{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:41:02Z","timestamp":1791236462880,"version":"4.1.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007479","name":"Fondazione Cassa di Risparmio di Padova e Rovigo","doi-asserted-by":"publisher","award":["Bando Ricerca Pediatrica 2012\/2014, grant #13\/09"],"award-info":[{"award-number":["Bando Ricerca Pediatrica 2012\/2014, grant #13\/09"]}],"id":[{"id":"10.13039\/100007479","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Brains for Brain Foundation\u2014Onlus"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0156452","type":"journal-article","created":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T17:48:17Z","timestamp":1464284897000},"page":"e0156452","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":88,"title":["Targeted Polymeric Nanoparticles for Brain Delivery of High Molecular Weight Molecules in Lysosomal Storage Disorders"],"prefix":"10.1371","volume":"11","author":[{"given":"Marika","family":"Salvalaio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rigon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Belletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"D\u2019Avanzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pederzoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Ruozi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriano","family":"Marin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Angela","family":"Vandelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Forni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Scarpa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosella","family":"Tomanin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Tosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,5,26]]},"reference":[{"key":"ref1","article-title":"Fabry Disease: Perspectives from 5 Years of FOS","author":"M Fuller","year":"2006"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1651-2227.2008.00660.x","article-title":"CNS-directed gene therapy for lysosomal storage diseases","volume":"97","author":"MS Sands","year":"2008","journal-title":"Acta Paediatr"},{"key":"ref3","first-page":"3421","article-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"EF Neufeld","year":"2001"},{"key":"ref4","article-title":"GeneReviews(R)","author":"LA Clarke","year":"1993"},{"key":"ref5","article-title":"GeneReviews(R)","author":"M Scarpa","year":"1993"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/0046-8177(95)90097-7","article-title":"Pathological findings in Gaucher disease type 2 patients following enzyme therapy","volume":"26","author":"KE Bove","year":"1995","journal-title":"Hum Pathol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1073\/pnas.91.6.2076","article-title":"Convection-enhanced delivery of macromolecules in the brain","volume":"91","author":"RH Bobo","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1227\/00006123-199604000-00024","article-title":"Increasing volume of distribution to the brain with interstitial infusion: dose, rather than convection, might be the most important factor","volume":"38","author":"RA Kroll","year":"1996","journal-title":"Neurosurgery"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"599","DOI":"10.3171\/jns.2000.92.4.0599","article-title":"<italic>In vivo<\/italic> assessment of the window of barrier opening after osmotic blood-brain barrier disruption in humans","volume":"92","author":"T Siegal","year":"2000","journal-title":"J Neurosurg"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.progpolymsci.2007.05.014","article-title":"Nanomedicine in the diagnosis and therapy of neurodegenerative disorders","volume":"32","author":"AV Kabanov","year":"2007","journal-title":"Prog Polym Sci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1517\/17425247.5.2.155","article-title":"Polymeric nanoparticles for the drug delivery to the central nervous system","volume":"5","author":"G Tosi","year":"2008","journal-title":"Expert Opin Drug Deliv"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.addr.2013.08.008","article-title":"Drug delivery to the central nervous system by polymeric nanoparticles: what do we know?","volume":"71","author":"J Kreuter","year":"2014","journal-title":"Adv Drug Deliv Rev"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jconrel.2011.08.017","article-title":"Transport of drugs across the blood-brain barrier by nanoparticles","volume":"161","author":"S Wohlfart","year":"2012","journal-title":"J Control Release"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jconrel.2013.11.023","article-title":"Insight on the fate of CNS-targeted nanoparticles. Part I: Rab5-dependent cell-specific uptake and distribution","volume":"174","author":"A Vilella","year":"2014","journal-title":"J Control Release"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jconrel.2014.01.004","article-title":"Insight on the fate of CNS-targeted nanoparticles. Part II: Intercellular neuronal cell-to-cell transport","volume":"177","author":"G Tosi","year":"2014","journal-title":"J Control Release"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.2217\/nnm.12.172","article-title":"Brain-targeted polymeric nanoparticles: <italic>in vivo<\/italic> evidence of different routes of administration in rodents","volume":"8","author":"G Tosi","year":"2013","journal-title":"Nanomedicine (Lond)"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2007.05.022","article-title":"Targeting the central nervous system: <italic>in vivo<\/italic> experiments with peptide-derivatized nanoparticles loaded with Loperamide and Rhodamine-123","volume":"122","author":"G Tosi","year":"2007","journal-title":"J Control Release"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2217\/nnm.11.11","article-title":"Investigation on mechanisms of glycopeptide nanoparticles for drug delivery across the blood-brain barrier","volume":"6","author":"G Tosi","year":"2011","journal-title":"Nanomedicine (Lond)"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.ijpharm.2014.05.054","article-title":"Characterization of lysosome-destabilizing DOPE\/PLGA nanoparticles designed for cytoplasmic drug release","volume":"471","author":"R Chhabra","year":"2014","journal-title":"Int J Pharm"},{"key":"ref20","unstructured":"Boyle J. BIND Therapeutics Reports Phase 2 Data from iNSITE 1 and iNSITE 2 Trials with BIND-014 and Provides Strategic Update. