Sachin Haresh Bhagchandani
he/him/his
Postdoctoral AssociateAbout
Research
Publications
2025
Antibody–bottlebrush prodrug conjugates for targeted cancer therapy
Liu B, Nguyen H, Jiang Y, Wang A, Lensch V, Sun Z, Boyer Z, Raftopoulos P, Dai Y, MacNicol P, Wang Y, Jyotsana N, Wang W, Bhagchandani S, Hemdev S, Shieh P, Kristufek S, Boucher M, Downes M, Evans R, MacMillan D, Johnson J. Antibody–bottlebrush prodrug conjugates for targeted cancer therapy. Nature Biotechnology 2025, 1-12. PMID: 40925997, PMCID: PMC12425459, DOI: 10.1038/s41587-025-02772-z.Peer-Reviewed Original ResearchAntibody-drug conjugatesProdrug conjugatesHER2-targeting antibody-drug conjugateDrug mechanismsTargeted cancer therapyDrug-to-antibody ratioDrug mechanism of actionIgG1 monoclonal antibodyMechanism of actionTumor modelCancer therapyTargeted therapeuticsClinical translationMonoclonal antibodiesTraditional antibody-drug conjugateCell uptakeTarget engagementA mechanically resilient soft hydrogel improves drug delivery for treating post-traumatic osteoarthritis in physically active joints
Joshi N, Yan J, Dang M, Slaughter K, Wang Y, Wu D, Ung T, Bhingaradiya N, Pandya V, Chen M, Kaur S, Bhagchandani S, Alfassam H, Joseph J, Gao J, Dewani M, Chu R, Yip R, Weldon E, Shah P, Pisal N, Shukla C, Sherman N, Luo J, Conway T, Eickhoff J, Botelho L, Alhasan A, Karp J, Ermann J. A mechanically resilient soft hydrogel improves drug delivery for treating post-traumatic osteoarthritis in physically active joints. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2409729122. PMID: 40163719, PMCID: PMC12002200, DOI: 10.1073/pnas.2409729122.Peer-Reviewed Original ResearchConceptsTreat post-traumatic osteoarthritisMechanical loadingSoft hydrogelsDrug releaseKinetics of drug releaseIntra-articular drug deliveryPost-traumatic osteoarthritisHydrogel potentialIntra-articular deliverySoft materialsHydrogelsDrug deliveryReduced cartilage degenerationSelf-HealingMouse knee jointsRelease kineticsCartilage degenerationActive jointsLoadSuperior performanceStructural integrityEncapsulated drugJointsDisease-modifying osteoarthritis drugsKnee joint
2024
Two-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response
Bhagchandani S, Yang L, Lam J, Maiorino L, Ben-Akiva E, Rodrigues K, Romanov A, Suh H, Aung A, Wu S, Wadhera A, Chakraborty A, Irvine D. Two-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response. Science Immunology 2024, 9: eadl3755-eadl3755. PMID: 39303017, PMCID: PMC11492009, DOI: 10.1126/sciimmunol.adl3755.Peer-Reviewed Original ResearchConceptsDendritic cellsGerminal centersHumoral immunityAntigen-specific germinal centerGerminal center responseSubunit vaccineFollicular dendritic cellsPrimary immune responseIncreased TrDose 7 daysPrime immunizationGC responseImmune responseVaccine deliveryCenter responseAdministered vaccinesImmunityVaccineRegimensAdjuvant vaccineDoseCellsHIVResponseBolusCarbohydrate-Lectin Interactions Reprogram Dendritic Cells to Promote Type 1 Anti-Tumor Immunity
Lensch V, Gabba A, Hincapie R, Bhagchandani S, Basak A, Alam M, Noble J, Irvine D, Shalek A, Johnson J, Finn M, Kiessling L. Carbohydrate-Lectin Interactions Reprogram Dendritic Cells to Promote Type 1 Anti-Tumor Immunity. ACS Nano 2024, 18: 26770-26783. PMID: 39283240, PMCID: PMC11646345, DOI: 10.1021/acsnano.4c07360.Peer-Reviewed Original ResearchCellular immunityDendritic cellsToll-like receptorsVirus-like particlesCD8+ T cellsTumor-specific cellular immunityVaccine developmentCancer vaccine developmentInfiltrate solid tumorsMurine melanoma modelT cell functionInhibited tumor growthActivate TLR signalingTumor controlCancer immunotherapyCD4+Melanoma modelTLR7 agonistDC activationT cellsSolid tumorsTumor cellsTumor growthHumoral immunityVLP platform
2023
Mixing ligands to enhance gas uptake in polyMOFs
Pearson M, Bhagchandani S, Dincă M, Johnson J. Mixing ligands to enhance gas uptake in polyMOFs. Molecular Systems Design & Engineering 2023, 8: 591-597. DOI: 10.1039/d2me00227b.Peer-Reviewed Original ResearchPolymer ligandsCO 2 uptakeTunable surface areaSurface areaMixed ligand approachSmall molecule componentsDistinct MOFsPolymeric ligandMOF latticeOrganic frameworksPolymer linkersTraditional MOFsPolyMOFsHybrid materialsFree linkersMOF-5Polymer incorporationLigand approachGas uptakeMOFMolecule componentsLigandsLinkerComplex architectureHereinEngineering kinetics of TLR7/8 agonist release from bottlebrush prodrugs enables tumor-focused immune stimulation
