Use of an in silico knowledge discovery approach to determine mechanistic studies of silver nanoparticles-induced toxicity from in vitro to in vivo.

BACKGROUND: Silver nanoparticles (AgNPs) are considered a double-edged sword that demonstrates beneficial and harmful effects depending on their dimensions and surface coating types. However, mechanistic understanding of the size- and coating-dependent effects of AgNPs in vitro and in vivo remains elusive. We adopted an in silico decision tree-based knowledge-discovery-in-databases process to prioritize the factors affecting the toxic potential of AgNPs, which included exposure dose, cell type and AgNP type (i.e., size and surface coating), and exposure time. This approach also contributed to effective knowledge integration between cell-based phenomenological observations and in vitro/in vivo mechanistic explorations. RESULTS: The consolidated cell viability assessment results were used to create a tree model for generalizing cytotoxic behavior of the four AgNP types: SCS, LCS, SAS, and LAS. The model ranked the toxicity-related parameters in the following order of importance: exposure dose > cell type > particle size > exposure time ≥ surface coating. Mechanistically, larger AgNPs appeared to provoke greater levels of autophagy in vitro, which occurred during the earlier phase of both subcytotoxic and cytotoxic exposures. Furthermore, apoptosis rather than necrosis majorly accounted for compromised cell survival over the above dosage range. Intriguingly, exposure to non-cytotoxic doses of AgNPs induced G2/M cell cycle arrest and senescence instead. At the organismal level, SCS following a single intraperitoneal injection was found more toxic to BALB/c mice as compared to SAS. Both particles could be deposited in various target organs (e.g., spleen, liver, and kidneys). Morphological observation, along with serum biochemical and histological analyses, indicated that AgNPs could produce pancreatic toxicity, apart from leading to hepatic inflammation. CONCLUSIONS: Our integrated in vitro, in silico, and in vivo study revealed that AgNPs exerted toxicity in dose-, cell/organ type- and particle type-dependent manners. More importantly, a single injection of lethal-dose AgNPs (i.e., SCS and SAS) could incur severe damage to pancreas and raise blood glucose levels at the early phase of exposure.

Comparing different surface modifications of zinc oxide nanoparticles in the developmental toxicity of zebrafish embryos and larvae.

Nanotechnology allows for a greater quality of life, but may also cause environmental and organismic harm. Zinc oxide nanoparticles (ZnONPs) are one of the most commonly used metal oxide nanoparticles for commercial and industrial products. Due to its extensive use in various fields, there has already been much concern raised about the environmental health risks of ZnONPs. Many studies have investigated the toxicological profile of ZnONPs in zebrafish embryonic development; however, the specific characteristics of ZnONPs in zebrafish embryonic/larval developmental damage and their molecular toxic mechanisms of liver development are yet to be fully elucidated. This study aimed to reveal the hazard ranking of different surface modifications of ZnONPs on developing zebrafish and the toxicological mechanisms of these modified ZnONPs in liver tissue. The ~30 nm ZnONPs with amino- (NH2- ZnONPs) or carboxyl- (COOH-ZnONPs) modification were incorporated during the embryonic/larval stage of zebrafish. Severe toxicity was observed in both ZnONP groups, especially NH2-ZnONPs, which presented a higher toxicity in the low concentration groups. After prolonging the exposure time, the long-term toxicity assay showed a greater retardation in body length of zebrafish in the NH2-ZnONP group. Response data from multiple toxicity studies was integrated for the calculation of the EC50 values of bulk ZnO and ZnONPs, and the hazard levels were found to be decreasing in the order of NH2-, COOH-ZnONPs and bulk ZnO. Notably, NH2-ZnONPs induced ROS burden in the developing liver tissue, which activated autophagy-related gene and protein expression and finally induced liver cell apoptosis to reduce liver size. In conclusion, our findings are conducive to understanding the hazard risks of different surface modifications of ZnONPs in aquatic environments and will also be helpful for choosing the type of ZnONPs in future industrial applications.

The Effect of the Chorion on Size-Dependent Acute Toxicity and Underlying Mechanisms of Amine-Modified Silver Nanoparticles in Zebrafish Embryos.

