Magnetic Nanoparticles Directed Delivery of Berberine—A Cytotoxic Phytoceutical for Tumor Control

Iron oxide nanoparticles have attained importance in cancer therapy because of its magnetic property and biocompatibility. In the present work iron oxide nanoparticles (NP(s)) were complexed with a cytotoxic phytoceutical Berberine (BBN) and these complexes (NP-drug complexes) were targeted to the tumor site in mice bearing solid tumor on hind limbs by the application of an external magnetic field. The NPs were characterized by Fourier Transform Infra Red Spectroscopy (FTIR), X-ray Diffraction (XRD) and Transmission Electron microscopy (TEM). The mechanism of tumor regression was studied by monitoring tumor volume and comet assay. The expression levels of apoptotic genes were examined by both conventional and real time PCR. The morphological alterations of tissue ultra structure by Histopathological examination and blood and serum parameters of the treated animals were studied. The oral administration of NP-drug complexes along with external application of magnetic field resulted in significant reduction of tumor volume. The studies on both conventional and real time PCR revealed that the underlying molecular mechanism of the tumor regression was due to altered expression of the genes bax, bcl ₂, caspase 9, caspase 8 and caspase 3. The NP-drug complexes at the doses were found to be non-toxic as there was no change in the blood and serum biochemical parameters in the treated animals. Histopathological examinations indicated distinct alteration in the tumor tissues of treated animals while there was no change in normal tissues. The study suggests apoptosis through the intrinsic pathway could be the underlying mechanism of tumor regression by the magnetic NP directed delivery of BBN to the tumor cells.