2023
Intrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma
Khang M, Lee J, Lee T, Suh H, Lee S, Cavaliere A, Rushing A, Geraldo L, Belitzky E, Rossano S, de Feyter H, Shin K, Huttner A, Roussel M, Thomas J, Carson R, Marquez-Nostra B, Bindra R, Saltzman W. Intrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma. Science Translational Medicine 2023, 15: eadi1617. PMID: 37910601, PMCID: PMC11078331, DOI: 10.1126/scitranslmed.adi1617.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidDelivery of drugsEffective therapyTherapeutic indexPARP inhibitorsBlood-brain barrierSite of tumorRapid systemic clearanceXenograft mouse modelSolvent evaporation processAdministration of substancesLeptomeningeal spreadIntrathecal deliveryLeptomeningeal metastasesBrain penetrationSystemic clearanceTumor regressionPolymer nanoparticlesMetastatic medulloblastomaMouse modelPediatric medulloblastomaDrug accumulationCSF turnoverEncapsulated drugsPET imagingAnti-seed PNAs targeting multiple oncomiRs for brain tumor therapy
Wang Y, Malik S, Suh H, Xiao Y, Deng Y, Fan R, Huttner A, Bindra R, Singh V, Saltzman W, Bahal R. Anti-seed PNAs targeting multiple oncomiRs for brain tumor therapy. Science Advances 2023, 9: eabq7459. PMID: 36753549, PMCID: PMC9908025, DOI: 10.1126/sciadv.abq7459.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainBrain NeoplasmsCell Line, TumorGlioblastomaMiceNanoparticlesPeptide Nucleic AcidsTemozolomideConceptsConvection-enhanced deliveryHigh recurrence rateOrthotopic mouse modelBrain tumor therapyTreatment of glioblastomaRecurrence ratePoor survivalLethal malignancyMouse modelGBM progressionTumor cellsGlioblastomaTumor therapyBioadhesive nanoparticlesOncomiRSurvivalTreatmentSeed regionMalignancyTemozolomideTherapy
2021
Nanoparticle-mediated convection-enhanced delivery of a DNA intercalator to gliomas circumvents temozolomide resistance
Wang Y, Jiang Y, Wei D, Singh P, Yu Y, Lee T, Zhang L, Mandl HK, Piotrowski-Daspit AS, Chen X, Li F, Li X, Cheng Y, Josowitz A, Yang F, Zhao Y, Wang F, Zhao Z, Huttner A, Bindra RS, Xiao H, Mark Saltzman W. Nanoparticle-mediated convection-enhanced delivery of a DNA intercalator to gliomas circumvents temozolomide resistance. Nature Biomedical Engineering 2021, 5: 1048-1058. PMID: 34045730, PMCID: PMC8497438, DOI: 10.1038/s41551-021-00728-7.Peer-Reviewed Original ResearchConceptsConvection-enhanced deliveryPatient-derived xenograftsTMZ-resistant gliomasTMZ-resistant cellsGlioma cell linesSurvival benefitTemozolomide resistanceChemotherapeutic temozolomideDetectable toxicityTemozolomideOxaliplatin prodrugHuman glioblastomaGenome-wide RNA profilingTranslational strategiesDrugsCell linesGliomasAnticancer drugsMetabolomic analysisGlioblastomaDeliveryDistinct mechanismsRNA profilingMetabolic pathwaysPatients
2017
Surface chemistry governs cellular tropism of nanoparticles in the brain
Song E, Gaudin A, King AR, Seo YE, Suh HW, Deng Y, Cui J, Tietjen GT, Huttner A, Saltzman WM. Surface chemistry governs cellular tropism of nanoparticles in the brain. Nature Communications 2017, 8: 15322. PMID: 28524852, PMCID: PMC5454541, DOI: 10.1038/ncomms15322.Peer-Reviewed Original ResearchConceptsSurface chemistryDifferent surface chemistriesDrug deliveryNanoparticlesNanoparticle designChemistryTherapeutic efficacyAssociation rateFunctionalizationCentral nervous systemConvection-enhanced deliverySignificant uptakeBrain interstitiumOrthotopic modelNervous systemNeurological diseasesAdverse toxicityCellular tropismExtent of internalizationCellular depositionBrainCell populationsDepositionPropertiesGlioblastoma
2016
Distribution of polymer nanoparticles by convection-enhanced delivery to brain tumors
Saucier-Sawyer JK, Seo YE, Gaudin A, Quijano E, Song E, Sawyer AJ, Deng Y, Huttner A, Saltzman WM. Distribution of polymer nanoparticles by convection-enhanced delivery to brain tumors. Journal Of Controlled Release 2016, 232: 103-112. PMID: 27063424, PMCID: PMC4893898, DOI: 10.1016/j.jconrel.2016.04.006.Peer-Reviewed Original ResearchConceptsConvection-enhanced deliveryBlood-brain barrierBrain-penetrating nanoparticlesIntracranial tumorsBrain tumorsGlioblastoma multiformeHealthy brainMain tumor massFatal brain tumorPresence of tumorBrain tumor treatmentLocal recurrenceInfusion sitePeritumoral tissuesTumor massCED infusionIndividual tumorsTumorsNecrotic regionsTumor treatmentLocal administrationHeterogeneous distribution patternAdministrationBrainCell targeting
2014
Imaging the delivery of brain-penetrating PLGA nanoparticles in the brain using magnetic resonance
Strohbehn G, Coman D, Han L, Ragheb RR, Fahmy TM, Huttner AJ, Hyder F, Piepmeier JM, Saltzman WM, Zhou J. Imaging the delivery of brain-penetrating PLGA nanoparticles in the brain using magnetic resonance. Journal Of Neuro-Oncology 2014, 121: 441-449. PMID: 25403507, PMCID: PMC4323763, DOI: 10.1007/s11060-014-1658-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBrain NeoplasmsConvectionDrug Delivery SystemsFerric CompoundsGlioblastomaHumansImage Processing, Computer-AssistedLactic AcidMagnetic Resonance ImagingNanoparticlesNeuroimagingPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerRatsRats, Sprague-DawleyConceptsBrain-penetrating nanoparticlesSuperparamagnetic iron oxideEfficient deliveryDrug-loaded nanoparticlesDistribution of nanoparticlesTransverse relaxivityPLGA nanoparticlesNanoparticlesConvection-enhanced deliveryDelivery platformFuture clinical applicationsUniversal tumor recurrenceClinical translationSignal attenuationDetection modalitiesIron oxideSame morphologyParticle distributionDeliveryGroundbreaking approachClinical applicationRelevant volumesRelaxivityTreatment of GBMOxide
2013
Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma
Zhou J, Patel TR, Sirianni RW, Strohbehn G, Zheng MQ, Duong N, Schafbauer T, Huttner AJ, Huang Y, Carson RE, Zhang Y, Sullivan DJ, Piepmeier JM, Saltzman WM. Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 11751-11756. PMID: 23818631, PMCID: PMC3718184, DOI: 10.1073/pnas.1304504110.Peer-Reviewed Original Research