award"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD021833"],"award-info":[{"award-number":["S10OD021833"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chronic and genetic kidney diseases such as autosomal dominant polycystic kidney disease (ADPKD) have few therapeutic options, and clinical trials testing small molecule drugs have been unfavorable due to low kidney bioavailability and adverse side effects. Although nanoparticles can be designed to deliver drugs directly to the diseased site, there are no kidney-targeted nanomedicines clinically available, and most FDA-approved nanoparticles are administered intravenously which is not ideal for chronic diseases. To meet these challenges of chronic diseases, we developed a biomaterials-based strategy using chitosan particles (CP) for oral delivery of therapeutic, kidney-targeting peptide amphiphile micelles (KMs). We hypothesized that encapsuling KMs into CP would enhance the bioavailability of KMs upon oral administration given the high stability of chitosan in acidic conditions and mucoadhesive properties enabling absorption within the intestines. To test this, we evaluated the mechanism of KM access to the kidneys via intravital imaging and investigated the KM biodistribution in a porcine model. Next, we loaded KMs carrying the ADPKD drug metformin into CP (KM-CP-met) and measured in vitro therapeutic effect. Upon oral administration in vivo, KM-CP-met showed significantly greater bioavailability and accumulation in the kidneys as compared to KM only or free drug. As such, KM-CP-met treatment in ADPKD mice (Pkd1fl\/fl;Pax8-rtTA;Tet-O-Cre which develops the disease over 120 days and mimics the slow development of ADPKD) showed enhanced therapeutic efficacy without affecting safety despite repeated treatment. Herein, we demonstrate the potential of KM-CP as a nanomedicine strategy for oral delivery for the long-term treatment of chronic kidney diseases.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgae187","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T11:27:15Z","timestamp":1715340435000},"source":"Crossref","is-referenced-by-count":12,"title":["Oral delivery of nanomedicine for genetic kidney disease"],"prefix":"10.1093","volume":"3","author":[{"given":"Yi","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Southern California , Los Angeles, CA 90089 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3184-2705","authenticated-orcid":false,"given":"Jonathan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Southern California , Los Angeles, CA 90089 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Mancino","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033 , USA"},{"name":"USC\/UKRO Kidney Research Center, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033 , USA"},{"name":"USC\/UKRO Kidney Research Center, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette","family":"O\u2019Grady","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Southern California , Los Angeles, CA 90089 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033 , USA"},{"name":"USC\/UKRO Kidney Research Center, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0166-0209","authenticated-orcid":false,"given":"Kairui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Southern California , Los Angeles, CA 90089 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Chin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Southern California , Los Angeles, CA 90089 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9797-7162","authenticated-orcid":false,"given":"Christopher","family":"Poon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Southern California , Los Angeles, CA 90089 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Yin","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033 , USA"},{"name":"USC\/UKRO Kidney Research Center, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina","family":"Gyarmati","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience, and Medicine, Zilkha Neurogenetic Institute, University of Southern California , Los Angeles, CA 90033 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Peti-Peterdi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience, and Medicine, Zilkha Neurogenetic Institute, University of Southern California , Los Angeles, CA 90033 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth R","family":"Hallows","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033 , USA"},{"name":"USC\/UKRO Kidney Research Center, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7726-5555","authenticated-orcid":false,"given":"Eun