Abstract
Globally, cancer is the second most common cause of death, and Europe accounts for almost 25% of the global cancer burden, although its people make up only 10% of the world’s population. Conventional systemically administered anti-cancer drugs come with important drawbacks such as inefficiency due to poor bioavailability and improper biodistribution, severe side effects associated with low therapeutic indices, and the development of multidrug resistance. Therefore, smart nano-engineered targeted drug-delivery systems with tailored pharmacokinetics and biodistribution which can selectively deliver anti-cancer agents directly to the tumor site are the solution to most difficulties encountered with conventional therapeutic tools. Here, we report on the synthesis, physicochemical characterization, and in vitro evaluation of biocompatibility and anti-tumor activity of novel magnetically targetable SPIONs based on magnetite (Fe3O4) nanoparticles’ surface modified with β-cyclodextrin (CD) and paclitaxel (PTX)–guest–host inclusion complexes (Fe3O4@β-CD/PTX). Both pristine Fe3O4@β-CD nanopowders and PTX-loaded thin films fabricated by MAPLE technique were investigated. Pristine Fe3O4@β-CD and Fe3O4@β-CD/PTX thin films were physicochemically characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The biocompatibility of bare magnetic nanocomposite thin films was evaluated by MTT cell viability assay on a normal 3T3 osteoblast cell line culture and by measuring the level of NO in the culture medium. No significant modifications, neither in cell viability nor in NO level, could be observed, thereby demonstrating the excellent biocompatibility of the SPIONs thin films. Inverted phase-contrast microscopy showed no evident adverse effect on the morphology of normal osteoblasts. On the other hand, Fe3O4@β-CD/PTX films decreased the cell viability of the MG-63 osteosarcoma cell line by 85%, demonstrating excellent anti-tumor activity. The obtained results recommend these magnetic hybrid films as promising candidates for future delivery, and hyperthermia applications in cancer treatment.
Highlights
In a recent press release [1,2], the International Agency for Research on Cancer and the World Health Organization put cancer as the second leading cause of death globally, with an estimated 9.6 million deaths in 2018, while the global cancer burden has risen18.1 million new cases
We studied both nanopowder composites and thin films deposited by matrix-assisted pulsed laser evaporation (MAPLE)
The nanopowders were fully characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and thermal analysis (simultaneous thermogravimetric analysis (TGA) and dynamic scanning calorimetry (DSC)
Summary
Most of the new cases (23.4%) and deaths (20.3%) by cancer were registered in Europe. Most conventional medicines currently used in cancer treatment suffer some major drawbacks such as poor bioavailability associated with low water solubility, improper biodistribution, and lack of controlled, selective delivery to targeted disease areas resulting in a low therapeutic index, severe adverse effects, the development of multidrug resistance (MDR), and even treatment failure. Pharmaceutical nanotechnology provides powerful tools for circumventing these drawbacks by increasing drug bioavailability, prolonging drug circulation time, decreasing the clearance rate, and increasing drug stability in physiological media. Nanocarriers’ surfaces can be modified with targeting ligands which are guided by specific ligand–receptor interactions, allowing precise spatial control of nanocarrier localization within the body [3]. Smart nano-transporters can be engineered to trigger drug release in response to small microenvironmental changes in local pH, temperature, redox potential, and enzyme activity, as well as to remote, externally applied stimuli such as electric fields, laser pulses, ultrasounds, and magnetic fields [3,4,5]
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