Herbometallic nano-drug inducing metastatic growth inhibition in breast cancer through intracellular energy depletion.

: Cancer cells need extensive energy supply for their uncontrolled cell division and metastasis which is exclusively dependent on neighboring cells, especially adipocytes. Herein, we have introduced a novel herbometallic nano-drug, Heerak Bhasma nanoparticle (HBNP) from natural resources showing high potential in the reduction of energy supply thereby promoting cell death in breast cancer cells. Inductively coupled plasma optical emission spectra (ICP-OES), atomic absorption spectra (AAS), Raman spectra, X-ray diffraction analyses confirmed the physicochemical properties of HBNP. The differential light scattering (DLS) and field emission scanning electron microscope (FESEM) analyzed the cell-permeable size of HBNP, whereas, cell viability assay confirmed the non-toxic effect. Seahorse energy efflux assay, apoptotic cell quantification, ROS, mitochondrial membrane potential, in vivo oxidative stress etc. were measured using standard protocol. The notable changes in cancer energy metabolism investigated by cellular Mito and Glyco-stress analyses confirmed the HBNP induced intracellular energy depletion. Also, a significant reduction in mitochondrial membrane potential and subsequently, extensive reactive oxygen species (ROS) generations were observed in presence of HBNP followed by the induction of cell apoptosis. The cell invasion and wound healing assay followed by reduced expression both protein (MMP 2, MMP 9) and cytokine (IL6, IL10) had signified the effectiveness of HBNP against cancer metastasis. In addition, HBNP also showed an excellent antitumor activity in vivo followed by developing healing characteristics due to oxidative stress. All these findings strongly suggest that HBNP has the potential to be the new cancer therapeutic. A schematic phenomenon represents the overall HBNP mediated anticancer activity via limitation of both fatty acid uptake and energy metabolism.