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Evaluation of nano-bio interactions of doxorubicin-coated gold nanoparticles

Background: Nanomedicine is a rapidly evolving field that promises improved therapeutic efficacy and reduced toxicity of medicines. [1] Conjugation of a drug onto gold NPs (AuNPs) may alter the pharmacokinetics and pharmacodynamics and mediate its toxicity. [2] Doxorubicin (DOX), a cytotoxic drug with a broad antitumor activity, was used as model compound to test the nano-drug delivery system. The aim of the study was to investigate and compare nano-bio interactions of newly synthesized AuNPs stabilized with biocompatible polyethylene glycol (PEG) and functionalized with DOX (DOXAuNPs), and AuNPs just stabilized with PEG (PEGAuNPs) Experimental: Characterization and stability assessment of NPs included determination of size, size distribution, shape and zeta potential. Stability was evaluated in cell culture media(CCM) in the absence and presence of bovine serum albumin(BSA). Binding affinities and secondary changes in protein structure upon NPs and BSA interactions have been investigated using fluorescence quenching and circular dichroism (CD) methods. The uptake of the AuNPs was studied using confocal microscopy. Acellular reactive oxygen species (ROS) production was studied by the DCFH-DA assay. Results: Stability assessment showed increase in size and zeta potential for both types of NPs in CCM which indicated their destabilization. However, this was not observed in the presence of BSA due to formation of protein corona. Binding affinities were almost similar between BSA and both typed of NPs. However, PEGAuNPs caused the higher conformational changes in BSA compared to DOXAuNPs. The confocal microscopy images indicated stronger uptake of DOX-AuNPs compared to PEG-AuNPs. Finally, a dose-dependent ROS generation was determined for both NP types, with significantly larger effect shown in PEG-AuNPs. Conclusion: The prepared DOX-AuNPs maintain their stability in biomimetic media by associating with BSA, while minimally affecting its structure. They are successfully taken into cells, and show limited potential for oxidative stress. The results demonstrate good promise for their successful implementation as drug nanocarriers.

doxorubicin, gold nanoparticles, fluorescence spectroscopy, circular dichroism, confocal microscopy

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