CHITOSAN AND CARBOXYMETHYL CHITOSAN (CMC)-COATED MAGNETITE NANOPARTICLES FOR DRUG DELIVERY TO CANCER CELLS: EFFECT OF MOLECULAR WEIGHT ON DRUG RELEASE

Novel effective delivery systems for chemotherapeutic drugs are of utmost demand in nanomedicine. Herein, we prepared magnetite (Fe₃O₄) nanoparticles (NPs) coated with either low molecular (LM) or high molecular (HM) weight Chitosan or Carboxymethyl Chitosan (CMC) and assessed their drug loading and release efficiencies. Chitosan/CMC-coated MNPs were fully characterized by various physiochemical techniques including TEM, XRD, DLS, FTIR, and VSM. These techniques clearly elucidated the nanostructure, morphology, surface charge, and magnetization of all functional MNPs. We then loaded them with the anticancer drug Dox to achieve biocompatible, biodegradable, and pH-responsive drug nanocarriers. Drug release was evaluated at both neutral and acidic pH to mimic endosomal/lysosomal conditions. HM Chitosan-NPs or CMC-NPs showed faster and more sustained controlled release (~ 90 – 99%) at acidic pH, while LM NPs exhibited slightly lower drug release (~ 60 – 65%). Notably, almost negligible release was found at neutral physiological pH for all MNP formulations, which is crucial for successful pH-triggered delivery system. The delivery of Dox using CMC-NPs was then evaluated in human monocytic leukemia THP-1 cancer cells. Remarkably, while the unloaded CMC-NPs were non-toxic to the tested cell lines, Dox@CMC-MNPs were found to be highly potent causing apoptotic cell death to cancer cells (IC₅₀ = 16 µg/mL), as evident from live confocal images. These results show great promise for the utilization of Chitosan/CMC-MNPs for potential in-vivo cancer theranostics.