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

Puja Patel, Devan Umapathy, Selvambigai Manivannan, Vinita Manimaran Nadar, Rajiu Venkatesan, Velanganni Antony , Joseph Arokiyam, Srinivasan Pappu, Kumar Ponnuchamy

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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 via an in situ stirring method. The physicochemical characterization of the doxorubicin–platinum conjugate system revealed that the PVP of PtNPs interacts with the NH2 group of doxorubicin via 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 in vitro anticancer efficacy of the doxorubicin–platinum conjugate system in breast cancer cells (MCF-7 and MDA-MB-231) unveiled the induction of apoptosis via 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 PTEN 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.

Original languageEnglish
Pages (from-to)4818-4828
JournalRSC Advances
Volume11
DOIs
Publication statusPublished - 25 Jan 2021

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