Ji","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Southern California , Los Angeles, CA 90089 , USA"},{"name":"Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033 , USA"},{"name":"Department of Chemical Engineering and Materials Science, University of Southern California , Los Angeles, CA 90089 , USA"},{"name":"Department of Surgery, Division of Vascular Surgery and Endovascular Therapy, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033 , USA"},{"name":"Department of Stem Cell Biology and Regenerative Medicine, University of Southern California , Los Angeles, CA 90089 , USA"},{"name":"Norris Comprehensive Cancer Center, University of Southern California , Los Angeles, CA 90033 , USA"},{"name":"Bridge Institute, University of Southern California , Los Angeles, CA 90089 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"issue":"3","key":"2024053108512334300_pgae187-B1","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1046\/j.1523-1755.2000.00250.x","article-title":"Estimating prevalence in single-gene kidney diseases progressing to renal failure","volume":"58","author":"Levy","year":"2000","journal-title":"Kidney Int"},{"issue":"9","key":"2024053108512334300_pgae187-B2","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1097\/01.ASN.0000028643.17901.42","article-title":"Genetics and pathogenesis of polycystic kidney disease","volume":"13","author":"Igarashi","year":"2002","journal-title":"J Am Soc Nephrol"},{"issue":"2","key":"2024053108512334300_pgae187-B3","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/s41401-022-00937-z","article-title":"1-Indanone retards cyst development in ADPKD mouse model by stabilizing tubulin and down-regulating anterograde transport of cilia","volume":"44","author":"Li","year":"2022","journal-title":"Acta Pharmacol Sin"},{"issue":"1","key":"2024053108512334300_pgae187-B4","doi-asserted-by":"crossref","first-page":"4320","DOI":"10.1038\/s41467-020-18104-5","article-title":"Cyst growth in ADPKD is prevented by pharmacological and genetic inhibition of TMEM16A in vivo","volume":"11","author":"Cabrita","year":"2020","journal-title":"Nat Commun"},{"key":"2024053108512334300_pgae187-B5","doi-asserted-by":"crossref","first-page":"109648","DOI":"10.1016\/j.cellsig.2020.109648","article-title":"Molecular pathways involved in injury-repair and ADPKD progression","volume":"72","author":"Formica","year":"2020","journal-title":"Cell Signal"},{"issue":"6","key":"2024053108512334300_pgae187-B6","first-page":"e4842","article-title":"Tolvaptan-induced liver injury: who is at risk? A case report and literature review","volume":"11","author":"Khan","year":"2019","journal-title":"Cureus"},{"issue":"25","key":"2024053108512334300_pgae187-B7","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1056\/NEJMoa1205511","article-title":"Tolvaptan in patients with autosomal dominant polycystic kidney disease","volume":"367","author":"Torres","year":"2012","journal-title":"N Engl J Med"},{"issue":"3","key":"2024053108512334300_pgae187-B8","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.jhep.2011.08.020","article-title":"Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis","volume":"56","author":"Cardenas","year":"2012","journal-title":"J Hepatol"},{"issue":"3","key":"2024053108512334300_pgae187-B9","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1053\/j.ajkd.2018.09.016","article-title":"Determinants of urine volume in ADPKD patients using the vasopressin V2 receptor antagonist tolvaptan","volume":"73","author":"Kramers","year":"2019","journal-title":"Am J Kidney Dis"},{"issue":"3","key":"2024053108512334300_pgae187-B10","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s40265-019-1056-1","article-title":"Tolvaptan: a review in autosomal dominant polycystic kidney disease","volume":"79","author":"Blair","year":"2019","journal-title":"Drugs"},{"issue":"1","key":"2024053108512334300_pgae187-B11","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1186\/s12882-019-1612-7","article-title":"Idiosyncratic hepatic toxicity in autosomal dominant polycystic kidney disease (ADPKD) patient in combined treatment with tolvaptan and amoxicillin\/clavulanic acid: a case report","volume":"20","author":"Pellegrino","year":"2019","journal-title":"BMC Nephrol"},{"issue":"2","key":"2024053108512334300_pgae187-B12","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s40620-019-00679-y","article-title":"ADPKD current management and ongoing trials","volume":"33","author":"Testa","year":"2020","journal-title":"J Nephrol"},{"issue":"Supp_1","key":"2024053108512334300_pgae187-B13","doi-asserted-by":"crossref","first-page":"gfz096-FO006","DOI":"10.1093\/ndt\/gfz096.FO006","article-title":"The