As the worldwide application of nanomaterials in commercial products increases every year, various nanoparticles from industry might present possible risks to aquatic systems and human health. Presently, there are many unknowns about the toxic effects of nanomaterials, especially because the unique physicochemical properties of nanomaterials affect functional and toxic reactions. In our research, we sought to identify the targets and mechanisms for the deleterious effects of two different sizes (~10 and ~50 nm) of amine-modified silver nanoparticles (AgNPs) in a zebrafish embryo model. Fluorescently labeled AgNPs were taken up into embryos via the chorion. The larger-sized AgNPs (LAS) were distributed throughout developing zebrafish tissues to a greater extent than small-sized AgNPs (SAS), which led to an enlarged chorion pore size. Time-course survivorship revealed dose- and particle size-responsive effects, and consequently triggered abnormal phenotypes. LAS exposure led to lysosomal activity changes and higher number of apoptotic cells distributed among the developmental organs of the zebrafish embryo. Overall, AgNPs of ~50 nm in diameter exhibited different behavior from the ~10-nm-diameter AgNPs. The specific toxic effects caused by these differences in nanoscale particle size may result from the different mechanisms, which remain to be further investigated in a follow-up study.

The role of hypoxia-inducible factor-1α in zinc oxide nanoparticle-induced nephrotoxicity in vitro and in vivo.

BACKGROUND: Zinc oxide nanoparticles (ZnO NPs) are used in an increasing number of products, including rubber manufacture, cosmetics, pigments, food additives, medicine, chemical fibers and electronics. However, the molecular mechanisms underlying ZnO NP nephrotoxicity remain unclear. In this study, we evaluated the potential toxicity of ZnO NPs in kidney cells in vitro and in vivo. RESULTS: We found that ZnO NPs were apparently engulfed by the HEK-293 human embryonic kidney cells and then induced reactive oxygen species (ROS) generation. Furthermore, exposure to ZnO NPs led to a reduction in cell viability and induction of apoptosis and autophagy. Interestingly, the ROS-induced hypoxia-inducible factor-1α (HIF-1α) signaling pathway was significantly increased following ZnO NPs exposure. Additionally, connective tissue growth factor (CTGF) and plasminogen activator inhibitor-1 (PAI-1), which are directly regulated by HIF-1 and are involved in the pathogenesis of kidney diseases, displayed significantly increased levels following ZnO NPs exposure in HEK-293 cells. HIF-1α knockdown resulted in significantly decreased levels of autophagy and increased cytotoxicity. Therefore, our results suggest that HIF-1α may have a protective role in adaptation to the toxicity of ZnO NPs in kidney cells. In an animal study, fluorescent ZnO NPs were clearly observed in the liver, lungs, kidneys, spleen and heart. ZnO NPs caused histopathological lesions in the kidney and increase in serum creatinine and blood urea nitrogen (BUN) which indicate possible renal possible damage. Moreover, ZnO NPs enhanced the HIF-1α signaling pathway, apoptosis and autophagy in mouse kidney tissues. CONCLUSIONS: ZnO NPs may cause nephrotoxicity, and the results demonstrate the importance of considering the toxicological hazards of ZnO NP production and application, especially for medicinal use.

Rapid visualization of latent fingermarks using gold seed-mediated enhancement.

BACKGROUND: Fingermarks are one of the most important and useful forms of physical evidence in forensic investigations. However, latent fingermarks are not directly visible, but can be visualized due to the presence of other residues (such as inorganic salts, proteins, polypeptides, enzymes and human metabolites) which can be detected or recognized through various strategies. Convenient and rapid techniques are still needed to provide obvious contrast between the background and the fingermark ridges and to then visualize latent fingermark with a high degree of selectivity and sensitivity. RESULTS: In this work, lysozyme-binding aptamer-conjugated Au nanoparticles (NPs) are used to recognize and target lysozyme in the fingermark ridges, and Au+-complex solution is used as a growth agent to reduce Au+ from Au+ to Au0 on the surface of the Au NPs. Distinct fingermark patterns were visualized on a range of professional forensic within 3 min; the resulting images could be observed by the naked eye without background interference. The entire processes from fingermark collection to visualization only entails two steps and can be completed in less than 10 min. The proposed method provides cost and time savings over current fingermark visualization methods. CONCLUSIONS: We report a simple, inexpensive, and fast method for the rapid visualization of latent fingermarks on the non-porous substrates using Au seed-mediated enhancement. Au seed-mediated enhancement is used to achieve the rapid visualization of latent fingermarks on non-porous substrates by the naked eye without the use of expensive or sophisticated instruments. The proposed approach offers faster detection and visualization of latent fingermarks than existing methods. The proposed method is expected to increase detection efficiency for latent fingermarks and reduce time requirements and costs for forensic investigations.