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/ir.bindtherapeutics.com\/releasedetail.cfm?ReleaseID=963798\" xlink:type=\"simple\">http:\/\/ir.bindtherapeutics.com\/releasedetail.cfm?ReleaseID=963798<\/ext-link>."},{"key":"ref21","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1586\/erm.09.15","article-title":"Current advances in research and clinical applications of PLGA-based nanotechnology","volume":"9","author":"JM Lu","year":"2009","journal-title":"Expert Rev Mol Diagn"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"6226","DOI":"10.1016\/j.biomaterials.2011.04.078","article-title":"Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles","volume":"32","author":"PM Valencia","year":"2011","journal-title":"Biomaterials"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.ijrobp.2013.02.009","article-title":"Preclinical evaluation of Genexol-PM, a nanoparticle formulation of paclitaxel, as a novel radiosensitizer for the treatment of non-small cell lung cancer","volume":"86","author":"ME Werner","year":"2013","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1073\/pnas.252784899","article-title":"Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB","volume":"100","author":"K Ohmi","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1002\/jgm.790","article-title":"Reduction of GAG storage in MPS II mouse model following implantation of encapsulated recombinant myoblasts","volume":"7","author":"A Friso","year":"2005","journal-title":"J Gene Med"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1093\/hmg\/ddl038","article-title":"Correction of Hunter syndrome in the MPSII mouse model by AAV2\/8-mediated gene delivery","volume":"15","author":"M Cardone","year":"2006","journal-title":"Hum Mol Genet"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1007\/s10545-007-0641-8","article-title":"The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome)","volume":"30","author":"AR Garcia","year":"2007","journal-title":"J Inherit Metab Dis"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1016\/j.biomaterials.2010.01.049","article-title":"PLGA nanoparticles surface decorated with the sialic acid, N-acetylneuraminic acid","volume":"31","author":"L Bondioli","year":"2010","journal-title":"Biomaterials"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.jconrel.2004.07.007","article-title":"Microparticle formation and its mechanism in single and double emulsion solvent evaporation","volume":"99","author":"ID Rosca","year":"2004","journal-title":"J Control Release"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.2174\/1871527313666140806145540","article-title":"Poly (D,L-lactide-co-glycolide) nanoparticles loaded with cerebrolysin display neuroprotective activity in a rat model of concussive head injury","volume":"13","author":"B Ruozi","year":"2014","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.ejpb.2004.04.006","article-title":"Poly(lactic acid) nanoparticles labeled with biologically active Neutravidin for active targeting","volume":"58","author":"L Nobs","year":"2004","journal-title":"Eur J Pharm Biopharm"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1208\/s12249-010-9382-3","article-title":"Freeze thaw: a simple approach for prediction of optimal cryoprotectant for freeze drying","volume":"11","author":"PV Date","year":"2010","journal-title":"AAPS PharmSciTech"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.biomaterials.2009.09.036","article-title":"Folic acid conjugated nanoparticles of mixed lipid monolayer shell and biodegradable polymer core for targeted delivery of Docetaxel","volume":"31","author":"Y Liu","year":"2010","journal-title":"Biomaterials"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s00702-010-0497-1","article-title":"NIR-labeled nanoparticles engineered for brain targeting: <italic>in vivo<\/italic> optical imaging application and fluorescent microscopy evidences","volume":"118","author":"G Tosi","year":"2011","journal-title":"J Neural Transm (Vienna)"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1602\/neurorx.2.1.3","article-title":"The blood-brain barrier: bottleneck in brain drug development","volume":"2","author":"WM Pardridge","year":"2005","journal-title":"NeuroRx"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1017\/S0031182011001119","article-title":"The loading of labelled antibody-engineered nanoparticles with Indinavir increases its <italic>in vitro<\/italic> efficacy against <italic>Cryptosporidium parvum<\/italic>","volume":"138","author":"L Bondioli","year":"2011","journal-title":"Parasitology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"e16601","DOI":"10.1371\/journal.pone.0016601","article-title":"Blood-brain barrier impairment in an animal model of MPS III B","volume":"6","author":"S Garbuzova-Davis","year":"2011","journal-title":"PLoS One"},{"key":"ref39","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2377-13-174","article-title":"Blood-brain barrier impairment in MPS III patients","volume":"13","author":"S Garbuzova-Davis","year":"2013","journal-title":"BMC Neurol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1073\/pnas.1222742110","article-title":"Engineering a lysosomal enzyme with a derivative of receptor-binding domain of apoE enables delivery across the blood-brain barrier","volume":"110","author":"D Wang","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1093\/brain\/awg089","article-title":"Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis","volume":"126","author":"M Jeyakumar","year":"2003","journal-title":"Brain"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1093\/brain\/aws095","article-title":"Contribution of brain inflammation to neuronal cell death in neuronopathic forms of Gaucher&apos;s disease","volume":"135","author":"EB Vitner","year":"2012","journal-title":"Brain"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.2174\/138161208784705504","article-title":"Lysosomal storage diseases and the blood-brain barrier","volume":"14","author":"DJ Begley","year":"2008","journal-title":"Curr Pharm Des"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0156452","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T07:18:03Z","timestamp":1589008683000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0156452"}},"subtitle":[],"editor":[{"given":"Valentin","family":"Ce\u00f1a","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,5,26]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2016,5,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0156452","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,26]]}}}