Cuicui Ge

Synthesis of PEGylated Ferrocene Nanoconjugates as the Radiosensitizer of Cancer Cells

Radiation is one of the most widely used methods for cancer diagnosis and therapy. Herein, we report a new type of radiation sensitizer (Fc-PEG) by a facile one-step reaction of conjugating the hydrophilic PEG chain with hydrophobic ferrocene molecule. The chemical composition and structure of Fc-PEG have been thoroughly characterized by FT-IR, NMR, GPC, and MALDI-TOF mass spectrometry. This Fc-PEG conjugate could self-assemble in aqueous solution into spherical aggregates, and it was found that the exposure to 4 Gy of X-ray radiation have little influence on the shape and size of these aggregates. After the chemical bonding with PEG chains, the uptake level of Fe element could be enhanced via the formation of aggregates. The live/dead, CCK-8, as well as apoptosis assays, indicated that the death of cancer cells can be obviously increased by X-ray radiation after the incubation of these Fc-based nanoconjugates, which might be served as the radiation sensitizer toward cancer cells. We suggest that this radiosensitizing effect comes from the enhancement of reactive oxygen specimen (ROS) level as denoted by both flow cytometric and fluorescence microscopic analysis. The enhanced radiation sensitivity of cancer cells is contributed by the synergic effect of Fe-induced radiation-sensitizing and the increased uptake of nanoconjugates after polymeric grafting.

Facile synthesis of magnetic core–shell nanocomposites for MRI and CT bimodal imaging

With the development of nanotechnology, nanocomposites have been used as bimodal contrast agents for magnetic resonance (MR) and computed tomography (CT) imaging. We have developed a facile method for the synthesis of iron oxide@bismuth sulfide magnetic core-shell nanocomposites. These bifunctional nanocomposites can be made water-soluble via PEG coating and present strong MRI/CT contrast enhancement. Evaluation of cytotoxicity by MTT assay shows that the nanocomposites have low cytotoxicity. The results illustrate that the nanocomposites have great potential as bimodal imaging agents for MR/CT.

Enhanced Radiotherapy using Bismuth Sulfide Nanoagents Combined with Photo-thermal Treatment

Nanotechniques that can improve the effectiveness of radiotherapy (RT) by integrating it with multimodal imaging are highly desirable. Results In this study, we fabricated Bi2S3 nanorods that have attractive features such as their ability to function as contrast agents for X-ray computed tomography (CT) and photoacoustic (PA) imaging as well as good biocompatibility. Both in vitro and in vivo studies confirmed that the Bi2S3 nanoagents could potentiate the lethal effects of radiation via amplifying the local radiation dose and enhancing the anti-tumor efficacy of RT by augmenting the photo-thermal effect. Furthermore, the nanoagent-mediated hyperthermia could effectively increase the oxygen concentration in hypoxic regions thereby inhibiting the expression of hypoxia-inducible factor (HIF-1α). This, in turn, interfered with DNA repair via decreasing the expression of DNA repair-related proteins to overcome radio-resistance. Also, RT combined with nanoagent-mediated hyperthermia could substantially suppress tumor metastasis via down-regulating angiogenic factors. Conclusion In summary, we constructed a single-component powerful nanoagent for CT/PA imaging-guided tumor radiotherapy and, most importantly, explored the potential mechanisms of nanoagent-mediated photo-thermal treatment for enhancing the efficacy of RT in a synergistic manner.

Inhibition of the proteasome activity by graphene oxide contributes to its cytotoxicity

Abstract Due to its hydrophobicity and other unique physicochemical properties, graphene oxide (GO) has been extensively utilized in various biological applications. However, introducing nanomaterials into the biological environment may raise serious risk in terms of nanotoxicity, leading to some unintended changes to the structure and the function of other biomolecules. This study investigates the interaction of GO with the ubiquitin–proteasome system, one of the essential machineries in the cellular metabolism, using a combination of experimental and computational approaches. The experimental results show that GO could adsorb the 20S proteasome, causing a dose-dependent suppression of the proteolytic activity of proteasome. This adverse effect eventually disturbed other important cellular activities relevant to cell cycle and survival. Meanwhile, the molecular dynamics simulations revealed that when 20S proteasome was adsorbed onto the graphene surface, the central gate in the outer ring (α-subunit) for the entry and the exit of the peptide ligand to the protease active site was effectively blocked. These findings of GO induced functional disturbance of 20S proteasome provides a novel perspective to understand the molecular mechanism of GO’s cytotoxicity, which might further promote applications of GO in potential therapies for various cancers due to the abnormal elevation of the relevant proteasome activities.

Evaluation of the structure–activity relationship of carbon nanomaterials as antioxidants

AIMnTo develop the potential application of carbon nanomaterials as antioxidants calls for better understanding of how the specific structure affects their antioxidant activity.nnnMATERIALS & METHODSnSeveral typical carbon nanomaterials, including graphene quantum dots and fullerene derivatives were characterized and their radical scavenging activities were evaluated; in addition, the in vitro and in vivo radioprotection experiments were performed.nnnRESULTSnThese carbon nanomaterials can efficiently scavenge free radicals in a structure-dependent manner. In vitro assays demonstrate that administration of these carbon nanomaterials markedly increases the surviving fraction of cells exposed to ionizing radiation. Moreover, in vivo experiments confirm that their administration can also increase the survival rates of mice exposed to radiation.nnnCONCLUSIONnAll results confirm that large, buckyball-shaped fullerenes show the strongest antioxidant properties and the best radioprotective efficiency. Our work will be useful in guiding the design and optimization of nanomaterials for potential antioxidant and radioprotection bio-applications.