1H Spin-Lattice Relaxation Processes in Solutions of H2N-Fe3O4 Nanoparticles: Insights from NMR Relaxometry.

1H spin-lattice relaxation experiments have been performed for water and glycerol/water solutions of H2N-Fe3O4 superparamagnetic nanoparticles (NPs) of about 7 nm diameter. The experiments encompass a broad frequency range covering 3 orders of magnitude, from 10 kHz to 10 MHz (referring to 1H resonance frequency), and have been performed in the temperature range from 298 to 313 K, varying the concentration of the superparamagnetic species. This extensive dataset has been used for twofold purposes. The first one is to serve as a challenge for thorough tests of theoretical models describing nuclear relaxation in solutions of superparamagnetic NPs, depending on their magnetic properties and dynamics of the solvent molecules. The challenge is posed by the wish to reproduce the data in a broad range of magnetic fields (not only at high fields) and by the need to explain the differences in the relaxation scenarios for water and glycerol/water solutions by varying only the solvent parameters. The second purpose is to get insights into the magnetic properties (electronic relaxation properties) of the nanoparticles due to their high applicational potential.

Formation of Ag nanoframes with facilitation of dithiols.

Two-dimensional Ag nanoprisms readily formed Ag triangular nanoframes upon electron beam irradiation. Following meso-2, 3-dimercaptosuccinicacid (DMSA) ripening behavior, continuous electron beam exposure transformed a solid nanoplate into a core/void/shell morphology, which then evolved into a hollow nanoframe structure. TEM was used to observe the ripening and etching processes of Ag nanoprisms as a function of DMSA concentration and electron irradiation time. X-ray diffraction (XRD) and FT-IR analysis were conducted to characterize the Ag nanoprism structure and surface before and after treatment with DMSA. X-ray photoelectron spectroscopy (XPS) was used to determine surface chemical compositions and indicated DMSA was adsorbed on the Ag nanoprisms in the form of Ag(+)-S(-). Raman measurements provided evidence of a disulfide group on Ag nanoprisms. Similar organosulfur structures such as mercaptosuccinic acid and 2-mercaptoacetic acid were also studied with results suggesting that the two S-H groups of dithiol DMSA played the crucial role in nanoframe fabrication. Using the same strategy with DMSA, the nano-architecture can be extended to 2D nanodiscs yielding nanorings.

Development of a cancer cells self­activating and miR­125a­5p expressing poly­pharmacological nanodrug for cancer treatment.

