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Evaluation of selenium funcationalised gold nanocomposites (Au@G-Se-Se-G)


Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. Challenges associated with therapeutic modalities involve the diffusion constraints of the blood-brain barrier (BBB). Limitations associated with conventional treatment necessitate the development of alternative approaches for radiotherapy adjuvant drugs. Selenium functionalised gold nanocomposites were synthesised and optmised. To decorate Au nanoparticles with diselenide (-Se-Se-), firstly, diselenide functionalized gelatin (G-Se-Se-G) was prepared by covalently conjugating gelatin with diselenodipropionic acid through EDC/NHS coupling chemistry and subsequently used to replace citrate from AuNP surface, thus obtaining Au@G-Se-Se-G NPs. Au@G-Se-Se-G NPs were of spherical morphology with an average size of about 15 nm and were characterized by TEM, EDS, Raman spectra, DLS, FTIR, CV and CD. Later, Au@G-Se-Se-G's radiosensitizing effect on LN229 cells was investigated. The cells were subjected to γ-radiation (4 Gy) in combination with either Au@G-Se-Se-G (2 nM) or Au@G (2 nM). The findings showed that radiation exposure alone caused a 50% reduction in LN229 cell survival and the combination of drug and radiation together lead to significant reduction in survival fraction by 75%. The study to determine the Au@G-Se-Se-G dose modification factor for radiosensitizing activity in glioblastoma cells and the in-vivo pharmacokinetics, biodistribution and toxicity is under underway. Together, the above results establish an in-house shape and size selective selenium functionalised gold nanoparticles and that selenium functionalization of gold nanoparticles is an effective strategy to achieve radio-sensitization in the cellular models of GBM. Validation of the above results shall be confirmed using mouse models of GBM.

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