Controlling the Transverse Proton Relaxivity of Magnetic Graphene Oxide

The engineering of materials with controlled magnetic properties by means other than a magnetic feld is of great interest in nanotechnology. In this study, we report engineered magnetic graphene oxide (MGO) in the nanocomposite form of iron oxide nanoparticles (IO)-graphene oxide (GO) with tunable core magnetism and magnetic resonance transverse relaxivity (r2). These tunable properties are obtained by varying the IO content on GO. The MGO series exhibits r2 values analogous to those observed in conventional single core and cluster forms of IO in diferent size regimes—motional averaging regime (MAR), static dephasing regime (SDR), and echo-limiting regime (ELR) or slow motion regime (SMR). The maximum r2 of 162±5.703mM−1s−1 is attained for MGO with 28 weight percent (wt%) content of IO on GO and hydrodynamic diameter of 414 nm, which is associated with the SDR.These fndings demonstrate the clear potential of magnetic graphene oxide for magnetic resonance imaging (MRI) applications

Photodynamic Therapeutic Effect of Nanostructured Metal Sulfide Photosensitizers for Cancer Treatment

Photodynamic therapy (PDT) utilizes photosensitizers (PSs) to produce reactive oxygen species (ROSs) upon irradiation, which causes the shutdown of vessels and deprives the tumor of nutrients and oxygen, and in turn induces adverse effects on the immune system. However, significant efforts are needed to increase the efficiency in PDT in terms of light delivery to specific PSs for the clinical treatment of tumors located deep under the skin. Even though PDT offers a disease site-specific treatment modality, current efforts are directed to improve the solubility (in body fluids and injectable solvents), photostability, amphiphilicity (for tissue penetration), elimination, and systemic toxicity of traditional PSs based on porphyrin derivatives. Nanostructured materials show promising features to achieve most of such combined efforts. They can be artificially engineered to carry multiple theranostic agents onto targeted tumor sites. However, recent studies on photosensitive Cd-based nanostructures, mostly used in PDT, indicate that leeching of Cd2+ ions is stimulated when they are exposed to harsh biological conditions for continuous periods of time, thus making them acutely toxic and hindering their applications in in vivo settings. Since nanostructured materials are not completely immune to degradation, great strides have been made to seek new alternatives. In this review, we focus on the latest advances of Cd-free nanostructured metal transition sulfides (MTSs) as alternative PSs and study their high-energy transfer efficiency, rational designs, and potential applications in cancer-targeted PDT. Nanostructured MTSs are discussed in the context of their versatility to serve as phototherapy agents and superior properties, including their strong absorption in the NIR region, excellent photothermal conversion efficiency, controlled reactive oxygen species (ROS) production, versatile surface chemistry, high fluorescence, and structural and thermal stability. We discuss the latest advancements in correlating the self-aggregation of MTSs with their passive tumor cell targeting, highlighting their ability to efficiently produce ROSs, and mitigating their dark toxicity through polymeric functionalization. Treatment of deep-seated tumors by using these PSs upon preferential uptake by tumor tissues (due to the enhanced permeability and retention effect) is also reviewed. We finally summarize the main future perspectives of MTSs as next-generation PSs within the context of cancer theranostics

Graphene Oxide/ZnS:Mn Nanocomposite Functionalized with Folic Acid as a Nontoxic and Effective Theranostic Platform for Breast Cancer Treatment

Nanoparticle-based cancer theranostic agents generally suffer of poor dispersability in biological media, re-agglomeration over time, and toxicity concerns. To address these challenges, we developed a nanocomposite consisting of chemically-reduced graphene oxide combined with manganese-doped zinc sulfide quantum dots and functionalized with folic acid (FA-rGO/ZnS:Mn). We studied the dispersion stability, Doxorubicin (DOX) loading and release efficiency, target specificity, internalization, and biocompatibility of FA-rGO/ZnS:Mn against folate-rich breast cancer cells, and compared to its uncoated counterpart (rGO/ZnS:Mn). The results indicate that DOX is adsorbed on the graphene surface via π–π stacking and hydrophobic interaction, with enhanced loading (~35%) and entrapment (~60%) efficiency that are associated to the chelation of DOX and surface Zn2+ ions. DOX release is favored under acidic conditions reaching a release of up to 95% after 70 h. Membrane integrity of the cells assessed by Lactate dehydrogenase (LDH) release indicate that the surface passivation caused by folic acid (FA) functionalization decreases the strong hydrophobic interaction between the cell membrane wall and the edges/corners of graphene flakes. Chemotherapeutic effect assays reveal that the cancer cell viability was reduced up to ~50% at 3 µg/mL of DOX-FA-rGO/ZnS:Mn exposure, which is more pronounced than those obtained for free DOX at the same doses. Moreover, DOX-rGO/ZnS:Mn did not show any signs of toxicity. An opposite trend was observed for cells that do not overexpress the folate receptors, indicating that FA functionalization endows rGO/ZnS:Mn with an effective ability to discriminate positive folate receptor cancerous cells, enhancing its drug loading/release efficiency as a compact drug delivery system (DDS). This study paves the way for the potential use of functionalized rGO/ZnS:Mn nanocomposite as a platform for targeted cancer treatment

Analysis of lipid adsorption on nanoparticles by nanoflow liquid chromatography-tandem mass spectrometry

