Selective and Controlled Release Responsive Nanoparticles with Adsorption-Pairing Synergy for Anthocyanin Extraction.

Anthocyanins with different structures have different anti-inflammatory and anti-cancer properties. Precise structural use can improve the chemopreventive effects of anthocyanins and enhance treatment outcomes because the anthocyanin structure influences its functional sites and activities. However, owing to the available variety of anthocyanins and their complex structures, the low matching of intermolecular forces between existing adsorbents and anthocyanins limits the targeted separation of anthocyanin monomers. Short-range and efficient selective binding, which is difficult to achieve, is the current focus in the extraction field. We here developed self-assembled Fe3O4-based nano adsorbers with different surface modifications based on adsorption-pairing synergy. The electrostatic force, coordination bond, hydrogen bond, and π-π* bond together induced selective adsorption between Fe3O4 nanoparticles and anthocyanin molecules. An acid-release solution disrupted the polarity balance in the aforementioned association system, thereby promoting the controlled release of anthocyanins. Among the candidates, the effects of morphology, particle size, surface charge, and functional group on adsorption performance were analyzed. The polyacrylamide-modified magnetic Fe3O4 nanoparticles were found to be favorable for selectively extracting anthocyanin, with an adsorption capacity of 19.74 ± 0.07 mg g-1. The release percentage of cyanidin-3-O-glucoside reached up to 98.6% ± 1.4%. This study offers a scientific basis for developing feasible nanotechniques to extract anthocyanins and plant active substances.

Chirality-Dependent Tumor Phototherapy Using Amino Acid-Engineered Chiral Phosphorene.

Phosphorene, also known as black phosphorus nanosheet (BPNS), has been investigated as a nanoagent for tumor therapy. However, promoting its intracellular accumulation while preventing the cytoplasmic decomposition remains challenging. Herein, for the first time, we propose a chiral BPNS designed through surface engineering based on amino acids with high biocompatibility and an abundant source for application in chirality-dependent tumor phototherapy based on its intracellular metabolism. The advantage of using cysteine (Cys) over other amino acids was that its d, l, or dl-form could efficiently work as the chirality inducer to modify the BPNS through electrostatic interaction and prevent alterations in the intrinsic properties of the BPNS. In particular, d-Cys-BPNS displayed an approximately threefold cytotoxic effect on tumor cells compared with l-Cys-BPNS, demonstrating a chirality-dependent therapy behavior. d-Cys-BPNS not only promoted high intracellular content but also showed resistance to cytoplasmic decomposition. Cys-engineered BPNS also demonstrated chirality-dependent phototherapy effects on tumor-bearing mice, in proximity to the results in vitro. Chiral engineering is expected to open new avenues that could promote the use of BPNS in tumor phototherapy and boost chiral nanomedicine.

3D magnetic nanocomposite scaffolds enhanced the osteogenic capacities of rat bone mesenchymal stem cells in vitro and in a rat calvarial bone defect model by promoting cell adhesion.

Magnetic scaffolds incorporated with iron oxide nanoparticles (IONPs) are biocompatible and present excellent osteogenic properties. However, the underlying mechanism is unclear. In this study, 3D-printed poly(lactic-co-glycolic acid) scaffolds were coated with IONPs using layer-by-layer assembly (Fe-scaffold) to prepare magnetic scaffolds. The effects of this modification on osteogenesis were investigated by comparison with untreated scaffolds (Uncoated-scaffold). The results showed that the proliferation of rat bone mesenchymal stem cells (rBMSCs) on the Fe-scaffold was enhanced compared with those on the Uncoated-scaffold (p < 0.05). The alkaline phosphatase activity and expression levels of osteogenic-related genes of cells on the Fe-scaffold were higher than those on the Uncoated-scaffold (p < 0.05). Fe-scaffold was found to promote the cell adhesion compared with Uncoated-scaffold, including increasing the adhered cell number, promoting cell spreading and upregulating the expression levels of adhesion-related genes integrin α1 and ß1 and their downstream signaling molecules FAK and ERK1/2 (p < 0.05). Moreover, the amount of new bone formed in rat calvarial defects at 8 weeks decreased in the order: Fe-scaffold > Uncoated-scaffold > Blank-control (samples whose defects were left empty) (p < 0.05). Therefore, 3D magnetic nanocomposite scaffolds enhanced the osteogenic capacities of rBMSCs in vitro and in a rat calvarial bone defect model by promoting cell adhesion. The mechanisms were attributed to the alteration in its hydrophilicity, surface roughness, and chemical composition.

