Abstract
Background: Despite the development of conventional therapies including surgery, radiotherapy, chemotherapy and hyperthermia, the prognosis remains very poor. Recently, integration of conventional therapy and multifunctional nanoparticles have attracted a lot of attention because it produces a synergistic effect and better diagnostic and therapeutic efficiency.
Objective: This study aimed to investigate the uptake and cytotoxic effects of Polycaprolactone (PCL)/chitosan (CHI)-coated Superparamagnetic Iron Oxide Nano-Graphene Oxide (SPION-NGO) as a carrier of 5-fluorouracil (5-Fu) and Radiofrequency (RF) hyperthermia using an Alternate Magnetic Field (AMF) with 13.56 MHz frequency on the proliferation capacity level of CT26 colon cancer cell line in a monolayer culture.
Method: The release of the newly synthesised 5-Fu-loaded PCL/CHI-SPION-NGO was measured in Phosphate Buffered Saline (PBS) using the dialysis bag method. The cellular uptake of 5-Fu-loaded PCL/CHI-SPIONNGO was measured using Atomic Absorption Spectroscopy (AAS). The cytotoxic effects of 5-Fu, 5-Fu- PCL/CHI-SPION-NGO and PCL/CHI-SPION-NGO with and without RF hyperthermia were determined using the colony formation assay.
Results: Particle size and zeta potential of 5-Fu-PCL/CHI-SPION-NGO and PCL/CHI-SPION-NGO were 61.2 nm and -1.87 mV and 43.4 nm and -10.19 mV, respectively. Spectroscopy results demonstrated that the cellular uptake of 5-Fu-PCL/CHI-SPION-NGO increased with elevated nanostructure concentrations. The results revealed that the proliferation capacity of the cells decreased with 5-Fu or 5-Fu-PCL/CHI-SPION-NGO in combination with RF hyperthermia. Furthermore, extent of reduction in colony number following treatment with 5-Fu-PCL/CHI-SPION-NGO in combination with AMF was significantly more than 5-Fu + hyperthermia.
Conclusion: Therefore, PCL/CHI-SPION-NGO can deliver 5-Fu more efficiently into the CT26 cells.
Keywords: 5-Fluorouracil, nano-graphene oxide, magnetic nanoparticles, alternative magnetic field, hyperthermia, colon cancer.
Graphical Abstract
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