Nanocomposites of iron oxide, sodium alginate, and eugenol induce apoptosis via PI3K/Akt/mTOR signaling in Hep3 cells and in vivo hepatotoxicity in the zebrafish model

Hepatic cancer is among the most recurrently detected malignancies worldwide and one of the main contributors
to cancer-associated mortality. With few available therapeutic choices, there is an instant necessity to explore
suitable options. In this aspect, Nanotechnology has been employed to explore prospective chemotherapeutic
approaches, especially for cancer treatment. Nanotechnology is concerned with the biological and physical
properties of nanoparticles in the therapeutic use of drugs. In the current work, formulation, and characterization
of α-Fe2O3–Sodium Alginate-Eugenol nanocomposites (FSE NCs) using several approaches like SEM and TEM,
UV–visible, FTIR, and PL spectroscopy, XRD, EDAX, and DLS studies have been performed. With an average size
of 50 nm, the rhombohedral structure of NCs was identified. Further, their anticancer activity against Hep3B
liver cancer cell lines has been performed by cell viability, dual staining, DCFH-DA, Annexin-V/-FITC/PI, cell
cycle analysis methods, and PI3K/Akt/mTOR signaling proteins were studied to assess the anticancer effects of
the NCs in Hep3B cells. Also, anti-cancer activity on animal modeling in-vivo using zebra fishes to hematological
parameters, liver enzymes, and histopathology study effectiveness was noticed. Moreover, the NCs reduced the
viability, elevated the ROS accumulation, diminished the membrane integrity, reduced the antioxidants, blocked
the cell cycle, and triggered the PI3K/Akt/mTOR signaling axis that eventually resulted in cell death. As a result,
FSE NCs possess huge potential for use as a possible anticancer candidate.