2024
IL-1β Induces Human Endothelial Surface Expression of IL-15 by Relieving let-7c-3p Suppression of Protein Translation.
Mullan C, Summer L, Lopez-Giraldez F, Tobiasova Z, Manes T, Yasothan S, Song G, Jane-Wit D, Saltzman W, Pober J. IL-1β Induces Human Endothelial Surface Expression of IL-15 by Relieving let-7c-3p Suppression of Protein Translation. The Journal Of Immunology 2024, 213: 1338-1348. PMID: 39302113, PMCID: PMC11493510, DOI: 10.4049/jimmunol.2400331.Peer-Reviewed Original ResearchIL-15Surface expressionIL-1BIL-15 transcriptsEndothelial cellsCD8 T cell activationExpression of IL-15EC surface expressionIL-15 transpresentationComplement activationGraft endothelial cellsActivity of CTLT cell activationIL-15 mRNAEndothelial surface expressionAbsence of complement activationCultured human endothelial cellsIL-1-mediated activationIL-15RAProtein translationAllograft rejectionRNA polymerase II-mediated transcriptionHuman endothelial cellsSuppression of protein translation285 Development of an electrochemiluminescence CFTR immunoassay
Browne J, Lee J, Peterec K, Garrison A, Bruscia E, Saltzman W, Egan M. 285 Development of an electrochemiluminescence CFTR immunoassay. Journal Of Cystic Fibrosis 2024, 23: s152. DOI: 10.1016/s1569-1993(24)01125-1.Peer-Reviewed Original Research264 Poly(amine-co-ester) nanoparticle delivery of CFTR mRNA shows restoration of CFTR activity in cystic fibrosis airway models
Garrison A, Lee J, Browne J, Akhtar L, Peterec K, Suberi A, Eaton D, Ene M, Zhang X, Whang C, Oez H, Kizilirmak T, Bruscia E, Piotrowski-Daspit A, Saltzman W, Egan M. 264 Poly(amine-co-ester) nanoparticle delivery of CFTR mRNA shows restoration of CFTR activity in cystic fibrosis airway models. Journal Of Cystic Fibrosis 2024, 23: s140-s141. DOI: 10.1016/s1569-1993(24)01104-4.Peer-Reviewed Original Research295 Polymeric nanoparticles for in utero gene delivery in non-human primates
Piotrowski-Daspit A, Lynn A, Eaton D, Bracaglia L, Mortlock R, Tarantal A, Glazer P, Saltzman W. 295 Polymeric nanoparticles for in utero gene delivery in non-human primates. Journal Of Cystic Fibrosis 2024, 23: s157. DOI: 10.1016/s1569-1993(24)01135-4.Peer-Reviewed Original ResearchEnhanced intratumoral delivery of immunomodulator MPLA via hyperbranched polyglycerol-coated biodegradable nanoparticles
Chang J, Shin K, Lewis J, Suh H, Lee J, Damsky W, Xu S, Bosenberg M, Saltzman W, Girardi M. Enhanced intratumoral delivery of immunomodulator MPLA via hyperbranched polyglycerol-coated biodegradable nanoparticles. Journal Of Investigative Dermatology 2024 PMID: 39122142, DOI: 10.1016/j.jid.2024.07.019.Peer-Reviewed Original ResearchMonophosphoryl lipid ATumor microenvironmentImmunomodulatory agentsStimulation of anti-tumor immune responseEfficacy of monophosphoryl lipid AT-helper (Th)1 responsesAnti-tumor immune responseTumor-draining lymph nodesToxicity associated with systemic administrationImmune responseModel of malignant melanomaAgonist monophosphoryl lipid ABiodegradable nanoparticlesImmunogenic tumor microenvironmentAntitumor immune responseDraining lymph nodesSystemic side effectsNatural killer cellsGradual drug releaseKiller cellsAntitumor efficacyMalignant melanomaImproved survivalLymph nodesChemotherapeutic agentsNext generation triplex-forming PNAs for site-specific genome editing of the F508del CFTR mutation
Gupta A, Barone C, Quijano E, Piotrowski-Daspit A, Perera J, Riccardi A, Jamali H, Turchick A, Zao W, Saltzman W, Glazer P, Egan M. Next generation triplex-forming PNAs for site-specific genome editing of the F508del CFTR mutation. Journal Of Cystic Fibrosis 2024 PMID: 39107154, DOI: 10.1016/j.jcf.2024.07.009.Peer-Reviewed Original ResearchCystic fibrosis transmembrane conductance regulatorCystic fibrosis transmembrane conductance regulator geneF508del-CFTR mutationPeptide nucleic acidCFBE cellsBronchial epithelial cellsCystic fibrosisTriplex-forming peptide nucleic acidsDonor DNACFTR mutationsEpithelial cellsCFTR functionMutations associated with genetic diseasesPrimary nasal epithelial cellsAnalysis of genomic DNAGenetic diseasesIncreased CFTR functionDevelopment of peptide nucleic acidsImprove CFTR functionTransmembrane conductance regulatorAutosomal recessive genetic diseaseNasal epithelial cellsAir-liquid interfaceCystic fibrosis bronchial epithelial cellsHuman bronchial epithelial cellsBranching in poly(amine-co-ester) polyplexes impacts mRNA transfection
