Cisplatin-loaded Superparamagnetic Nanoparticles Modified with PCL-PEG Copolymers and Their Effectiveness Evaluation on Lymphoma Cell Line

Cancer is one of the causes of morbidity and mortality in developed and under-developed countries. Different strategies are under evaluation for cancer therapy including chemotherapy, radiotherapy, and surgery. However, the treatment can be affected because of the lack of the desired effect and severe side effects. For these reasons, discovering an improved cancer therapy strategy has been one of the most important research efforts worldwide. Cisplatin is considered one of the most effective used chemotherapy agents in the treatment of a variety of tumors. However, its use is limited because of its toxicity to normal cells. In addition, non-specificity and high dosage of drugs are the other important reasons which practically limit their application. Drug delivery systems can overcome these challenges by enhancing the therapeutic efficacy and reducing the adverse effects of anticancer agents. The application of nanoparticles as drug carriers has been widely studied for more than a decade (3). Magnetic nanoparticles are popular candidates in therapeutic systems and diagnostic applications that approved for clinical use by the Food and Medicine Administration (FDA) (5). In this study, we prepared superparamagnetic iron oxide nanoparticles Fe3O4 (SPIONs) that were modified through triblock poly (ethylene glycol)-poly (e-caprolactone)-poly (ethylene glycol) nanoparticles. These modified nanoparticles have been utilized for Cisplatin delivery on the lymphoma cell line (U937).

Magnetic nanoparticles were prepared by a co-precipitation method in the presence of Fe2+ and Fe3+ (9). In order to synthesize the polymer, ε-caprolactone and polyethylene glycol were polymerized by a ring-opening polymerization method. Triblock copolymer PCL-PEG-PCL was prepared through the ring-opening polymerization method (10). Magnetic iron nanoparticles were also prepared and confirmed using Fourier Transform Infrared Spectroscopy (FTIR) and X-ray diffraction spectrum (XRD). Superparamagnetic nanoparticles modified with PCL-PEG-PCL copolymers loaded with cisplatin were developed using the double emulsion solvent evaporation method (11). The encapsulation efficiency of cisplatin loaded in nanoparticles was evaluated through UV spectroscopy at 280 nm (12). Synthesized nanoparticles were evaluated in terms of particle size and morphology by dynamic light scattering (DLS) analysis and Scanning Electron Microscope (SEM), respectively. In addition, the chemical structure of PCL-PEG-PCL triblock copolymer and superparamagnetic nanoparticles modified with PCL-PEG-PCL copolymers loaded with cisplatin was confirmed using FTIR and proton nuclear magnetic resonance (1H-NMR). Finally, the effect of synthesized nanoparticles on the lymphoma cell line (U937) was investigated using MTT assay (13).

Magnetic iron nanoparticles were confirmed using FTIR and XRD. The size and shape of the nanoparticles were evaluated using DLS and SEM. The results show that the particle size was around 100-130 nm and the synthesized nanoparticles had uniform dispersion without aggregation. High entrapment of cisplatin was achieved using the double emulsion solvent evaporation method (98/07%). The hysteresis curves of iron magnetic nanoparticles and cisplatin-encapsulated magnetic nanoparticles PCL-PEG-PCL exhibited that in the presence of a magnetic field with an intensity up to 8000 Gauss, these particles have shown the magnetic properties (about 70 emu/g). When the magnetic field was removed, these nanoparticles lost their magnetic properties (0 emu/g). So, in the presence of a magnetic field, a magnetic orientation was demonstrated. The results of the cell viability assay using MTT dye showed that IC50 of free Cisplatin and Cisplatin-encapsulated magnetic nanoparticles PCL-PEG-PCL on the U937 cancerous cell line is 119.70 ± 4.46 µg/ml, 17.35 ± 1.48 µg/ml, 13.58 ± 1.59 µg/ml and 29.67 ± 1.99 µg/ml, 11.24 ± 0.82µg/ml, 7.10 ± 1.37µg/ml respectively for 24, 48 and 72 hours incubation time.  The anti-proliferative effect of cisplatin encapsulated in magnetic nanoparticles was more significantly cytotoxic on the cancerous target cells than free cisplatin.

Over the last decade, scientists have tried to develop new strategies for enhancing the therapeutic index while reducing side effects. In this regard, nanotechnology is considered one of the most effective strategies to which a huge share of research in this area is dedicated (3). Among all the nanoparticles SPIONs have attracted significant attention in cancer therapy because of their unique properties such as biocompatibility, biodegradability, and ease of chemical modification (5). The results of the study demonstrated that superparamagnetic nanoparticles modified with PCL-PEG copolymers efficiently delivered cisplatin into the U937 cells and demonstrated potent in-vitro anticancer activity which had a significant cytotoxic effect against lymphoma cell line (U937). Therefore, this delivery system can potentially be applied for the delivery of anti-cancer drugs and holds a great promise as an effective strategy for cancer treatment.