engleski

Transformations of L-DOPA during the synthesis of gold-based nanodelivery systems for LAT-1 targeting

LAT-1, the large neutral amino acid transporter-1, plays a crucial role in cancer growth and proliferation, making it a promising biomarker for imaging and treating human malignancies such as brain cancers. Thus, growing attention is being paid to the development of LAT-targeted drug delivery systems with blood-brain penetration ability [1, 2]. For this purpose, gold nanoparticles (AuNPs) functionalized with L-DOPA have been developed [1]. The great potential of such systems to be used in brain cancer therapy prompts the need for evaluation of the processes occurring at the nano-bio interface [3]. In the presence of gold salts, L-DOPA can undergo various transformations such as oxidation, cyclization, and polymerization [4]. To avoid binding structurally altered molecules to the nanosurface and prevent any negative impact on human health, it is important to consider these transformation patterns. This study aimed to investigate the behavior of L-DOPA upon interaction with a gold nanosurface by using a combination of nuclear magnetic resonance (NMR) spectroscopy and computational methods. Experimental results showed that the final form of L-DOPA on the AuNPs surface is dependent on the molar ratio of reactants used during synthesis. When there was an excess of L-DOPA compared to Au, no alterations in the structure of L-DOPA were observed. However, an excess of Au was found to promote the oxidation of L-DOPA, which could result in various oxidation products being bound to the gold nanosurface. NMR spectra revealed that L-DOPA underwent intramolecular cyclization but could not differentiate oxidation products. On the other hand, computational simulations using density functional theory (DFT) and molecular dynamics (MD) techniques identified the most probable oxidation products for binding to the AuNP surface. The highest affinity to gold nanosurface was obtained for dopachrome compared to its tautomer and leukodopachrome. The obtained results represent valuable mechanistic data about the binding events at the surface of AuNPs to encourage their application as a drug-delivery systems in cancer therapy

LAT1 ; gold nanoparticles ; L-DOPA ; drug-delivery nanosystem

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