Development of a hypoxic nanocomposite containing high-Z element as 5-fluorouracil carrier activated self-amplified chemoradiotherapy co-enhancement.

The synergetic effect of chemoradiotherapy achievement is encouraging but significantly hampered by the prevalence of hypoxia, leading to drug/radiation resistance in solid tumours. To address the problem and improve the efficiency of cancer therapy, a lamellar-structure multifunctional graphene oxide (GO) drug-delivery system with an average size of 243 nm, co-delivering of metronidazole (MI), 5-fluorouracil (5-FU) and FePt magnetic nanoparticles (MNPs), was successfully designed and synthesized in the study. The integration of hypoxic drug carrier loading radiosensitizers and chemotherapeutic drugs simultaneously, combines the properties of hypoxia-sensitivity and chemoradiotherapy co-enhancement within a single nanoplatform, which is expected to provide new ideas for cancer treatment. Through in vitro tests, the hypoxia-sensitivity and cytotoxicity of intracellular reactive oxygen species (ROS) of the nanocomposites (NCs) were proved. Moreover, the additive effect between MI, 5-FU and FePt MNPs in cytotoxicity and radiation sensitization aspects is disclosed. It performs an enhanced cell proliferation inhibition and makes up a self-amplified radiotherapy enhancement system that improves radiation efficiency and cell radiosensitivity simultaneously. In conclusion, the study recommended a novel and promising multifunctional nanoplatform which performed a self-amplified effect that activated chemoradiotherapy co-enhancement.

FePt/GO Nanosheets Suppress Proliferation, Enhance Radiosensitization and Induce Autophagy of Human Non-Small Cell Lung Cancer Cells.

With the advancement of nanotechnology, various nanocomposites have been applied in the diagnostics and treatment of cancer. We synthetized FePt nanoparticles which were assembled on the surface of graphene oxide (GO). These novel FePt/GO nanosheets simultaneously act as a chemotherapy drug and enhance radiosensitivity. In this study, transmission electron microscope, dynamic light scattering, X-ray photoelectron spectroscope and Fourier transform infrared spectroscopy were used to characterize surface morphology and chemical composition of FePt/GO nanosheets (NSs). Their cytotoxicity in various cancer and normal cells was evaluated by cell counting kit-8 assay, and their effects on radiosensitization were determined by colony formation assay. To explore the underlying mechanisms, we measured the intracellular reactive oxygen species levels and autophagy formation. Monodansylcadaverine-staining, Western Blotting and ultrastructure analysis were utilized to assess autophagy. The results demonstrated that FePt/GO NSs not only selectively suppressed the proliferation of cancer cells, but also increased their radiosensitization. Moreover, FePt/GO NSs induced autophagy, which might result in promoted sensibilization of radiotherapy. In conclusion, with good safety and efficacy, FePt/GO NSs are safe and effective to suppress proliferation, enhance radiosensitization and induce autophagy of human non-small cell lung cancer cells. They are potential for the treatment of lung cancer.

FePt-Cys nanoparticles induce ROS-dependent cell toxicity, and enhance chemo-radiation sensitivity of NSCLC cells in vivo and in vitro.

FePt-Cys nanoparticles (FePt-Cys NPs) have been well used in many fields, despite their poor solubility and stability. We synthetized a cysteine surface modified FePt NPs, which exhibited good solubility, stability and biocompatibility. We explored the insight mechanisms of the antitumor effects of this new nanoparticle system in lung cancer cells. In the in vitro study, FePt-Cys NPs induced a reactive oxygen species (ROS) burst, which suppressed the antioxidant protein expression and induced cell apoptosis. Furthermore, FePt-Cys NPs prevented the migration and invasion of H1975 and A549 cells. These changes were correlated with a dramatic decrease in MMP-2/9 expression and enhanced the cellular attachment. We demonstrated that FePt-Cys NPs promoted the effects of chemo-radiation through activation of the caspase system and impairment of DNA damage repair. In the in vivo study, no severe allergies or drug-related deaths were observed and FePt-Cys NPs showed a synergistic effect with cisplatin and radiation. In conclusion, with good safety and efficacy, FePt-Cys NPs could therefore be potential sensitizers for chemoradiotherapy.