Hybrid Nanocomposite of Imidazolium Based Chitosan and Anderson-type Manganese Polyoxomolybdate for Boosting Drug Delivery Against Breast Cancer

Abstract

Polyoxometalates (POMs) are a class of inorganic cytotoxic agents with potential anticancer effects. As the nano-formulation is one of the best approaches to adjust the therapeutic effects along with selective delivery, in this study, a novel biocompatible nano-composite (NC) of Anderson-type manganese polyoxomolybdate (MnMo6) was prepared using chitosan conjugate to achieve better selective cytotoxicity profile.Imidazolium modified chitosan (CSIm) was utilizedto getthe MnMo6 hybridNCs (MnMo6@CSIm NCs).The best resulting NCs were evaluated for their anticancer activity against breast cancer cell lines (MCF-7 & MDA-MB-231) as well as HUVEC normal cells using MTT assay. Furthermore, cellular uptake, apoptosis ratio and cell migration inhibition were evaluated on the MDA-MB-231 cell line as the triple-negative aggressive cell line.The optimized NPs had a zeta potential above +27 mV with a uniform distribution of sizes around 145 nm. The loading content and release efficiency were both satisfying (about 44% and 98%). In the release study, a pH-responsive release was detectedcomparing the neutral conditions.The NCs had a better anticancer activity than free MnMo6 in both cancer cell lines, without detectable cytotoxicity against HUVEC normal cells. The cellular uptake was about 100 %, and apoptosis value was enough high (81%) compared to free MnMo6. Interestingly, the MnMo6 hybrid NCs inhibitedthe cell migration of MDA-MB-231 cell line1.5 times better than the free MnMo6. All of these results are fascinating to follow more pre-clinical studies on this hybrid NC.

Chitosan–Imidazolium Core–Shell Nanoparticles of Gd-Mn-Mo Polyoxometalate as Novel Potential MRI Nano-Agent for Breast Cancer Detection

“…According to the HNMR, the shell signals around 7.5 and 8.7 ppm proved the presence of the imidazolium aromatic features of CSIm. That is in agreement with the previous study [20].…”

“…Based on the obtained results, POM@CSIm NPs induced RBC hemolysis below 4%, suggesting POM@CSIm NPs for a wide safety margin in blood-contact applications and suitability for intravenous administration. Mahvash et al [20] reported the same results for Anderson-type manganese polyoxomolybdate entrapped in a CSIm shell.…”

“…The resulting mixture was stirred for 48 h at 75 • C. When the reaction was completed, the product precipitates were obtained by adding ethanol to the reaction mixture. In the next step, it was washed with anhydrous ethanol and dried under vacuum at 80 • C. The chemical structure of this conjugate was confirmed by FTIR, XRD, and 1 HNMR spectra [20,23].…”

“…To prepare the control (complete hemolysis, 100%) and negative control (no hemolysis, 0%), 1 mL of RBC suspension was mixed with 1 mL of deionized water and 0.9% NaCl isotonic solution, respectively. After 4 incubations at 37 ± 1 • C, with shaking, in a water bath, the tubes were centrifuged at 3000 rpm for 5 min, and the absorbance of the supernatant was determined by UV-visible spectroscopy at a 540 wavelength [20]. Finally, the hemolysis percentage of the samples was calculated using the following equation:…”

“…Imidazolium-modified chitosan (CSIm) is one of those polymeric scaffolds used before as a potential carrier for POMs [20]. Therefore, coating polyoxometalates with CSIm leads to a higher coating efficiency than chitosan alone.…”