Nrf2 activator bardoxolone methyl inhibits cyst formation, reduces inflammation, and improves mitochondrial function in cellular models of polycystic kidney disease","volume":"34","author":"Miller","year":"2019","journal-title":"Nephrol Dial Transplant"},{"issue":"10","key":"2024053108512334300_pgae187-B14","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s10157-020-01917-5","article-title":"Bardoxolone methyl: drug development for diabetic kidney disease","volume":"24","author":"Kanda","year":"2020","journal-title":"Clin Exp Nephrol"},{"issue":"1","key":"2024053108512334300_pgae187-B15","doi-asserted-by":"crossref","first-page":"F27","DOI":"10.1152\/ajprenal.00298.2021","article-title":"Metformin improves relevant disease parameters in an autosomal dominant polycystic kidney disease mouse model","volume":"322","author":"Pastor-Soler","year":"2022","journal-title":"Am J Physiol Renal Physiol"},{"issue":"3","key":"2024053108512334300_pgae187-B16","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.kint.2021.06.013","article-title":"Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD)","volume":"100","author":"Perrone","year":"2021","journal-title":"Kidney Int"},{"issue":"2","key":"2024053108512334300_pgae187-B17","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2165\/11534750-000000000-00000","article-title":"Clinical pharmacokinetics of metformin","volume":"50","author":"Graham","year":"2011","journal-title":"Clin Pharmacokinet"},{"issue":"6","key":"2024053108512334300_pgae187-B18","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1073\/pnas.1011498108","article-title":"Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis","volume":"108","author":"Takiar","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"issue":"10","key":"2024053108512334300_pgae187-B19","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1093\/hmg\/ddab340","article-title":"Metformin induces lactate accumulation and accelerates renal cyst progression in Pkd1-deficient mice","volume":"31","author":"Chang","year":"2021","journal-title":"Hum Mol Genet"},{"issue":"5","key":"2024053108512334300_pgae187-B20","first-page":"1","article-title":"Fibrin-targeting, peptide amphiphile micelles as contrast agents for molecular MRI","volume":"5","author":"Chung","year":"2014","journal-title":"J Cell Sci Ther"},{"issue":"3","key":"2024053108512334300_pgae187-B21","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1002\/adhm.201400336","article-title":"Monocyte-targeting supramolecular micellar assemblies: a molecular diagnostic tool for atherosclerosis","volume":"4","author":"Chung","year":"2015","journal-title":"Adv Healthc Mater"},{"issue":"3","key":"2024053108512334300_pgae187-B22","doi-asserted-by":"crossref","first-page":"e10173","DOI":"10.1002\/btm2.10173","article-title":"The effect of size, charge, and peptide ligand length on kidney targeting by small, organic nanoparticles","volume":"5","author":"Huang","year":"2020","journal-title":"Bioeng Transl Med"},{"key":"2024053108512334300_pgae187-B23","doi-asserted-by":"crossref","first-page":"120810","DOI":"10.1016\/j.biomaterials.2021.120810","article-title":"miR-145 micelles mitigate atherosclerosis by modulating vascular smooth muscle cell phenotype","volume":"273","author":"Chin","year":"2021","journal-title":"Biomaterials"},{"key":"2024053108512334300_pgae187-B24","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.jconrel.2020.09.054","article-title":"CCR2-targeted micelles for anti-cancer peptide delivery and immune stimulation","volume":"329","author":"Trac","year":"2021","journal-title":"J Control Release"},{"issue":"10","key":"2024053108512334300_pgae187-B25","doi-asserted-by":"crossref","first-page":"5584","DOI":"10.1007\/s12274-018-2100-2","article-title":"Design and in vivo characterization of kidney-targeting multimodal micelles for renal drug delivery","volume":"11","author":"Wang","year":"2018","journal-title":"Nano Res"},{"issue":"1","key":"2024053108512334300_pgae187-B26","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s12195-022-00753-9","article-title":"Combining metformin and drug-loaded kidney-targeting micelles for polycystic kidney disease","volume":"16","author":"Jiang","year":"2023","journal-title":"Cell Mol Bioeng"},{"issue":"4","key":"2024053108512334300_pgae187-B27","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.slast.2023.02.001","article-title":"In vitro delivery of mTOR inhibitors by kidney-targeted micelles for autosomal dominant polycystic kidney disease","volume":"28","author":"Cox","year":"2023","journal-title":"SLAS