Cancer cells can acquire resistance to targeted therapeutic agents when the designated targets or their downstream signaling molecules develop protein conformational or activity changes. There is an increasing interest in developing poly­pharmacologic anticancer agents to target multiple oncoproteins or signaling pathways in cancer cells. The microRNA 125a­5p (miR­125a­5p) is a tumor suppressor, and its expression has frequently been downregulated in tumors. By contrast, the anti­apoptotic molecule BIRC5/SURVIVIN is highly expressed in tumors but not in the differentiated normal tissues. In the present study, the development of a BIRC5 gene promoter­driven, miR­125a­5p expressing, poly­L­lysine­conjugated magnetite iron poly­pharmacologic nanodrug (pL­MNP­pSur­125a) was reported. The cancer cells self­activating property and the anticancer effects of this nanodrug were examined in both the multidrug efflux protein ABCB1/MDR1­expressing/­non­expressing cancer cells in vitro and in vivo. It was demonstrated that pL­MNP­pSur­125a decreased the expression of ERBB2/HER2, HDAC5, BIRC5, and SP1, which are hot therapeutic targets for cancer in vitro. Notably, pL­MNP­pSur­125a also downregulated the expression of TDO2 in the human KB cervical carcinoma cells. PL­MNP­pSur­125a decreased the viability of various BIRC5­expressing cancer cells, regardless of the tissue origin or the expression of ABCB1, but not of the human BIRC5­non­expressing HMEC­1 endothelial cells. In vivo, pL­MNP­pSur­125a exhibited potent antitumor growth effects, but without inducing liver toxicity, in various zebrafish human­ABCB1­expressing and ABCB1­non­expressing tumor xenograft models. In conclusion, pL­MNP­pSur­125a is an easy­to­prepare and a promising poly­pharmacological anticancer nanodrug that has the potential to manage numerous malignancies, particularly for patients with BIRC5/ABCB1­related drug resistance after prolonged chemotherapeutic treatments.

Toxic Effects and Mechanisms of Silver and Zinc Oxide Nanoparticles on Zebrafish Embryos in Aquatic Ecosystems.

The global application of engineered nanomaterials and nanoparticles (ENPs) in commercial products, industry, and medical fields has raised some concerns about their safety. These nanoparticles may gain access into rivers and marine environments through industrial or household wastewater discharge and thereby affect the ecosystem. In this study, we investigated the effects of silver nanoparticles (AgNPs) and zinc oxide nanoparticles (ZnONPs) on zebrafish embryos in aquatic environments. We aimed to characterize the AgNP and ZnONP aggregates in natural waters, such as lakes, reservoirs, and rivers, and to determine whether they are toxic to developing zebrafish embryos. Different toxic effects and mechanisms were investigated by measuring the survival rate, hatching rate, body length, reactive oxidative stress (ROS) level, apoptosis, and autophagy. Spiking AgNPs or ZnONPs into natural water samples led to significant acute toxicity to zebrafish embryos, whereas the level of acute toxicity was relatively low when compared to Milli-Q (MQ) water, indicating the interaction and transformation of AgNPs or ZnONPs with complex components in a water environment that led to reduced toxicity. ZnONPs, but not AgNPs, triggered a significant delay of embryo hatching. Zebrafish embryos exposed to filtered natural water spiked with AgNPs or ZnONPs exhibited increased ROS levels, apoptosis, and lysosomal activity, an indicator of autophagy. Since autophagy is considered as an early indicator of ENP interactions with cells and has been recognized as an important mechanism of ENP-induced toxicity, developing a transgenic zebrafish system to detect ENP-induced autophagy may be an ideal strategy for predicting possible ecotoxicity that can be applied in the future for the risk assessment of ENPs.

The Oxygen-Generating Calcium Peroxide-Modified Magnetic Nanoparticles Attenuate Hypoxia-Induced Chemoresistance in Triple-Negative Breast Cancer.

Cancer response to chemotherapy is regulated not only by intrinsic sensitivity of cancer cells but also by tumor microenvironment. Tumor hypoxia, a condition of low oxygen level in solid tumors, is known to increase the resistance of cancer cells to chemotherapy. Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Due to lack of target in TNBC, chemotherapy is the only approved systemic treatment. We evaluated the effect of hypoxia on chemotherapy resistance in TNBC in a series of in vitro and in vivo experiments. Furthermore, we synthesized the calcium peroxide-modified magnetic nanoparticles (CaO2-MNPs) with the function of oxygen generation to improve and enhance the therapeutic efficiency of doxorubicin treatment in the hypoxia microenvironment of TNBC. The results of gene set enrichment analysis (GSEA) software showed that the hypoxia and autophagy gene sets are significantly enriched in TNBC patients. We found that the chemical hypoxia stabilized the expression of hypoxia-inducible factor 1α (HIF-1α) protein and increased doxorubicin resistance in TNBC cells. Moreover, hypoxia inhibited the induction of apoptosis and autophagy by doxorubicin. In addition, CaO2-MNPs promoted ubiquitination and protein degradation of HIF-1α. Furthermore, CaO2-MNPs inhibited autophagy and induced apoptosis in TNBC cells. Our animal studies with an orthotopic mouse model showed that CaO2-MNPs in combination with doxorubicin exhibited a stronger tumor-suppressive effect on TNBC, compared to the doxorubicin treatment alone. Our findings suggest that combined with CaO2-MNPs and doxorubicin attenuates HIF-1α expression to improve the efficiency of chemotherapy in TNBC.

