6533b851fe1ef96bd12a8dfa

RESEARCH PRODUCT

Synthetic/ECM-inspired hybrid platform for hollow microcarriers with ROS-triggered nanoporation hallmarks

Paolo ContessottoSiti Afifah IsmailAbhay PanditGesmi MilcovichGrazia Marsico

subject

biomedical applicationsPathologyresponsivenessPolymersNanoparticlecardiomyocytes02 engineering and technologyMatrix metalloproteinaseMicroscopy Atomic Force01 natural sciencesreleaseHollow spheresExtracellular matrixDrug Delivery Systemsreactive oxygenCytotoxicitynanomaterialsdegradationchemistry.chemical_classificationDrug CarriersMicroscopyMultidisciplinaryIschemic conditionsQRAtomic ForcePolymerStimuli-responsive021001 nanoscience & nanotechnologyMicrospheresDrug deliveryMedicineROS (Reactive Oxygen Species) inflamed tissue stimuli-responsive biomaterials ischemic conditions hollow spheres polysulfides collagenCollagenhypoxia-reoxygenationdelivery0210 nano-technologyAnimals; Cell Line; Drug Carriers; Drug Delivery Systems; Matrix Metalloproteinases; Microscopy Atomic Force; Microspheres; Polymers; Rats; Reactive Oxygen Speciesmedicine.medical_specialtyROS (Reactive Oxygen Species)ScienceInflamed tissue010402 general chemistryArticleCell LineBiomaterialsPolysulfidesmedicineAnimalsReactive oxygen speciesMicrocarrierMatrix Metalloproteinases0104 chemical sciencesRatschemistrySettore CHIM/09 - Farmaceutico Tecnologico ApplicativoBiophysicsnanoparticlesReactive Oxygen Species

description

Reactive oxygen species (ROS) are key pathological signals expressed in inflammatory diseases such as cancer, ischemic conditions and atherosclerosis. An ideal drug delivery system should not only be responsive to these signals but also should not elicit an unfavourable host response. This study presents an innovative platform for drug delivery where a natural/synthetic composite system composed of collagen type I and a synthesized polythioether, ensures a dual stimuli-responsive behaviour. Collagen type I is an extracellular matrix constituent protein, responsive to matrix metalloproteinases (MMP) cleavage per se. Polythioethers are stable synthetic polymers characterized by the presence of sulphur, which undergoes a ROS-responsive swelling switch. A polythioether was synthesised, functionalized and tested for cytotoxicity. Optimal conditions to fabricate a composite natural/synthetic hollow sphere construct were optimised by a template-based method. Collagen-polythioether hollow spheres were fabricated, revealing uniform size and ROS-triggered nanoporation features. Cellular metabolic activity of H9C2 cardiomyoblasts remained unaffected upon exposure to the spheres. Our natural/synthetic hollow microspheres exhibit the potential for use as a pathological stimuli-responsive reservoir system for applications in inflammatory diseases. This material is based upon works supported by the European Union funding under the AngioMatTrain 7th Framework Programme, Grant Agreement Number 317304. This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grant Number 13/RC/2073. The authors acknowledge the use of the facilities and the scientific and technical assistance of the Centre for Microscopy and Imaging at the National University of Ireland Galway (www.imagingnuigalway.ie), a facility that is co-funded by the Irish Government’s Programme for Research in Third Level Institutions, Cycles 4 and 5, National Development Plan 2007–2013. peer-reviewed

10.1038/s41598-017-13744-yhttp://hdl.handle.net/11577/3459828