Shin K, Suh H, Suberi A, Whang C, Ene M, Grundler J, Grun M, Saltzman W. Branching in poly(amine-co-ester) polyplexes impacts mRNA transfection. Biomaterials 2024, 311: 122692. PMID: 38986360, PMCID: PMC11298310, DOI: 10.1016/j.biomaterials.2024.122692.Peer-Reviewed Original ResearchPolymer branchingTransfection in vivoPhysicochemical propertiesPoly(amine-co-esterMRNA deliveryTerminal groupsPolymer featuresIn vitroPolymerNucleic acid deliveryMonomer compositionAnalysis of physicochemical propertiesStructural parametersCationic polymersStability of polyplexesMRNA transfectionTransfection efficiencyAcid deliveryDelivery vehiclesTransfectionMRNAModifying the Backbone Chemistry of PEG‐Based Bottlebrush Block Copolymers for the Formation of Long‐Circulating Nanoparticles
Grundler J, Whang C, Shin K, Savan N, Zhong M, Saltzman W. Modifying the Backbone Chemistry of PEG‐Based Bottlebrush Block Copolymers for the Formation of Long‐Circulating Nanoparticles. Advanced Healthcare Materials 2024, 13: e2304040. PMID: 38734871, PMCID: PMC11368614, DOI: 10.1002/adhm.202304040.Peer-Reviewed Original ResearchBottlebrush block copolymersPerformance of nanoparticlesBottlebrush polymersBlock copolymersBiomedical applicationsLinear hydrophilic polymersBackbone chemistryLocation of functional groupsPoly(lactic acidBottlebrush backboneNanoparticle shellHydrophilic polymersPolymer backboneSurface functionalizationHeterobifunctional poly(ethylene glycolPoly(ethylene glycolHierarchical controlBlood circulation half-livesEnhanced tumor accumulationNanoparticlesPolymerReduced cellular uptakeNanoparticle physicochemical propertiesBottlebrushConventional nanoparticlesEnhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys
Piotrowski-Daspit A, Bracaglia L, Eaton D, Richfield O, Binns T, Albert C, Gould J, Mortlock R, Egan M, Pober J, Saltzman W. Enhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys. Nature Communications 2024, 15: 4247. PMID: 38762483, PMCID: PMC11102454, DOI: 10.1038/s41467-024-48442-7.Peer-Reviewed Original ResearchConceptsPoly(amine-co-esterPolymer nanoparticlesDelivery of nucleic acid therapeuticsCell-type tropismTissue tropismNucleic acid delivery vehiclesIn vivo deliveryIn vivo efficacyCirculation half-lifeNucleic acid therapeuticsVehicle characteristicsTunable propertiesBiodistribution assessmentPhysiological fatePolymer chemistrySurface propertiesPharmacokinetic modelTissue targetingNanoparticlesDistribution modifiersPolymeric nanoparticlesTropismPolymerDelivery vehiclesHalf-lifePilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation
Grun M, Honhar P, Wang Y, Rossano S, Khang M, Suh H, Fowles K, Kliman H, Cavaliere A, Carson R, Marquez‐Nostra B, Saltzman W. Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation. Bioengineering & Translational Medicine 2024, 9: e10661. PMID: 39553429, PMCID: PMC11561825, DOI: 10.1002/btm2.10661.Peer-Reviewed Original ResearchVaginal dosage formsBioadhesive nanoparticlesCynomolgus monkeysAnalysis of inflammatory biomarkersVaginal microbicidesVaginal canalMultiple dosesInflammatory biomarkersTherapeutic efficacyVaginal fluidSystemic circulationLong-term deliveryNoninvasive imagingClinical translationDosage formsNon-human primatesDelivery vehiclesMonkeysDeliveryVaginitisUterusMicrobicidesSafety evaluationBiodistributionDoseExploiting Metabolic Defects in Glioma with Nanoparticle-Encapsulated NAMPT Inhibitors