Technol"},{"key":"2024053108512334300_pgae187-B28","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jconrel.2021.04.016","article-title":"Improving kidney targeting: the influence of nanoparticle physicochemical properties on kidney interactions","volume":"334","author":"Huang","year":"2021","journal-title":"J Control Release"},{"issue":"7","key":"2024053108512334300_pgae187-B29","doi-asserted-by":"crossref","first-page":"6165","DOI":"10.1021\/acsnano.2c12140","article-title":"Spotlight on genetic kidney diseases: a call for drug delivery and nanomedicine solutions","volume":"17","author":"Trac","year":"2023","journal-title":"ACS Nano"},{"issue":"5","key":"2024053108512334300_pgae187-B30","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s12195-020-00622-3","article-title":"Transdermal delivery of kidney-targeting nanoparticles using dissolvable microneedles","volume":"13","author":"Tripathy","year":"2020","journal-title":"Cell Mol Bioeng"},{"issue":"2","key":"2024053108512334300_pgae187-B31","doi-asserted-by":"crossref","first-page":"026111","DOI":"10.1063\/5.0151408","article-title":"Targeting the ADPKD methylome using nanoparticle-mediated combination therapy","volume":"7","author":"Trinh","year":"2023","journal-title":"APL Bioeng"},{"issue":"3","key":"2024053108512334300_pgae187-B32","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1021\/acsnano.3c09201","article-title":"MRI detection of lymph node metastasis through molecular targeting of C-C chemokine receptor type 2 and monocyte hitchhiking","volume":"18","author":"Trac","year":"2024","journal-title":"ACS Nano"},{"key":"2024053108512334300_pgae187-B33","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1021\/acs.biomac.3c01397","article-title":"Investigation of basolateral targeting micelles for drug delivery applications in polycystic kidney disease","volume":"25","author":"Huang","year":"2024","journal-title":"Biomacromolecules"},{"key":"2024053108512334300_pgae187-B34","first-page":"765","article-title":"Recent advances of chitosan nanoparticles as drug carriers","volume":"6","author":"Wang","year":"2011","journal-title":"Int J Nanomed"},{"key":"2024053108512334300_pgae187-B35","doi-asserted-by":"crossref","first-page":"e2833","DOI":"10.1590\/1518-8345.1457.2833","article-title":"Risk factors for complications in peripheral intravenous catheters in adults: secondary analysis of a randomized controlled trial","volume":"24","author":"Johann","year":"2016","journal-title":"Rev Lat Am Enfermagem"},{"key":"2024053108512334300_pgae187-B36","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.jconrel.2020.10.047","article-title":"Oral delivery of metformin by chitosan nanoparticles for polycystic kidney disease","volume":"329","author":"Wang","year":"2021","journal-title":"J Control Release"},{"issue":"1","key":"2024053108512334300_pgae187-B37","doi-asserted-by":"crossref","first-page":"e10342","DOI":"10.1002\/btm2.10342","article-title":"Long-term daily oral administration of intestinal permeation enhancers is safe and effective in mice","volume":"8","author":"Fein","year":"2023","journal-title":"Bioeng Transl Med"},{"key":"2024053108512334300_pgae187-B38","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.carbpol.2014.12.084","article-title":"Solid lipid nanoparticles for oral drug delivery: chitosan coating improves stability, controlled delivery, mucoadhesion and cellular uptake","volume":"122","author":"Luo","year":"2015","journal-title":"Carbohydr Polym"},{"issue":"1","key":"2024053108512334300_pgae187-B39","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.carbpol.2013.06.064","article-title":"Development of chitosan-based nanoparticles through inter-polymeric complexation for oral drug delivery","volume":"98","author":"Jana","year":"2013","journal-title":"Carbohydr Polym"},{"issue":"1","key":"2024053108512334300_pgae187-B40","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1021\/mp100289v","article-title":"Stearic acid-g-chitosan polymeric micelle for oral drug delivery: in vitro transport and in vivo absorption","volume":"8","author":"Yuan","year":"2011","journal-title":"Mol Pharm"},{"issue":"37","key":"2024053108512334300_pgae187-B41","doi-asserted-by":"crossref","first-page":"5944","DOI":"10.1002\/anie.200501428","article-title":"Intracellular protein degradation: from a vague idea, through the lysosome and the ubiquitin-proteasome system, and onto human diseases and drug targeting (Nobel lecture)","volume":"44","author":"Ciechanover","year":"2005","journal-title":"Angew Chem Int Ed Engl"},{"issue":"46","key":"2024053108512334300_pgae187-B42","doi-asserted-by":"crossref","first-page":"19310","DOI":"10.1073\/pnas.0908958106","article-title":"Global profiling of