Bimetallic Au@Pd nanodendrite system incorporating multimodal intracellular imaging for improved doxorubicin antitumor efficiency

Abstract

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.

Keywords: 3D-CytoViva fluorescence analysis; Bimetallic nanodendrites; Doxorubicin; Hyperspectral imaging; Real-time apoptosis.