Pro–apoptotic iron oxide nanosystems as selective anti – TB drugs

Simple item page
dc.contributor.advisorMalgas-Enus, Rehanaen_ZA
dc.contributor.advisorMavumengwana, Vuyoen_ZA
dc.contributor.authorJaffer, Shaakirahen_ZA
dc.contributor.otherStellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.en_ZA
dc.date.accessioned2024-03-04T13:55:28Zen_ZA
dc.date.accessioned2024-04-26T16:16:08Zen_ZA
dc.date.available2024-03-04T13:55:28Zen_ZA
dc.date.available2024-04-26T16:16:08Zen_ZA
dc.date.issued2024-03en_ZA
dc.descriptionThesis (MSc)--Stellenbosch University, 2024.en_ZA
dc.description.abstractENGLISH ABSTRACT: Tuberculosis (TB) is reportedly the biggest airborne disease, after covid-19, and amongst the top 10 causes of death worldwide. The disease is mainly prevalent in low- and middle-income countries and has financial and social impacts that negatively affect development in these countries. Consequently, addressing the implications of this disease is highly important. According to the World Health Organization (WHO), approximately a third of the world’s population is infected with TB. TB is transmitted by inhaling a droplet of Mycobacterium tuberculosis (M. tuberculosis), it remains within the body as its latent form. However, it takes a weak immune system to activate the latent form to become active TB. With current treatments showing a moderate to high success rate, the duration of treatment which causes toxicity, and drug resistance are issues that are faced TB treatment. Treatment spans between 6 to 24 months depending on case severity, with accompanying acute side effects. Therefore, the purpose of this study was to investigate functionalized iron oxide nanoparticles and their efficacy as antimycobacterial agents. The synthesized bare iron oxide nanoparticles include magnetite (Fe3O4), ferrous oxide (FeO) and ferric oxide (Fe2O3) nanoparticles and were modified using compounds that are known to activate apoptosis including, 1,3,5-triaza-7-phosphaadamantane (PTA), 3,3′,3″-phosphanetriyltris (benzenesulfonic acid) trisodium salt (TPPTS), 9-β-D-arabinofuranosyl guanine hydrate (ara-g hydrate), 2,3-diphenylbenzo[g]quinoxaline-5,10-dione (DPBQ) and 4,5,6,7- tetrahydro-5,5,7,7-tetramethyl-2-[[(5-nitro-2-thienyl) carbonyl]amino]-thieno[2,3-c]pyridine-3- carboxylic acid ethyl ester (NPC -26). Characterization techniques included, fourier transform infrared spectroscopy (FT–IR), ultraviolet – visible spectroscopy (UV-Vis) and high-resolution transmission electron microscopy (HR-TEM) on the synthesized and modified nanoparticles. The selected bare nanoparticles and modified nanoparticles were tested for antimycobacterial activity against Mycobacterium smegmatis (M. smegmatis), frequently used to emulate M. tuberculosis due to its non-infectious attributes. Interestingly, both the bare and modified nanoparticles noticeably promoted growth of M. smegmatis in a dose dependent manner at all concentrations tested ranging from 250 to 1,95 µg/mL. A rapid uptake effect on iron oxide nanoparticles by M. smegmatis caused an exponential increase in bacterial growth, indicating that the bacterium itself was able to metabolize both the bare and modified nanoparticles synthesized in this study. The dose dependant results indicated a notable affinity of mycobacteria for the bare iron oxide nanoparticles, suggesting a high binding capability and implicating a potential role of iron acquisition mechanisms in the pathogenesis or survival strategies of mycobacteria. The iron oxide nano system that piqued interest was magnetite + NPC-26 which showed a degree of potential at the lowest concentration of 1,95 µg/mL. The dosage effect of this concentration showed a more progressive growth curve showing inhibition of the bacterial growth over the 5-day test period. Thus, the cells uptake of the magnetite was due to an affinity for iron and the NPC-26 inhibiting cell growth to some extent. The study set out to synthesize three variations of iron oxide nanoparticles with the intent to capitalize on the distinctive properties of iron oxide nanoparticles to allow for precise drug delivery to the site of infection. Further modifying the nanoparticles with apoptotic-inducing drugs to enhance the efficacy of treatment by promoting programmed cell death in infected cells and accelerating the clearance of the pathogen. The utilization of magnetite loaded with NPC-26 demonstrated a noteworthy inhibitory effect on the growth of mycobacteria, as indicated by the dosage effect experimental results. Therefore, the utilization of the iron oxide nanoparticles modified with apoptotic-inducing abilities may have significant promise as a novel and targeted approach for the treatment of tuberculosis.