Murray M, Noronha K, Wang Y, Friedman A, Paradkar S, Suh H, Sundaram R, Brenner C, Saltzman W, Bindra R. Exploiting Metabolic Defects in Glioma with Nanoparticle-Encapsulated NAMPT Inhibitors. Molecular Cancer Therapeutics 2024, 23: 1176-1187. PMID: 38691846, PMCID: PMC11292319, DOI: 10.1158/1535-7163.mct-24-0012.Peer-Reviewed Original ResearchConvection-enhanced deliveryCentral nervous systemTreatment of primary central nervous systemPrimary central nervous systemSustained drug release in vitroTumor growth delayAssociated with lower survival ratesBone marrow suppressionComplex mutational profilesNAMPT inhibitorsRelease in vitroIntracranial GBM xenograftsBlood-brain barrierDrug release in vitroRetinal toxicityMarrow suppressionNAMPTiGrowth delayTherapeutic vulnerabilitiesExtended survivalLow survival rateGBM xenograftsMutation profilesPromoter methylationAnticancer activity in vitroThe Technical and Ethical Framework of Fetal Therapy: Past and Current Advances
Lynn A, Glazer P, Saltzman W, Stitelman D. The Technical and Ethical Framework of Fetal Therapy: Past and Current Advances. Current Stem Cell Reports 2024, 10: 30-36. DOI: 10.1007/s40778-024-00235-w.Peer-Reviewed Original ResearchFetal drug deliverySuccess of nanomedicineDrug deliveryPharmacological drug treatmentsMinimally invasive strategyFetal therapyFetal applicationsClinical studiesCongenital diseaseInvasive strategyDrug treatmentClinical translationClinical practiceTherapyMedical interventionsDeliveryFetalNanomedicineBirthDiseaseFindingsACliniciansCompartmentalized ocular lymphatic system mediates eye–brain immunity
Yin X, Zhang S, Lee J, Dong H, Mourgkos G, Terwilliger G, Kraus A, Geraldo L, Poulet M, Fischer S, Zhou T, Mohammed F, Zhou J, Wang Y, Malloy S, Rohner N, Sharma L, Salinas I, Eichmann A, Thomas J, Saltzman W, Huttner A, Zeiss C, Ring A, Iwasaki A, Song E. Compartmentalized ocular lymphatic system mediates eye–brain immunity. Nature 2024, 628: 204-211. PMID: 38418880, PMCID: PMC10990932, DOI: 10.1038/s41586-024-07130-8.Peer-Reviewed Original ResearchResponse to herpes simplex virusCentral nervous systemImmune response to herpes simplex virusPosterior eyeImmune responseTherapeutic immune responsesOptic nerve sheathCervical lymph nodesAdeno-associated virusCNS diseaseDeep cervical lymph nodesHerpes simplex virusImmune protected miceCentral nervous system tissueLymphatic drainage systemImmunological featuresAnatomical extensionNerve sheathOptic nerveGene therapyLymph nodesMultiple dosesSimplex virusLymphatic circuitLymphatic signalNanoscale Surface Topography of Polyethylene Glycol-Coated Nanoparticles Composed of Bottlebrush Block Copolymers Prolongs Systemic Circulation and Enhances Tumor Uptake
Grundler J, Shin K, Suh H, Whang C, Fulgoni G, Pierce R, Saltzman W. Nanoscale Surface Topography of Polyethylene Glycol-Coated Nanoparticles Composed of Bottlebrush Block Copolymers Prolongs Systemic Circulation and Enhances Tumor Uptake. ACS Nano 2024, 18: 2815-2827. PMID: 38227820, DOI: 10.1021/acsnano.3c05921.Peer-Reviewed Original ResearchConceptsBottlebrush block copolymersSurface topographyBlock copolymersPoly(ethylene glycolClinical translation of nanomedicinePEGylated nanoparticlesEnhanced tumor uptakeNanoscale surface topographyTranslation of nanomedicinesRough surface topographyLinear block copolymersProlonged systemic circulationPerformance of nanocarriersPolymer coatingNanoparticle coatingSmooth surfaced nanoparticlesTumor uptakeTumor accumulationBiomedical applicationsNanoparticle formulationSystemic circulationClinical translationTumor extravasationNanoparticlesCoating
2023
MODL-02. DEVELOPMENT OF RODENT GLIOBLASTOMA MODELS OF MGMT-MEDIATED TEMOZOLOMIDE RESISTANCE
Lee T, Bhatt D, Sundaram R, Saltzman W, Bindra R, Vasquez J. MODL-02. DEVELOPMENT OF RODENT GLIOBLASTOMA MODELS OF MGMT-MEDIATED TEMOZOLOMIDE RESISTANCE. Neuro-Oncology 2023, 25: v298-v298. PMCID: PMC10640218, DOI: 10.1093/neuonc/noad179.1153.Peer-Reviewed Original ResearchMouse glioma modelPotential therapeutic targetMGMT overexpressionGlioma modelTherapeutic targetTumor growthDaily x 5 daysMGMT expressionMGMT inhibitorsUseful preclinical toolTumor immune microenvironmentImportant prognostic biomarkerFischer 344 ratsHuman GBM cell linesDelays tumor growthHigh MGMT expressionMouse glioma cellsRodent glioblastoma modelsSyngeneic Fischer 344 ratsGBM cell linesAlkylator therapyO6-methylguanine-DNA methyltransferaseChemoimmunotherapy combinationImmune microenvironmentSyngeneic model