Polysaccharide-based magnetic nanocomposites as drug carriers for potential colorectal cancer treatment

Abstract

Colorectal cancer is one of the most diagnosed malignant diseases in the world. The green-based, multifunctional, and highly biocompatible polysaccharide-based magnetic nanocomposites (PMNCs) as smart drug carriers can satisfy targeted cancer treatments to circumvent off-target cytotoxicity from conventional chemotherapy. This comprehensive research has sought to introduce five different green-based 5-Fluorouracil (5-FU) drug carriers, including Fe3O4 nanoparticles stabilized with Punica granatum fruit peel extract (Fe3O4/P. granatum/5-FU), rice straw cellulose fiber (CF/5-FU), magnetic cellulose fiber (MC/5-FU), cellulose nanocrystals (CNC/5-FU), and chitosan-coated magnetic CNC (CH/MCNC/5-FU) bionanocomposites. For this aim, spherical Fe3O4 nanoparticles was produced by a facile co-precipitation technique and using four different weight percentages of Punica granatum fruit peel extract as a green stabilizer. Then, the rod-shaped CF was isolated from rice straw waste by employing bleaching and alkali treatments. Fe3O4 nanoparticles were supported onto the CF matrix to fabricate MC nanoocmposites. The needle-like CNC was isolated from rice straw cellulose by the acid hydrolysis process. In addition, the ionic gelation method and the sodium tripolyphosphate cross-linker were used to fabricate layer-by-layer bionanocomposites of CH/MCNC/5-FU. The successful fabrication of the samples with desired physiochemical properties was indicated by X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersion X-ray spectroscopy (EDX), dynamic light scattering (DLS), thermogravimetric analysis (TGA), vibrating-sample magnetometry (VSM) of the swelling analysis, and ultraviolet-visible (UV) spectroscopy. The use of 2 weight % extract as stabilizer and capping agent appropriately decreased the size of spherical Fe3O4 NPs with enhanced stability and anticancer effects. Compared to CF/5-FU formulation, CNC/5-FU showed higher crystallinity, smaller size, and prolonged drug release at targeted pH media. The PMNCs samples of MC/5-FU and CH/MCNC/5-FU showed multifunctional physiochemical properties and also magnetic and heat-responsive manner. The use of chitosan coating in CH/MCNC/5-FU improved drug encapsulation efficiency and controlled drug release at various pH and heat induction conditions. From images of TEM and SEM, the size of all the synthesized samples was estimated to be below 80 nm, showing their potential usage in nanodrug delivery systems. In in vitro anticancer assay, the fabricated Fe3O4/P. granatum/5-FU, CF/5-FU, and CNC/5-FU desirably exhibited negligible damage against CCD112 normal cells and appropriate anticancer actions against HCT116 colorectal cancer cells. MC/5-FU with magnetic targeting and heat induction improved the anticancer effects, guide ability, and tolerable toxicity in targeted drug delivery systems. Further, CH/MCNC/5-FU showed not only high biocompatibility but also caused enhanced selectivity and elimination of the cancer cells. In conclusion, the fabricated the fabricated Fe3O4 nanoparticles, polysaccharides, PMNCs as innovative, low-cost, and topical nanodrug formulations could offer promising potential to tackle most, if not all, of the conventional drug delivery issues in colorectal cancer therapy.