Novel Application of Magnetite Nanoparticle-Mediated Vitamin D3 Delivery for Peritoneal Dialysis-Related Peritoneal Damage.

PURPOSE: Vitamin D3 is useful for the treatment of peritoneal dialysis (PD)-related peritoneal damage, but its side effects, such as hypercalcemia and vascular calcification, limit its applicability. Thus, we developed vitamin D-loaded magnetic nanoparticles (MNPs) and determined their therapeutic efficacy and side effects in vivo. MATERIALS AND METHODS: Alginate-modified MNPs were combined with 1α, 25 (OH)2D3 to generate vitamin D-loaded nanoparticles. The particles were conjugated with an antibody against peritoneum-glycoprotein M6A (GPM6A). The particles' ability to target the peritoneum was examined following intraperitoneal administration to mice and by monitoring their bio-distribution. We also established a PD animal model to determine the therapeutic and side effects of vitamin D-loaded MNPs in vivo. RESULTS: Vitamin D-loaded MNPs targeted the peritoneum better than vitamin D3, and had the same therapeutic effect as vitamin D3 in ameliorating peritoneal fibrosis and functional deterioration in a PD animal model. Most importantly, the particles reduced the side effects of vitamin D3, such as hypercalcemia and body weight loss, in mice. CONCLUSION: Vitamin D-loaded MNPs could be an ideal future therapeutic option to treat PD-related peritoneal damage.

Advancements in the Blood-Brain Barrier Penetrating Nanoplatforms for Brain Related Disease Diagnostics and Therapeutic Applications.

Noninvasive treatments to treat the brain-related disorders have been paying more significant attention and it is an emerging topic. However, overcoming the blood brain barrier (BBB) is a key obstacle to most of the therapeutic drugs to enter into the brain tissue, which significantly results in lower accumulation of therapeutic drugs in the brain. Thus, administering the large quantity/doses of drugs raises more concerns of adverse side effects. Nanoparticle (NP)-mediated drug delivery systems are seen as potential means of enhancing drug transport across the BBB and to targeted brain tissue. These systems offer more accumulation of therapeutic drugs at the tumor site and prolong circulation time in the blood. In this review, we summarize the current knowledge and advancements on various nanoplatforms (NF) and discusses the use of nanoparticles for successful cross of BBB to treat the brain-related disorders such as brain tumors, Alzheimer's disease, Parkinson's disease, and stroke.

Targeted Paclitaxel by conjugation to iron oxide and gold nanoparticles.

The Fe(3)O(4) nanoparticles, tailored with maleimidyl 3-succinimidopropionate ligands, were conjugated with paclitaxel molecules that were attached with a poly(ethylene glycol) (PEG) spacer through a phosphodiester moiety at the (C-2')-OH position. The average number of paclitaxel molecules/nanoparticles was determined as 83. These nanoparticles liberated paclitaxel molecules upon exposure to phosphodiesterase.

Biomedical microdevices synthesis of iron oxide nanoparticles using a microfluidic system.

The preparation of nanoparticles is essential in the application of many nanotechnologies and various preparation methods have been explored in the previous decades. Among them, iron oxide nanoparticles have been widely investigated in applications ranging from bio-imaging to bio-sensing due to their unique magnetic properties. Recently, microfluidic systems have been utilized for synthesis of nanoparticles, which have the advantages of automation, well-controlled reactions, and a high particle uniformity. In this study, a new microfluidic system capable of mixing, transporting and reacting was developed for the synthesis of iron oxide nanoparticles. It allowed for a rapid and efficient approach to accelerate and automate the synthesis of the iron oxide nanoparticles as compared with traditional methods. The microfluidic system uses micro-electro-mechanical-system technologies to integrate a new double-loop micromixer, two micropumps, and a microvalve on a single chip. When compared with large-scale synthesis systems with commonly-observed particle aggregation issues, successful synthesis of dispersed and uniform iron oxide nanoparticles has been observed within a shorter period of time (15 min). It was found that the size distribution of these iron oxide nanoparticles is superior to that of the large-scale systems without requiring any extra additives or heating. The size distribution had a variation of 16%. This is much lower than a comparable large-scale system (34%). The development of this microfluidic system is promising for the synthesis of nanoparticles for many future biomedical applications.

