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Nanodiamonds have been discovered as a new exogenous material source in biomedical applications. As a new potent form of nanodiamond (ND), polyamidoamine-decorated nanodiamonds (PAMAM-NDs) were prepared for E7 or E6 oncoprotein-suppressing siRNA gene delivery for high risk human papillomavirus-induced cervical cancer, such as types 16 and 18. It is critical to understand the physicochemical properties of siRNA complexes immobilized on cationic solid ND surfaces in the aspect of biomolecular structural and conformational changes, as the new inert carbon material can be extended into the application of a gene delivery vector. A spectral study of siRNA/PAMAM-ND complexes using differential scanning calorimetry and circular dichroism spectroscopy proved that the hydrogen bonding and electrostatic interactions between siRNA and PAMAM-NDs decreased endothermic heat capacity. Moreover, siRNA/PAMAM-ND complexes showed low cell cytotoxicity and significant suppressing effects for forward target E6 and E7 oncogenic genes, proving functional and therapeutic efficacy. The cellular uptake of siRNA/PAMAM-ND complexes at 8 h was visualized by macropinocytes and direct endosomal escape of the siRNA/PAMAM-ND complexes. It is presumed that PAMAM-NDs provided a buffering cushion to adjust the pH and hard mechanical stress to escape endosomes. siRNA/PAMAM-ND complexes provide a potential organic/inorganic hybrid material source for gene delivery carriers.

Novel nanodiamond–gold nanocomposites (NDAus) are prepared, and their oxidative catalytic activity is examined. Gold nanoparticles are deposited on carboxylated nanodiamonds (NDs) by in situ chemical reduction of gold precursor ions to produce NDAus, which exhibit catalytic activity for the oxidation of o-phenylenediamine in the presence of hydrogen peroxide similarly to a peroxidase. This remarkable catalytic activity is exhibited only by the gold nanoparticle-decorated NDs and is not observed for either Au nanoparticles or NDs separately. Kinetic oxidative catalysis studies show that NDAus exhibit a ping-pong mechanism with an activation energy of 93.3 kJ mol–1, with the oxidation reaction rate being proportional to the substrate concentration. NDAus retain considerable activity even after several instances of reuse and are compatible with a natural enzyme, allowing the detection of xanthine using cascade catalysis. Association with gold nanoparticles makes NDs a good carbonic catalyst due to charge transfer at the metal–carbon interface and facilitated substrate adsorption. The results of this study suggest that diverse carbonic catalysts can be obtained by interfacial incorporation of various metal/inorganic substances.

Photoacoustic activity is the generation of an ultrasonic signal via thermal expansion or bubble formation, stimulated by laser irradiation. Photoacoustic nanoplatforms have recently gained focus for application in bioelectric interfaces. Various photoacoustic material types have been evaluated, including gold nanoparticles, semiconductive π-conjugating polymers (SP), etc. In this study, surfactant-free methoxy-polyethylene glycol-co-polypyrrole copolymer (mPEG-co-PPyr) nanoparticles (NPs) and mPEG-co-PPyr NP/molybdenum disulfide (mPEG-co-PPyr/MoS2) nanocomposites (NCs) were prepared and their photoacoustic activity was demonstrated. The mPEG-co-PPyr NPs and mPEG-co-PPyr/MoS2NCs both showed photoacoustic signal activity. The mPEG-co-PPyr/MoS2NCs presented a higher photoacoustic signal amplitude at 700 nm than the mPEG-co-PPyr NPs. The enhanced photoacoustic activity of the mPEG-co-PPyr/MoS2NCs might be attributed to heterogeneous interfacial contact between mPEG-co-PPyr and the MoS2nanosheets due to complex formation. Laser ablation of MoS2might elevate the local temperature and facilitate the thermal conductive transfer in the mPEG-co-PPyr/MoS2NCs, amplifying PA signal. Our study, for the first time, demonstrates enhanced PA activity in SP/transition metal disulfide (TMD) composites as photoacoustic nanoplatforms.

