Abstract
Background: The high incidence and mortality rates of cervical cancer pose a serious threat to women's health. Traditional chemotherapy has inevitable drawbacks of nonspecific tumor targeting, high toxicity, and poor therapeutic efficiency. In order to overcome these shortcomings, a novel multifunctional magnetic nanoparticles drug delivery system with tumor targeting and magnetic resonance imaging was developed to achieve precise diagnosis and targeted tumor killing effects.Methods: Transmission electron microscopy, dynamic light scatting and ultraviolet methods were used to characterize the nanoparticles in vitro. Cell function tests were performed by scratch, transwell and flow cytometry assays. MTT was used to detect the toxicity of the nanoparticles. The motion trajectory, drug release and uptake studies were carried out in vitro. The in vivo pharmacokinetic and drug distribution studies were verified by high performance liquid chromatography methods. Attenuation of the MRI signal by the nanoparticles and their enhanced antitumor efficiency were examined in vivo in mouse cervical cancer models. Sequencing and proteomics were used to detect the key antitumor molecules of the nanoparticles.Results: Multifunctional magnetic nanoparticles coated with ferric oxide nanoparticles and doxorubicin hydrochloride (DOX-Fe3O4-PEG-PLA-NPs) was prepared successfully. No toxicity was detected of PEG-PLA-NP, however, the tumor killing effect was enhanced under the alternating magnetic field significantly. The drug-release study showed that the cumulative release rates of NP groups were much less than free DOX group, while the drug release rate increased under acidic condition. In addition, DOX-Fe3O4-PEG-PLA-NPs showed improved internalized into carcinoma cells under magnetic field significantly. In vivo studies demonstrated that the combined therapy under an alternating magnetic field displayed improved therapeutic effect when compared with individual therapies as documented by the delayed tumor growth, inhibition of metastasis, and prolonged survival. The in vitro and in vivo MRI results showed that the multifunctional magnetic nanomaterial had a better MRI signal reduction effect and a higher T2 relaxation rate.Conclusions: We developed an cervical cancer targeting nano-carrier drug delivery system successfully, which showed perfect excellent T2 contrast magnetic resonance imaging, chemotherapy-sensitizing, tumor targeting , and anti-tumor effect, thus have the potential to be a new theranostic strategy for ovarian cancer patients.
Eccentric magnetic microcapsules for MRI-guided local administration and pH-regulated drug release