Type: Article
Advanced Postsynthetic Modification of COF: Elevating Hydrophilicity for Efficient Doxorubicin Delivery
Journal: ACS Applied Bio Materials (25766422)Year: 2025Volume: Issue: 5Pages: 4325 - 4336
Asadi P. Mokhtari N. Asghari S. Rha H. Khodarahmi G. Jalali H. Sharma A. Dinari M. Kim J.S. Varshosaz J.Goshadrou A.a Hassanzadeh F.
DOI:10.1021/acsabm.5c00436Language: English
Abstract
Covalent organic frameworks (COFs) show great potential as drug delivery systems (DDSs) due to their customizable structures, stability, and capacity for pore surface functionalization. However, their natural hydrophobicity limits their dispersion in water, posing challenges for biological applications. We address this issue by initially reducing a COF (Az-COF) to an amine-linked form (Az-AL-COF) and subsequently sulfonating it to obtain Az-AL-SO3H-COF, a water-dispersible derivative. Water contact angle (WCA) analysis confirmed increased hydrophilicity across the series of 84.5, 61.2, and 54.7° for Az-COF, Az-AL-COF, and Az-AL-SO3H-COF, respectively. Using doxorubicin (Dox) as a model drug, the modified COFs exhibited pH-sensitive drug release, with greater release at acidic pH (5.6) compared to neutral pH (7.4). Cytotoxicity assays revealed that Az-AL-SO3H-COF was biocompatible with normal cells (MCF-10) while effectively suppressing the growth of cancer cells (MDA-MB-231). The Dox-loaded sulfonated COF (Dox@Az-AL-SO3H-COF) showed selective cytotoxicity against cancer cells, highlighting its potential as a pH-responsive, biocompatible DDS for cancer treatment. © 2025 American Chemical Society.
Author Keywords
covalent organic frameworkscytotoxicitydoxorubicindrug delivery systemshydrophilicityHepG2HT-29IrinotecanmicellePEGPLGAretinoic acid5-FUAsialoglycoprotein receptorsGalactosylated NLCsHepatocellular carcinomaLactobionic acidHepG2HT-29IrinotecanmicellePEGPLGAretinoic acid5-FUAsialoglycoprotein receptorsGalactosylated NLCsHepatocellular carcinomaLactobionic acidAlkaline pretreatmentBioethanolEnzymatic hydrolysisMucor hiemalisSimons’ stainTobacco product wasteGlycyrrhiza Glabra ResiduePhosphoric Acid PretreatmentSimons' StainSurfactant
Other Keywords
Antibiotics, AntineoplasticAntineoplastic AgentsBiocompatible MaterialsCell ProliferationCell SurvivalDoxorubicinDrug CarriersDrug Delivery SystemsDrug LiberationDrug Screening Assays, AntitumorHumansHydrogen-Ion ConcentrationHydrophobic and Hydrophilic InteractionsMaterials TestingMetal-Organic FrameworksMolecular StructureParticle SizeSurface PropertiesTargeted drug deliveryantineoplastic agentantineoplastic antibioticbiomaterialdoxorubicindrug carriermetal organic frameworkCancer cellsCovalent organic frameworksCustomizableDoxorubicinDrug-delivery systemsNatural hydrophobicityPore surfacePostsynthetic modificationStructure stabilitySurface Functionalizationcell proliferationcell survivalchemical phenomenachemical structurechemistrydrug delivery systemdrug effectdrug releasedrug screeninghumanmaterials testingparticle sizepHsurface propertysynthesisControlled drug deliveryCamptothecinCarcinoma, HepatocellularCell Line, TumorDrug CarriersDrug Delivery SystemsHep G2 CellsHT29 CellsHumansLactic AcidLiver NeoplasmsMicellesNanoparticlesParticle SizePolyethylene GlycolsPolyglactin 910Polyglycolic AcidTretinoindrug carrieririnotecanmacrogolpolyglactinretinoic acidnanoparticlepoly(lactic-glycolic acid)-poly(ethyleneglycol) copolymerpolylactic acid-polyglycolic acid copolymerArticlecell structurechemical bindingchemical parameterscolorectal cancercritical micelle concentrationcytotoxicitydispersitydrug delivery systemdrug mechanismdrug releaseentrapment efficiencyfluorescence spectroscopyHep-G2 cell lineHT-29 cell linehumanhuman cellin vitro studyinfrared radiationliver cell carcinomamean release timemicellepolymerizationpriority journalproductivityproton nuclear magnetic resonancezeta potentialanalogs and derivativeschemistryliver tumorprocedurestumor cell lineAntibiotics, AntineoplasticApoptosisChondroitin SulfatesDiffusionDoxorubicinDrug CompoundingMolecular Targeted TherapyNanocapsulesPolyelectrolytesTreatment OutcomeDifferential scanning calorimetryFourier transform infrared spectroscopyHigh resolution transmission electron microscopyTransmission electron microscopyantineoplastic antibioticchondroitin