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Tuberkulose (TB) is na bewering die grootste aansteeklike siekte, ná covid-19, en is deel van die top 10 oorsake van dood wêreldwyd. Die siekte is hoofsaaklik teenwoordig in lae- en middel inkomste-lande en het finansiële en sosiale implikasies wat ontwikkeling in hierdie lande negatief beïnvloed. Daarom is dit van groot belang om die effek van hierdie siekte te verlaag. Volgens die Wêreld Gesondheids Organisasie (WGO) is ongeveer 'n derde van die wêreld bevolking geïnfekteer met TB. TB word oorgedra deur die inaseming van lug druppels wat met Mycobacterium tuberculosis (M. tuberculosis) besmet is en bly in die liggaam as 'n latente vorm. Dit neem egter 'n swak immuunstelsel om van die latente na aktiewe TB gaan. Met huidige behandelings tegnieke wat 'n matige tot hoë sukses koers toon, is die duur van behandeling 'n probleem wat hoë hoeveelhede toksisiteit in die pasiënt veroorsaak, en weerstandig bakterieë te weeg bring. Behandeling strek van 6 tot 24 maande, afhangende van die erns van die gevalle, met gepaardgaande akute newe-effekte. Daarom was die doel van hierdie studie om gefunksionaliseerde ysteroksied nanodeeltjies en hul effektiwiteit as antimikrobakteriële middels te ondersoek. Die gesintetiseerde naakte ysteroksied nanodeeltjies sluit in magnetiet (Fe3O4), ysteroksied (FeO) en ferris oksied (Fe2O3) nanodeeltjies en is gewysig met verbindings wat bekend is om apoptose te aktiveer, insluitende 1,3,5-triaza-7-fosfaadamantaan (PTA), 3,3',3"-Fosfantriieltris (bensoeensulfonsuur) trinatriumsout (TPPTS), 9-β-D-Arabinofuranosiel guanienhidraat (ara-g hidraat), 2,3-difenielbenso[g]kwinoxaal-5,10-dioon (DPBQ) en 4,5,6,7-Tetrahidro-5,5,7,7-tetrametiel-2-[[[5- nitro-2-thieniel) karboniel]amino]-thieno[2,3-c]piridiene-3-karboksielsuuretielester (NPC-26) is gebruik. Karakteriserings metodes wat vierier-transform-infrarooispektroskopie (FT-IR), ultravioletsigbare spektroskopie (UV-Vis) en hoë-resolusie-transmissie-elektronmikroskopie (HR-TEM) ingesluit het, is op al die gesintetiseerde en gewysigde nanodeeltjies gedoen. Die gekose blote nanodeeltjies en gewysigde nanodeeltjies is getoets vir antimikobakteriële aktiwiteit teen Mycobacterium smegmatis (M. smegmatis), wat dikwels gebruik word om M. tuberculosis na te boots as gevolg van sy nie-infektiewe eienskappe. Interessant genoeg het beide die blote en gewysigde nanodeeltjies opvallend die groei van M. smegmatis bevorder op 'n dosisafhanklike wyse by alle getoetste konsentrasies van 250 tot 1,95 µg/mL. 'n Vinnige opname-effek van ysteroksied-nanodeeltjies deur M. smegmatis het 'n eksponensiële toename in bakteriële groei veroorsaak, wat aandui dat die bakterium self in staat was om beide die blote en gewysigde nanodeeltjies wat in hierdie studie gesintetiseer is, te metaboliseer. Die dosisafhanklike resultate het op 'n merkbare affiniteit van mikobakterieë vir die blote ysteroksied-nanodeeltjies gedui, wat 'n hoë bindingsvermoë suggereer en 'n potensiële rol van ysterverkrygingsmeganismes in die patogenese of oorlewingstrategieë van mikobakterieë impliseer. Die ysteroksied-nano-stelsel wat belangstelling gewek het, was magnetiet + NPC-26 wat 'n mate van potensiaal getoon het teen die laagste konsentrasie van 1,95 µg/mL. Die dosiseffek van hierdie konsentrasie het 'n meer progressiewe groeikurwe getoon met inhibisie van die bakteriële groei oor die 5-dag toetsperiode. Die opname van die magnetiet deur die selle te wyte aan 'n affiniteit vir yster, en die NPC-26 het die selgroei tot op 'n mate geïnhibeer. Die studie het ten doel gehad om drie variasies van ysteroksied-nanodeeltjies te sintetiseer, deur gebruik te maak van die kenmerkende eienskappe van ysteroksied-nanodeeltjies en sodoende akkurate dwelmtoediening na die infeksieplek toe te laat. Verdere modifikasie van die nanodeeltjies met apoptose-induserende dwelms het die doeltreffendheid van behandeling verhoog deur geprogrammeerde selsterfte in geïnfekteerde selle te bevorder en die vinnige opruiming van die patogeen te bespoedig. Die gebruik van magnetiet belaai met NPC-26 het 'n merkbare inhiberende effek op die groei van mikobakterieë getoon, soos aangedui deur die dosis-effek eksperimentele resultate. Dus het die gebruik van die ysteroksied-nanodeeltjies gemodifiseer met apoptose-induserende vermoëns 'n beduidende belofte as 'n nuwe en doelgerigte benadering vir die behandeling van tuberkuloseaf_ZA
dc.description.versionMastersen_ZA
dc.format.extentxii, 92 pages : illustrationsen_ZA
dc.identifier.urihttps://scholar.sun.ac.za/handle/10019.1/130401en_ZA
dc.language.isoen_ZAen_ZA
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subject.lcshMycobacterium tuberculosis -- Pathogenesisen_ZA
dc.subject.lcshFerric oxide -- Synthesisen_ZA
dc.subject.lcshDrug delivery systemsen_ZA
dc.subject.lcshApoptosisen_ZA
dc.titlePro–apoptotic iron oxide nanosystems as selective anti – TB drugsen_ZA
dc.typeThesisen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
jaffer_pro_2024.pdf
Size:
5.32 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Masters Degrees (Chemistry and Polymer Science)