protease cleavage sites by chemoselective labeling of protein N-termini","volume":"106","author":"Xu","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"2024053108512334300_pgae187-B43","doi-asserted-by":"crossref","first-page":"851","DOI":"10.3892\/ijmm.2017.2902","article-title":"Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes","volume":"39","author":"Wu","year":"2017","journal-title":"Int J Mol Med"},{"issue":"1","key":"2024053108512334300_pgae187-B44","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1038\/s41598-018-19628-z","article-title":"Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings","volume":"8","author":"Feng","year":"2018","journal-title":"Sci Rep"},{"issue":"1","key":"2024053108512334300_pgae187-B45","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1021\/acsnano.5b05066","article-title":"Short- and long-term tracking of anionic ultrasmall nanoparticles in kidney","volume":"10","author":"Liang","year":"2016","journal-title":"ACS Nano"},{"issue":"14","key":"2024053108512334300_pgae187-B46","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1002\/anie.201007321","article-title":"Luminescent gold nanoparticles with efficient renal clearance","volume":"50","author":"Zhou","year":"2011","journal-title":"Angew Chem Int Ed Engl"},{"issue":"16","key":"2024053108512334300_pgae187-B47","doi-asserted-by":"crossref","first-page":"6656","DOI":"10.1073\/pnas.1103573108","article-title":"Targeting kidney mesangium by nanoparticles of defined size","volume":"108","author":"Choi","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"issue":"Pt 1","key":"2024053108512334300_pgae187-B48","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.ijbiomac.2017.07.161","article-title":"Chitosan coated PluronicF127 micelles for effective delivery of Amphotericin B in experimental visceral leishmaniasis","volume":"105","author":"Singh","year":"2017","journal-title":"Int J Biol Macromol"},{"issue":"11","key":"2024053108512334300_pgae187-B49","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1248\/cpb.58.1423","article-title":"Chitosan nanoparticles: a promising system in novel drug delivery","volume":"58","author":"Nagpal","year":"2010","journal-title":"Chem Pharm Bull (Tokyo)"},{"key":"2024053108512334300_pgae187-B50","doi-asserted-by":"crossref","first-page":"903","DOI":"10.2147\/IJN.S148305","article-title":"EGFR-targeted photodynamic therapy by curcumin-encapsulated chitosan\/TPP nanoparticles","volume":"13","author":"Tsai","year":"2018","journal-title":"Int J Nanomedicine"},{"issue":"5","key":"2024053108512334300_pgae187-B51","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1021\/mp200572t","article-title":"Opening of epithelial tight junctions and enhancement of paracellular permeation by chitosan: microscopic, ultrastructural, and computed-tomographic observations","volume":"9","author":"Sonaje","year":"2012","journal-title":"Mol Pharm"},{"issue":"1","key":"2024053108512334300_pgae187-B52","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/s41551-019-0465-5","article-title":"Anionic nanoparticles enable the oral delivery of proteins by enhancing intestinal permeability","volume":"4","author":"Lamson","year":"2020","journal-title":"Nat Biomed Eng"},{"key":"2024053108512334300_pgae187-B53","doi-asserted-by":"crossref","first-page":"992","DOI":"10.3389\/fbioe.2020.00992","article-title":"Bioengineering novel in vitro co-culture models that represent the human intestinal mucosa with improved Caco-2 structure and barrier function","volume":"8","author":"Darling","year":"2020","journal-title":"Front Bioeng Biotechnol"},{"issue":"3","key":"2024053108512334300_pgae187-B54","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0955-2863(01)00208-X","article-title":"The effect of chitosan and other polycations on tight junction permeability in the human intestinal Caco-2 cell line","volume":"13","author":"Ranaldi","year":"2002","journal-title":"J Nutrit Biochem"},{"issue":"2","key":"2024053108512334300_pgae187-B55","doi-asserted-by":"crossref","first-page":"195","DOI":"10.15171\/apb.2019.023","article-title":"Current advances in chitosan nanoparticles based drug delivery and targeting","volume":"9","author":"Garg","year":"2019","journal-title":"Adv Pharm Bull"},{"issue":"42","key":"2024053108512334300_pgae187-B56","doi-asserted-by":"crossref","first-page":"43940","DOI":"10.1074\/jbc.M404421200","article-title":"Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo: role of mitochondrial reactive nitrogen species","volume":"279","author":"Zou","year":"2004","journal-title":"J Biol