Abstract

The toxicity of superparamagnetic iron oxide nanoparticles (SPIONs) is still a vital topic of debate and the mechanisms remain unclear. In the present study, overdose SPIONs could induce osteosarcoma cell death and the effects were exaggerated when combined with spinning magnetic field (SMF). In the combination group, mitochondrial transmembrane potential decrease more obviously and reactive oxygen species (ROS) was found to generate much higher in line with that of the apoptosis ratio. Meantime, amount of autophagy was induced. Inhibiting the autophagy generation by 3-methyladenine (3-MA) increase cell viability but decrease the caspase 3/7 and caspase 8 activities in combination groups, and inhibiting apoptosis took the same effect. In the end, the SPIONs effects on xenograft mice was examed by intratumoral injection. The result showed that the combination group could greatly decrease the tumor volume and prolong the lifespan of mice. In sum, the result indicated that overdose SPIONs induced ROS generation, and excessive ROS induced by combination of SPIONs and SMF contribute to autophagy formation, which play a apoptosis-promoting role that formed as a platform to recruits initiate the caspase activities.

Highlights

  • Today, nanotechnology and engineered nanoparticles (NPs) are widely used in healthcare and life sciences fields, medical and biotechnological applications areas [1, 2]

  • The result indicated that overdose Superparamagnetic iron oxide nanoparticles (SPIONs) induced reactive oxygen species (ROS) generation, and excessive ROS induced by combination of SPIONs and spinning magnetic field (SMF) contribute to autophagy formation, which play a apoptosispromoting role that formed as a platform to recruits initiate the caspase activities

  • The size ranged from 12 nm to 21 nm showing a mode value of 18 nm (Figure 1B). magnetic measurement on SPIONs indicated that the particles are superparamagnetic at room temperature, as showed in Figure 1C, there was no coercive force in hysteresis loop of SPIONs, the magnetization of the particles approached the saturation values (67.9 emu/g) under a large external field, a little less than the bulk magnetite of 84 emu/g [21]

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Summary

Introduction

Nanotechnology and engineered nanoparticles (NPs) are widely used in healthcare and life sciences fields, medical and biotechnological applications areas [1, 2]. SPIONs exhibit magnetic behavior only there is a magnetic field, so they are of great interest for applications in vivo and in vitro [7, 8]. Ferroferric oxide (Fe3O4) nanoparticles, one example of the type of material, display great potential for medical applications. It is always emphasized that the SPIONs is low toxicity, some recent studies have showed that these NPs might induce cellular apoptosis or other responses [17]. The NPs can display cytotoxicity and apoptosis in nonsmall lung cancer cells but only induce limited toxicity to cervical cancer cells [17].Several mechanisms for SPIONsinduced cell and tissue injury are supported by limited experimental evidence. One hypothesis that are the most developed for nanoparticle toxicity is reactive oxygen species (ROS), which is believed to induce damage in protein, DNA and tissue [18]

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