Comparative efficiencies of photothermal destruction of malignant cells using antibody-coated silica@Au nanoshells, hollow Au/Ag nanospheres and Au nanorods.

Three Au-based nanomaterials (silica@Au nanoshells, hollow Au/Ag nanospheres and Au nanorods) were evaluated for their comparative photothermal efficiencies at killing three types of malignant cells (A549 lung cancer cells, HeLa cervix cancer cells and TCC bladder cancer cells) using a CW NIR laser. Photodestructive efficiency was evaluated as a function of the number of nanoparticles required to destroy the cancer cells under 808 nm laser wavelength at fixed laser power. Of the three nanomaterials, silica@Au nanoshells needed the minimum number of particles to produce effective photodestruction, whereas Au nanorods needed the largest number of particles. Together with the calculated photothermal conversion efficiency, the photothermal efficiency rankings are silica@Au nanoshells > hollow Au/Ag nanospheres > Au nanorods. Additionally, we found that HeLa cells seem to present better heat tolerance than the other two cancer cell lines.

Safe Nanocomposite-Mediated Efficient Delivery of MicroRNA Plasmids for Autosomal Dominant Polycystic Kidney Disease (ADPKD) Therapy.

There is currently no cure for gene mutation-caused autosomal dominant polycystic kidney disease (ADPKD). Over half of patients with ADPKD eventually develop kidney failure, requiring dialysis or kidney transplantation. Current treatment modalities for ADPKD focus on reducing morbidity and mortality from renal and extrarenal complications of the disease. MicroRNA has been shown to be useful in treating ADPKD. This study combines anti-miRNA plasmids and iron oxide/alginate nanoparticles for conjugation with antikidney antibodies. These nanocomposites can specifically target renal tubular cells, providing a potential treatment for ADPKD. Magnetic resonance imaging and in vivo imaging system results show effective targeting of renal cells. Anti-miRNA plasmids released from the nanocomposites inhibit cell proliferation and cyst formation in the PKD cellular and animal models. The results suggest the novel combination of the anti-miRNA plasmids and nanomaterials provides potential clinical implications for ADPKD treatment.

Promising therapeutic effect of thapsigargin nanoparticles on chronic kidney disease through the activation of Nrf2 and FoxO1.

Pathophysiological states cause misfolded protein accumulation in the endoplasmic reticulum (ER). Then, ER stress and the unfolded protein response (UPR) are activated. Targeting ER stress may enhance the adaptive UPR and then protect the cell against pathogenic environments. In the present study, we utilized nanotechnology to synthesize thapsigargin nanoparticles (TG NPs) which induced ER stress and the UPR pathway, to study the role of ER stress and autophagy in chronic kidney disease (CKD). We found that the mRNA levels of ER stress- and autophagy-related molecules were elevated in the renal tissue of CKD patients compared to those of healthy individuals. Furthermore, TG NPs induced the UPR pathway and autophagy in HK-2 human kidney tubular epithelial cells. TG NPs protected HK-2 cells against oxidative stress-induced cell death through the activation of Nrf2 and FoxO1. The siRNA-mediated inhibition of Nrf2 or FoxO1 resulted in enhanced oxidative stress-induced cytotoxicity in HK-2 cells. In a mouse model of adenine diet-induced CKD, TG NPs and KIM-1-TG NPs ameliorated renal injury through the stimulation of ER stress and its downstream pathways. Our findings suggest that the induction of ER stress using pharmacological agents may offer a promising therapeutic strategy for preventing or interfering with CKD progression.

