In Vitro and in Vivo Studies of Folate-Functionalized PEGylated Chitosan/Superparamagnetic Iron Oxide Nanoparticle for the Fibrosarcoma-Targeted Delivery of Paclitaxel

Abstract

Abstract Fibrosarcoma is a rare type of cancer that affects cells known as fibroblasts that is malignant, locally recurring, spreading tumor in fibrous. In this work, an iron plate immersed in an aqueous solution of double-added deionized water, supplemented with potassium permanganate solution (KMnO4) was carried out by pulsed-laser removal method. Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized using different laser wavelengths (1064, 532, and 266 nm) at a fluence of 28 J/cm2 with 100 shots of the iron plate to control the concentration, shape, and size of the prepared high-stability SPIONs. The drug nanocarrier was synthesized by coating SPION with paclitaxel (PTX)-loaded chitosan (Cs) and polyethylene glycol (PEG). This nanosystem was functionalized by folate (FA) targeting receptors. The physiochemical characteristics of SPION@Cs-PTX-PEG-FA nanoparticles were evaluated and confirmed by infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, electron diffraction, atomic force microscopy, and dynamic light scattering methods. The cell internalization, cytotoxicity assay, apoptosis induction, and gene expression of SPION@Cs-PTX-PEG-FA in fibrosarcoma cell lines were estimated respectively. In vivo studies utilized BALB/c tumor-bearing mice. Results showed that SPION@Cs-PTX-PEG-FA exhibited suitable physical stability, spherical shape, desirable size, and charge. The SPION@Cs-PTX-PEG-FA inhibited the proliferation and induced the apoptosis of cancer cells (P < 0.01). In vivo study results showed that SPION@Cs -PTX-PEG-FA decreased the tumor size significantly compared with free PTX and control samples (P < 0.05), leading to longer survival, significantly enhanced splenocyte proliferation and IFN-γ level, and significantly diminished IL-4 level. All these findings indicated the potential of SPION@Cs-PTX-PEG-FA as an antitumor therapeutic agent.