Bimetallic Au@Pd nanodendrite system incorporating multimodal intracellular imaging for improved doxorubicin antitumor efficiency Adewale Oladipo 1 and Sogolo Lebelo 1 and Titus A.M. Msagati 2 1 Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Science Park Florida, Johannesburg 1710, South Africa 2 Institute for Nanotechnology and Water Sustainability (iNanoWS), College of Science, Engineering and Technology, University of South Africa, Science Park Florida, Johannesburg 1710, South Africa The sufficient accumulation of drugs is crucial for efficient treatment in a complex tumor microenvironment. Drug delivery systems (DDS) with high surface area and selective cytotoxicity present a novel approach to mitigate insufficient drug loading for improved therapeutic response. Herein, a doxorubicin-conjugated bimetallic gold-core palladium-shell nanocarrier with multiple dense arrays of branches (Au@PdNDs.PEG/DOX) was characterized and its efficacy against breast adenocarcinoma (MCF-7) and lung adenocarcinoma (A549) cells were evaluated. Enhanced darkfield and hyperspectral imaging (HSI) microscopy were used to study the intracellular uptake and accumulation of the DOX-loaded nanodendrites A fascinating data from a 3D-CytoViva fluorescence imaging technique provided information about the dynamics of localization and distribution of the nanocarrier. In vitro cytotoxicity assays indicated that Au@PdNDs.PEG/DOX inhibited the proliferative effects of MCF-7 cells at equivalent IC50 dosage compared to DOX alone. The nanocarrier triggered higher induction of apoptosis proved by a time-dependent phosphatidylserine V release, cell cycle arrest, and flow cytometry analysis. Moreover, the cell cycle phase proportion increase suggests that the enhanced apoptotic effect induced by Au@PdNDs. PEG/DOX was via a G2/M phase arrest. Thus, this study demonstrated the potential of dendritic nanoparticles to improve DOX therapeutic efficiency and plasmonic-mediated intracellular imaging as a suitable theranostic platform for deployment in nanomedicine.
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