Bhagchandani S, Vohidov F, Milling L, Tong E, Brown C, Ramseier M, Liu B, Fessenden T, Nguyen H, Kiel G, Won L, Langer R, Spranger S, Shalek A, Irvine D, Johnson J. Engineering kinetics of TLR7/8 agonist release from bottlebrush prodrugs enables tumor-focused immune stimulation. Science Advances 2023, 9: eadg2239. PMID: 37075115, PMCID: PMC10115420, DOI: 10.1126/sciadv.adg2239.Peer-Reviewed Original ResearchConceptsToll-like receptor 7Cancer immunotherapyImmune stimulationMouse syngeneic tumor modelsNext-generation cancer immunotherapyImmune-related toxicitiesAcute systemic inflammationInnate immune cellsSyngeneic tumor modelsPotential cancer immunotherapySystemic inflammationImmune cellsReceptor 7Systemic administrationIntravenous administrationMyeloid cellsTumor growthSystemic toxicityTumor modelObservable systemic toxicityPotent stimulationImidazoquinolinesImmunotherapyStimulationProdrugMolecular bottlebrush prodrugs as mono- and triplex combination therapies for multiple myeloma
Detappe A, Nguyen H, Jiang Y, Agius M, Wang W, Mathieu C, Su N, Kristufek S, Lundberg D, Bhagchandani S, Ghobrial I, Ghoroghchian P, Johnson J. Molecular bottlebrush prodrugs as mono- and triplex combination therapies for multiple myeloma. Nature Nanotechnology 2023, 18: 184-192. PMID: 36702954, PMCID: PMC10032145, DOI: 10.1038/s41565-022-01310-1.Peer-Reviewed Original ResearchConceptsCombination therapyMultiple myelomaNarrow therapeutic indexMultiple myeloma therapyFree drug combinationFree drug counterpartsMyeloma therapySame doseTherapeutic indexTumor progressionBPD exhibitTherapyProteasome inhibitorsCombination nanomedicinesCancer therapyMonotherapyMyelomaSynergistic ratio
2022
STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity
Dane E, Belessiotis-Richards A, Backlund C, Wang J, Hidaka K, Milling L, Bhagchandani S, Melo M, Wu S, Li N, Donahue N, Ni K, Ma L, Okaniwa M, Stevens M, Alexander-Katz A, Irvine D. STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity. Nature Materials 2022, 21: 710-720. PMID: 35606429, PMCID: PMC9156412, DOI: 10.1038/s41563-022-01251-z.Peer-Reviewed Original ResearchConceptsSTING agonistsRobust T cell activationInnate immune stimulatorsT cell activationTumor rechallengeAnticancer immunityDendritic cellsAgonist deliverySingle doseCyclic dinucleotidesTumor antigensImmune stimulatorImmune memorySolid tumorsEnhanced immunotherapySystemic deliveryTumorsTumor cellsCancer cellsAgonistsImmunityDeliveryCellsActivationCleavable linker
2021
766 Toward safe, systemic delivery of synthetic TLR7/8 agonists using Bottlebrush Prodrugs (BPDs)
Bhagchandani S, Milling L, Liu B, Fessenden T, Spranger S, Johnson J, Irvine D. 766 Toward safe, systemic delivery of synthetic TLR7/8 agonists using Bottlebrush Prodrugs (BPDs). Journal For ImmunoTherapy Of Cancer 2021, 9: a801-a801. DOI: 10.1136/jitc-2021-sitc2021.766.Peer-Reviewed Original ResearchTLR reporter cellsSystemic deliveryAnti-PD-1 antibody treatmentMC38 colon cancer modelImidazoquinoline derivativesToll-like receptor agonistsSerum cytokine levelsMaximum tolerable doseSystemic side effectsImproved survival ratesReporter cellsAnti-tumor efficacyColon cancer modelCytokine levelsMetastatic diseaseTLR agonistsTLR7/8 agonistAntibody treatmentTLR activationTreatment of cancerTolerable doseReceptor agonistIntravenous administrationTopical solutionSide effectsEvolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants
Bhagchandani S, Johnson J, Irvine D. Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants. Advanced Drug Delivery Reviews 2021, 175: 113803. PMID: 34058283, PMCID: PMC9003539, DOI: 10.1016/j.addr.2021.05.013.Peer-Reviewed Original ResearchConceptsVaccine adjuvantsImidazoquinoline derivativesToll-like receptor 7Candidate vaccine adjuvantsSkin cancer treatmentBroad therapeutic utilityTLR7 toleranceTopical antiviralsImmunomodulatory agentsReceptor 7Systemic administrationPoor pharmacokinetic propertiesTherapeutic utilitySuccessful clinical translationSynthetic agonistsAntiviral formulationsInfectious diseasesPharmacokinetic propertiesCancer treatmentBroad expression profileAdjuvantClinical translationBiodistributionExpression profilesTherapeutics