Moderate cooling coprecipitation for extremely small iron oxide as a pH dependent T1-MRI contrast agent.

Iron based nanomedicine (IBNM) has been one powerful diagnostic tool as a magnetic resonance imaging (MRI) contrast agent (CA) in the clinic for years. Conventional IBNMs are generally employed as T2-MRI CAs, but most of them are constrained in clinical indication expansion by magnetic susceptibility artifacts. In comparison, extremely small iron oxide (ESIO) with a core size less than 5 nm has demonstrated the T1-MRI effect, which provides prospects for a Gd-based agent alternative. Nevertheless, currently developed ESIOs for T1-MRI CAs always require harsh conditions such as a high temperature and high boiling point reagent. Moreover, very few of the currently developed ESIOs meet the stringent pharmaceutical standard. Herein, on the basis of a crystal nuclear precipitation-dissolution equilibrium mechanism and outer/inner sphere T1-MRI theory, monodisperse ESIOs with an average size of 3.43 nm (polydispersity index of 0.104) are fabricated using a moderate cooling procedure with mild coprecipitation reaction conditions. The as-synthesized ESIOs display around 3-fold higher T1 MRI signal intensity than that of commercial Ferumoxytol (FMT), comparable to that of Gd-based CAs in vitro. Additionally, the T1-MRI performance of the ESIOs is pH dependent and delivers bright signal augmentation. Eventually, the internalization into mesenchymal stem cells of the ESIO is realized in the absence of a transferring agent. Considering the identical structure and composition of the ESIOs as compared to that of FMT, they could meet the pharmaceutical criteria, thus providing great potential as T1-MRI Cas, for instance as stem cell tracers.

Gold Nanoparticle Probe-Assisted Antigen-Counting Chip Using SEM.

Currently, it remains challenging to count protein-biomarker molecules present in a small droplet of biological samples. Herein, we propose a gold nanoparticle (GNP) probe-assisted sandwich-counting strategy that relies on a GNP probe, an antibody-functionalized chip to "count" antigen molecules using a scanning electron microscope. Both standard carcinoembryonic antigen (CEA) and two real CEA-related tumor samples (tumor tissues and serum) were assayed to demonstrate the proof-of-concept of the counting strategy. Results show that our method is excellently correlative with enzyme-linked immuno-sorbent assay (ELISA) that is widely used in clinics for antigen or antibody detection and the limit of detection of our enumeration strategy reaches down to 0.045 ng/mL, which is ∼40 times more sensitive than the conventional ELISA. Therefore, our GNP probe-assisted sandwich-counting strategy has the potential to be used for quantification of protein biomarkers at ultralow concentrations in early tumor specimens and detection of target proteins in much diluted concentrations.

Roles of PIP2 in the membrane binding of MIM I-BAR: insights from molecular dynamics simulations.

In order to probe the roles of PIP2 in the interactions between MIM I-BAR and model membranes, we performed a series of 10 µs-scale coarse-grained molecular dynamics simulations. Our results indicate that PIP2 plays predominant roles in the membrane binding of MIM I-BAR in a concentration-dependent manner and via electrostatic interactions. Besides, we find that the occurrence of the membrane curvature may induce the re-distribution of lipids in the membrane and result in the local enrichment of PIP2 at negatively curved membrane areas. Combining these roles of PIP2 in the membrane binding of MIM I-BAR helps explain how MIM I-BAR senses negative curvature and, thus, contributes to maintaining membrane protrusions.

Radiosensitivity enhancement of Fe3O4@Ag nanoparticles on human glioblastoma cells.