sulfatenanocapsulepolyelectrolyteAsialoglycoprotein receptorsGelatin nanoparticlesHepatocellular carcinomaNano particulatesParticles sizesPolyelectrolyte complexesRelease EfficiencyTargeted deliverydrug effectsdrug formulationmolecularly targeted therapyultrastructureTargeted drug deliveryAcetoneAminesAntineoplastic AgentsAsialoglycoprotein ReceptorDelayed-Action PreparationsDisaccharidesFlow CytometryFluorouracilGalactoseGlyceridesMagnetic Resonance SpectroscopyOleic AcidPolysorbatesSpectroscopy, Fourier Transform InfraredSurface PropertiesTetrazolium SaltsThiazolesToxicity Tests3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromidedecanoic acidgalactosylated nanostructured lipid carrierglycerol stearatelabrafaclactobionic acidoctadecylamineoctanoic acidphosphatidylcholinepolysorbate 80propidium iodidesolutol hs 15soy lecithin s100unclassified drugaqueous solutioncell strain HepG2chemical reactionconcentration responseconjugateconjugationcontrolled drug releasecontrolled release formulationcontrolled studydrug cytotoxicityemulsionencapsulationinfrared spectroscopyliposomal deliveryCamptothecinCarcinoma, HepatocellularCell Line, TumorDrug CarriersDrug Delivery SystemsHep G2 CellsHT29 CellsHumansLactic AcidLiver NeoplasmsMicellesNanoparticlesParticle SizePolyethylene GlycolsPolyglactin 910Polyglycolic AcidTretinoindrug carrieririnotecanmacrogolpolyglactinretinoic acidnanoparticlepoly(lactic-glycolic acid)-poly(ethyleneglycol) copolymerpolylactic acid-polyglycolic acid copolymerArticlecell structurechemical bindingchemical parameterscolorectal cancercritical micelle concentrationcytotoxicitydispersitydrug delivery systemdrug mechanismdrug releaseentrapment efficiencyfluorescence spectroscopyHep-G2 cell lineHT-29 cell linehumanhuman cellin vitro studyinfrared radiationliver cell carcinomamean release timemicellepolymerizationpriority journalproductivityproton nuclear magnetic resonancezeta potentialanalogs and derivativeschemistryliver tumorprocedurestumor cell lineAntibiotics, AntineoplasticApoptosisChondroitin SulfatesDiffusionDoxorubicinDrug CompoundingMolecular Targeted TherapyNanocapsulesPolyelectrolytesTreatment OutcomeDifferential scanning calorimetryFourier transform infrared spectroscopyHigh resolution transmission electron microscopyTransmission electron microscopyantineoplastic antibioticchondroitin sulfatenanocapsulepolyelectrolyteAsialoglycoprotein receptorsGelatin nanoparticlesHepatocellular carcinomaNano particulatesParticles sizesPolyelectrolyte complexesRelease EfficiencyTargeted deliverydrug effectsdrug formulationmolecularly targeted therapyultrastructureTargeted drug deliveryAcetoneAminesAntineoplastic AgentsAsialoglycoprotein ReceptorDelayed-Action PreparationsDisaccharidesFlow CytometryFluorouracilGalactoseGlyceridesMagnetic Resonance SpectroscopyOleic AcidPolysorbatesSpectroscopy, Fourier Transform InfraredSurface PropertiesTetrazolium SaltsThiazolesToxicity Tests3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromidedecanoic acidgalactosylated nanostructured lipid carrierglycerol stearatelabrafaclactobionic acidoctadecylamineoctanoic acidphosphatidylcholinepolysorbate 80propidium iodidesolutol hs 15soy lecithin s100unclassified drugaqueous solutioncell strain HepG2chemical reactionconcentration responseconjugateconjugationcontrolled drug releasecontrolled release formulationcontrolled studydrug cytotoxicityemulsionencapsulationinfrared spectroscopyliposomal deliveryDecodingAmplify and forwardAmplify-and-forward relayingCognitive radio networkDecode - and - forwardsOutage performanceSecondary networksSpectrum leasingsTransmission ratesCognitive radioAdaptive algorithmsBudget controlComplex networksComputational complexityFrequency division multiple accessNonlinear programmingOrthogonal frequency division multiplexingResource allocationComputationally efficientInterference constraintsMixed-integer nonlinear programmingNetwork throughputNumber of iterationsOrthogonal frequency division multiple accessThroughput maximisationAnatomyEthanolFermentationSodium HydroxideTobaccoWaterWettabilityBioethanolHydrophilicityMorphologyAccessible surface areasAlkaline pretreatmentBio-ethanol productionCrystalline structureMucor hiemalisSeparate hydrolysis and fermentationSodium hydroxide pretreatmentSurface hydrophilicityEnzymatic hydrolysis