Dental cement's biological and mechanical properties improved by ZnO nanospheres.

Metal oxide nanoparticles are a new class of important materials used in a wide variety of biomedical applications. Bulk zinc oxide (ZnO) particles have been used for temporal or permanent luting cement because of their excellent mechanical strength and biocompatibility. ZnO nanoparticles have distinct optical and antibacterial properties and a high surface-to-volume ratio. We investigated the mechanical and antibacterial properties of luting cement with different ratios of ZnO nanospheres. We showed that luting cement with 5% and 10% ZnO nanospheres was less soluble in low-pH (pH 3) artificial saliva. Antibacterial activity was 40% higher for Streptococcus mutans and 90% higher for Porphyromonas gingivalis when >10% (w/v) of the bulk particles were replaced with ZnO nanospheres in ZnO polycarboxylate cement. ZnO nanospheres were also biocompatible with mammalian cells. Additionally, the compressive strength was 1.2 times greater and the diametral tensile strength was 1.5 times greater for cements with 10% ZnO nanospheres than for conventional ZnO polycarboxylate cement. We propose a new method for improving dental luting cement by integrating it with ZnO nanospheres. This method simultaneously adds their greater antibacterial, mechanical, and acid resistance properties and retains an outstanding degree of biocompatibility.

The Clinical Implication of Vitamin D Nanomedicine for Peritoneal Dialysis-Related Peritoneal Damage.

PURPOSE: Vitamin D is a novel potential therapeutic agent for peritoneal dialysis (PD)-related peritoneal fibrosis, but it can induce hypercalcemia and vascular calcification, which limits its applicability. In this study, we create nanotechnology-based drug delivery systems to investigate its therapeutics and side effects. MATERIALS AND METHODS: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino-(polyethylene glycol)2000] (DSPE-PEG) and L-α-phosphatidylcholine (PC), which packages with 1α,25(OH)2D3, were used to construct vitamin D nanoliposomes. To confirm the function and safety of vitamin D nanoliposomes, peritoneal mesothelial cells were treated with TGF-ß1 and the reverse was attempted using vitamin D nanoliposomes. Antibodies (Ab) against the peritoneum-glycoprotein M6A (GPM6A) Ab were conjugated with vitamin D nanoliposomes. These particles were implanted into mice by intraperitoneal injection and the animals were monitored for the distribution and side effects induced by vitamin D. RESULTS: Vitamin D nanoliposomes were taken up by the mesothelial cells over time without cell toxicity and it also provided the same therapeutic effect in vitro. In vivo study, fluorescent imaging showed vitamin D nanoliposomes allow specific peritoneum target effect and also ameliorate vitamin D side effect. CONCLUSION: Nanoliposomes vitamin D delivery systems for the prevention of PD-related peritoneal damage may be a potential clinical strategy in the future.

Modularly assembled magnetite nanoparticles enhance in vivo targeting for magnetic resonance cancer imaging.

Modularly assembled targeting nanoparticles were synthesized through self-assembly of targeting moieties on surfaces of functional nanoparticles. Specific molecular recognition of nickel nitrilotriacetate on Fe3O4 nanoparticles with hexahistidine tag on RGD4C peptides results in precisely controlled orientation of the targeting peptides. Better selectivity of the self-assembled RGD4C-Fe3O4 nanoparticles targeting oral cancer cells than that achievable through a conventional chemical cross-link strategy was demonstrated by means of atomic absorption spectrometry (AAS). An oral cancer hamster model was applied to reveal specific in vivo targeting and MR molecular imaging contrast in cancer lesions expressing alphavbeta3 integrin. Both AAS and MRI revealed that the self-assembled nanoparticles improved the targeting efficiency and reduced the hepatic uptake as compared with the conventional chemical cross-link particles. We investigated the biosafety, biodistribution, and kinetics of the nanoparticles and found that the nanoparticles were significantly cleared from the liver and kidneys after one week. By recombining the desired targeting moiety and various functional nanoparticles through self-assembly, this new modularly designed platform has the capability of enhancing the efficiency of targeted diagnosis and therapies for a wide spectrum of biomedical applications.