Nanoparticles (NPs) tend to adsorb matrix molecules like proteins and lipids incubated with biological fluids, forming a biological corona. While the formation and functions of protein corona have been studied extensively, little attention has been paid to lipid adsorption on NPs. However, lipids are also abundantly present in biological fluids and play important roles in processes like cell signaling and angiogenesis. Therefore, in this study, we established the analytical procedure for study of lipid adsorption on three different types of NPs in two matrices: human serum and heavy cream, using nanoflow liquid chromatography-mass spectrometry (nanoflowLC-MS). Serum was chosen to represent the common environment the NPs would be present once entering human body, and heavy cream was the representative food matrix NPs may be added to improve the color or taste. Steps of liquid-liquid extraction were established and optimized to achieve maximum recovery of the adsorbed, standard lipids from the NPs. Then, the LC-MS/MS method was developed to attain base-line separation of the standard lipids that represent the major lipid classes. At last, the lipid adsorption profiles of the three NPs were compared. We found that the lipid adsorption profile on the same type of NP was significantly different between the two matrices. The established method will help us investigate lipid adsorption on additional NPs and reveal how it could be affected by the physiochemical properties of NPs and the presence of proteins and other components in the biological matrix

Additional file 1: Figure S1. of Enhanced MRI T 2 Relaxivity in Contrast-Probed Anchor-Free PEGylated Iron Oxide Nanoparticles

XRD patterns of bare Fe3O4 nanoparticles (SPION), PEGylated Fe3O4 nanoparticles (PEG-SPION) and pure PEG powder. Figure S2. (a-e) Bright field HRTEM images of PEG-SPION showing Fe3O4 cores fully coated with PEG. Figure S3. Zeta potential measurements showing the isoelectric point (IEP) of SPION and SPION stabilized with PEG (3350). Figure S4. DLS measurements of SPION and PEG-SPION dispersed in deionized water. Figure S5. A proposed mechanism of dipole cationic binding of ether group of PEG to Fe3O4 surface and hydration process of PEG for aqueous dispersibility. (DOCX 71194 kb

Safer-by-design flame-sprayed silicon dioxide nanoparticles: the role of silanol content on ROS generation, surface activity and cytotoxicity

Background Amorphous silica nanoparticles (SiO2 NPs) have been regarded as relatively benign nanomaterials, however, this widely held opinion has been questioned in recent years by several reports on in vitro and in vivo toxicity. Surface chemistry, more specifically the surface silanol content, has been identified as an important toxicity modulator for SiO2 NPs. Here, quantitative relationships between the silanol content on SiO2 NPs, free radical generation and toxicity have been identified, with the purpose of synthesizing safer-by-design fumed silica nanoparticles. Results Consistent and statistically significant trends were seen between the total silanol content, cell membrane damage, and cell viability, but not with intracellular reactive oxygen species (ROS), in the macrophages RAW264.7. SiO2 NPs with lower total silanol content exhibited larger adverse cellular effects. The SAEC epithelial cell line did not show any sign of toxicity by any of the nanoparticles. Free radical generation and surface reactivity of these nanoparticles were also influenced by the temperature of combustion and total silanol content. Conclusion Surface silanol content plays an important role in cellular toxicity and surface reactivity, although it might not be the sole factor influencing fumed silica NP toxicity. It was demonstrated that synthesis conditions for SiO2 NPs influence the type and quantity of free radicals, oxidative stress, nanoparticle interaction with the biological milieu they come in contact with, and determine the specific mechanisms of toxicity. We demonstrate here that it is possible to produce much less toxic fumed silicas by modulating the synthesis conditions.ISSN:1743-897

Controlling the transverse proton relaxivity of magnetic graphene oxide

Abstract The engineering of materials with controlled magnetic properties by means other than a magnetic field is of great interest in nanotechnology. In this study, we report engineered magnetic graphene oxide (MGO) in the nanocomposite form of iron oxide nanoparticles (IO)-graphene oxide (GO) with tunable core magnetism and magnetic resonance transverse relaxivity (r2). These tunable properties are obtained by varying the IO content on GO. The MGO series exhibits r2 values analogous to those observed in conventional single core and cluster forms of IO in different size regimes—motional averaging regime (MAR), static dephasing regime (SDR), and echo-limiting regime (ELR) or slow motion regime (SMR). The maximum r2 of 162 ± 5.703 mM−1s−1 is attained for MGO with 28 weight percent (wt%) content of IO on GO and hydrodynamic diameter of 414 nm, which is associated with the SDR. These findings demonstrate the clear potential of magnetic graphene oxide for magnetic resonance imaging (MRI) applications

T₁- and T₂‑weighted Magnetic Resonance Dual Contrast by Single Core Truncated Cubic Iron Oxide Nanoparticles with Abrupt Cellular Internalization and Immune Evasion

Conventional T₁- or T₂-weighted single mode contrast-enhanced magnetic resonance imaging (MRI) may produce false results. Thereby, there is a need to develop dual contrast agents, T₁- and T₂-weighted, for more accurate MRI imaging. The dual contrast agents should possess high magnetic resonance (MR) relaxivities, targeted tumor linking, and minimum recognition by the immune system. We have developed nitrodopamine-PEG grafted single core truncated cubic iron oxide nanoparticles (ND-PEG-tNCIOs) capable of producing marked dual contrasts in MRI with enhanced longitudinal and transverse relaxivities of 32 ± 1.29 and 791 ± 38.39 mM^–1 s^–1, respectively. Furthermore, the ND-PEG-tNCIOs show excellent colloidal stability in physiological buffers and higher cellular internalization in cancerous cells than in phagocytic cells, indicating the immune evasive capability of the nanoparticles. These findings indicate that tNCIOs are strong candidates for dual contrast MRI imaging, which is vital for noninvasive real-time detection of nascent cancer cells in vivo and for monitoring stem cells transplants