Radiotherapy is one of the main therapeutic methods for cancers, but radiation resistance of cancer cells still remains a serious concern. Searching for radiosensitizers to overcome such resistance is therefore urgently required. The goal of this study is to evaluate and compare the radiosensitizing efficacy of Fe3O4-OA, Ag and Fe3O4@Ag nanoparticles on U251 cells. The results show that Fe3O4@Ag nanoparticles have the highest ability of radiosensitization among the three nanoparticles. The underlying mechanism of Fe3O4@Ag nanoparticles' radiosensitivity enhancement is through decrease of the cytoprotective autophagy at the early stage, and increase of the calcium-dependent apoptosis at the later stage. These findings suggest the potential application of Fe3O4@Ag nanoparticles as a highly effective nano-radiosensitizer for the treatment of glioblastoma cells.

Optimizing purification process of MIM-I-BAR domain by introducing atomic force microscope and dynamics simulations.

MIM (missing in metastasis) is a member of I-BAR (inverse BAR) domain protein family, which functions as a putative metastasis suppressor. However, methods of gaining high purity MIM-I-BAR protein are barely reported. Here, by optimizing the purification process including changing the conditions of cell lysate and protein elution, we successfully purified MIM protein. The purity of the obtained protein was up to ∼90%. High-resolution atomic force microscope (AFM) provides more visual images, ensuring that we can observe the microenvironment around the target protein, as well as the conformations of the purification products following each purification process. MIM protein with two different sizes were observed on mica surface with AFM. Combining with molecular dynamics simulations, these molecules were revealed as MIM monomer and dimer. Furthermore, our study attaches importance to the usage of imidazole with suitable concentrations during the affinity chromatography process, as well as the removal of excessive imidazole after the affinity chromatography process. All these results indicate that the method described here was successful in purifying MIM protein and maintaining their natural properties, and is supposed to be used to purify other proteins with low solubility.

Development of serum iron as a biological dosimeter in mice.

Even though serum iron is a commonly used parameter in iron metabolism, it has not yet been applied for biological dosimetry purpose. A new biological dosimeter based on serum iron has been developed in this work. Serum iron levels in mice subjected to gamma rays from a (60)Co source were detected with the use of ferrous. The doses are from 0.2-7 Gy with a dose rate of 0.2 Gy/min. The results demonstrate that serum iron level increases with increasing dose. The detection limit based on serum iron has a lower limit of dose detection of about 0.5 Gy and the maximal increase of serum iron observed is maintained 4 h after γ irradiation. Therefore the best suggested time for blood collection is within 4 h after γ irradiation. Two dose-response relationships were observed with both according to degrees of the increase of serum iron levels and different intervals after γ irradiation. The first is a linear relationship of y = 0.98x + 6.76 (r = 0.98) obtained 10 min after γ irradiation; the second is the linear quadratic relationship of y = -0.07x(2) + 1.02x + 6.45 (r = 0.99) obtained 7 days after γ irradiation. The absorbed doses of mice estimated with the use of both these two dose-response relationships were close to the actual dose of 1 Gy. It is concluded that serum iron is a quick, simple and sensitive biomarker for early assessment of the absorbed dose of mice.

Gamma-radiation synthesis of nano/micrometer-scale single-crystalline large gold plates.

An original solution phase approach was developed for the synthesis of single-crystal Au nanoprims with anisotropic structure of triangular, hexagonal and truncated triangular, nanometre or micrometer scale, and nanometer thickness. It has been confirmed that the Fe3O4 magnetite nanoparticles and (3-aminopropyl) triethoxysilane (APTES) coated on the magnetite nanoparticles play important roles in the formation of Au nanoplates. Significantly, such Au nanoplates exhibit remarkable optical properties, both the dipole plasmon resonance and the quadrupole plasmon resonance were observed. And the selected area electron diffraction (SAED) pattern shows the nanoplates obtained were single crystals with (111) plans as two basal surfaces. The growth of gold nanoplates in the solution with time had been monitored by microscopic and spectroscopic techniques to allow the detection of several key intermediates in the growth process. To our knowledge, this is the first report on the production of large planar gold nanostructures with gamma irradiation in combination of another nanocomposite materials (APTES-Fe3O4).