Chem"},{"issue":"9","key":"2024053108512334300_pgae187-B57","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1038\/ng.2715","article-title":"Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease","volume":"45","author":"Ma","year":"2013","journal-title":"Nat Genet"},{"issue":"18","key":"2024053108512334300_pgae187-B58","doi-asserted-by":"crossref","first-page":"e14197","DOI":"10.14814\/phy2.14197","article-title":"Establishing equivalent diabetes in male and female Nos3-deficient mice results in a comparable onset of diabetic kidney injury","volume":"7","author":"Tian","year":"2019","journal-title":"Physiol Rep"},{"issue":"14","key":"2024053108512334300_pgae187-B59","doi-asserted-by":"crossref","first-page":"11001","DOI":"10.1007\/s11356-015-4324-y","article-title":"The impact of aluminum, fluoride, and aluminum-fluoride complexes in drinking water on chronic kidney disease","volume":"22","author":"Wasana","year":"2015","journal-title":"Environ Sci Pollut Res Int"},{"issue":"12","key":"2024053108512334300_pgae187-B60","first-page":"742","article-title":"Progress in nanomedicine: approved and investigational nanodrugs","volume":"42","author":"Ventola","year":"2017","journal-title":"P T"},{"issue":"4","key":"2024053108512334300_pgae187-B61","doi-asserted-by":"crossref","first-page":"523","DOI":"10.2217\/nnm.10.23","article-title":"Understanding and overcoming major barriers in cancer nanomedicine","volume":"5","author":"Nie","year":"2010","journal-title":"Nanomedicine (Lond)"},{"issue":"Suppl 1","key":"2024053108512334300_pgae187-B62","doi-asserted-by":"crossref","first-page":"S83","DOI":"10.1007\/s10557-011-6357-x","article-title":"Nonclinical pharmacokinetics of a new nonpeptide V2 receptor antagonist, tolvaptan","volume":"25","author":"Furukawa","year":"2011","journal-title":"Cardiovasc Drugs Ther"},{"issue":"5","key":"2024053108512334300_pgae187-B63","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1681\/ASN.V105923","article-title":"Corticosteroid-dependent sodium transport in a novel immortalized mouse collecting duct principal cell line","volume":"10","author":"Bens","year":"1999","journal-title":"J Am Soc Nephrol"},{"issue":"2","key":"2024053108512334300_pgae187-B64","doi-asserted-by":"crossref","first-page":"F495","DOI":"10.1152\/ajprenal.00521.2005","article-title":"Quantitative imaging of basic functions in renal (patho)physiology","volume":"291","author":"Kang","year":"2006","journal-title":"Am J Physiol Renal Physiol"},{"key":"2024053108512334300_pgae187-B65","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/bs.mcb.2019.04.013","article-title":"Novel fluorescence techniques to quantitate renal cell biology","volume":"154","author":"Shroff","year":"2019","journal-title":"Methods Cell Biol"},{"issue":"4","key":"2024053108512334300_pgae187-B66","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.biomaterials.2013.10.064","article-title":"Fibrin-binding, peptide amphiphile micelles for targeting glioblastoma","volume":"35","author":"Chung","year":"2014","journal-title":"Biomaterials"},{"issue":"3","key":"2024053108512334300_pgae187-B67","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1208\/s12248-010-9203-3","article-title":"The use of biorelevant dissolution media to forecast the in vivo performance of a drug","volume":"12","author":"Klein","year":"2010","journal-title":"AAPS J"},{"issue":"10","key":"2024053108512334300_pgae187-B68","doi-asserted-by":"crossref","first-page":"e0163063","DOI":"10.1371\/journal.pone.0163063","article-title":"An empirical biomarker-based calculator for cystic index in a model of autosomal recessive polycystic kidney disease-the Nieto\u2013Narayan formula","volume":"11","author":"Nieto","year":"2016","journal-title":"PLoS One"}],"container-title":["PNAS Nexus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/pnasnexus\/advance-article-pdf\/doi\/10.1093\/pnasnexus\/pgae187\/57501799\/pgae187.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/3\/5\/pgae187\/58004924\/pgae187.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/3\/5\/pgae187\/58004924\/pgae187.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T19:50:59Z","timestamp":1717185059000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article\/doi\/10.1093\/pnasnexus\/pgae187\/7668081"}},"subtitle":[],"editor":[{"given":"Dennis","family":"Discher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,30]]},"references-count":68,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,4,30]]}},"URL":"https:\/\/doi.org\/10.1093\/pnasnexus\/pgae187","relation":{},"ISSN":["2752-6542"],"issn-type":[{"value":"2752-6542","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5]]},"published":{"date-parts":[[2024,4,30]]},"article-number":"pgae187"}}