A doxorubicin–platinum conjugate system: impacts on PI3K/AKT actuation and apoptosis in breast cancer cells

Abstract

In recent years, the development of a nano-conjugate system for drug delivery applications has gained attention among researchers. Keeping this in mind, in this study, we developed a doxorubicin-platinum conjugate system that targeted breast cancer cell lines. To achieve this, we developed platinum nanoparticles using polyvinylpyrrolidone (PVP). High resolution-transmission electron microscopy (HR-TEM) revealed the occurrence of octopod-shaped platinum nanoparticles. Subsequently, doxorubicin (DOX) was conjugated on the surface of the as-prepared platinum octopods <i>via</i> an <i>in situ</i> stirring method. The physicochemical characterization of the doxorubicin-platinum conjugate system revealed that the PVP of PtNPs interacts with the NH₂ group of doxorubicin <i>via</i> electrostatic interaction/hydrogen bonding. Besides, the doxorubicin-platinum conjugate system exhibited a sustained drug release profile within the cancer cells. Furthermore, the evaluation of the <i>in vitro</i> anticancer efficacy of the doxorubicin-platinum conjugate system in breast cancer cells (MCF-7 and MDA-MB-231) unveiled the induction of apoptosis <i>via</i> intracellular ROS and DNA damage, rather than free DOX and PtNPs. Remarkably, we also perceived that the doxorubicin-platinum conjugate system was strong enough to down-regulate the PI3K/AKT signalling pathway. As a result, the tumour suppressor gene <i>PTEN</i> was activated, which led to the stimulation of a mitochondrion-based intrinsic apoptotic pathway and its downstream caspases, triggering cell death. Hence, our findings suggested that a biologically stable doxorubicin-platinum conjugate system could be an imperative therapeutic agent for anticancer therapy in the near future.