Nanodiamonds (NDs) with 5 nm crystalline structures have been recognized as emerging carbon delivery vehicles due to their biocompatible inertness, high surface-to-volume ratio, and energy absorbance properties. In this study, carboxylated nanodiamond (ND–COOH) was reduced to hydroxylated nanodiamond (ND–OH) for stable and pH-independent colloidal dispersity. The poorly water-soluble paclitaxel (PTX) was physically loaded into ND–OH clusters, forming amorphous PTX nanostructure on the interparticle nanocage of the ND substrate. Stable physical PTX loading onto the ND substrate with stable colloidal stability showed enhanced PTX release. ND–OH/PTX complexes retained the sustained release of PTX by up to 97.32% at 70 h, compared with the 47.33% release of bare crystalline PTX. Enhanced PTX release from ND substrate showed low cell viability in Hela, MCF-9, and A549 cancer cells due to sustained release and stable dispersity in a biological aqueous environment. Especially, the IC50values of ND–OH/PTX complexes and PTX in Hela cells were 0.037 μg/mL and 0.137 μg/mL, respectively. Well-dispersed cellular uptake of suprastructure ND–OH/PTX nanocomplexes was directly observed from the TEM images. ND–OH/PTX nanocomplexes assimilated into cells might provide convective diffusion with high PTX concentration, inducing initial necrosis. This study suggests that poorly water-soluble drugs can be formulated into a suprastructure with ND and acts as a highly concentrated drug reservoir directly within a cell.

2,6,6-Trimethylbicyclo[3.1.1]hept-2-ene (α-Pinene) is an organic compound of the terpene class found in the essential oil of many plants. In this study, the inhibitory effect of α-pinene on tumor invasion in highly metastatic MDA-MB-231 human breast cancer cells was evaluated. α-Pinene inhibited tumor necrosis factor (TNF)-α-induced invasiveness of MDA-MB-231 cells as revealed by three-dimensional spheroid invasion assay. Further analysis showed that α-pinene reduced TNFα-induced matrix metalloproteinase-9 gene promoter activation and mRNA expression in a dose-dependent manner. In addition, α-pinene treatment attenuated TNFα-induced nuclear factor κB (NF-κB) activation and NF-κB-dependent transcriptional activity. These results suggest that α-pinene has a significant effect on the inhibition of tumor invasion and may potentially be developed into an anti-metastatic drug.

With increased esthetic needs, orthodontics is an indispensable medical treatment in dentistry, and transparent clear overlay appliances (COAs) are in general use to fix teeth. However, COAs are easily worn out because of the lack of durability. Here, we applied a nanofilm onto COAs using urushiol (U), a durable coating material from plant via a layer-by-layer assembly technique. In particular, polymerized urushiol (PU) provided COAs with higher mechanical strength in the large-scale assessment, lower cytotoxicity, and intrinsic hydrophobicity for antimicrobial use. In this report, we inceptively attempted to functionalize COAs with nanofilm for advanced biomedical use.

The current study tested the hypothesis that removal of maltose binding protein (MBP) from recombinant antigen used for plate coating would improve the specificity of a commercial Anaplasmaantibody competitive enzyme-linked immunosorbent assay (cELISA). The number of 358 sera with significant MBP antibody binding (≥30%I) in Anaplasma-negative herds was 139 (38.8%) when tested using the recombinant major surface protein 5 (rMSP5)-MBP cELISA without MBP adsorption. All but 8 of the MBP binders were rendered negative (<30%I) using the commercial rMSP5-MBP cELISA with MBP adsorption, resulting in 97.8% specificity. This specificity was higher than some previous reports, so to improve the specificity of the commercial cELISA, a new recombinant antigen designated rMSP5–glutathione S-transferase (GST) was developed, eliminating MBP from the antigen and obviating the need for MBP adsorption. Using the rMSP5-GST cELISA, only 1 of 358 Anaplasma-negative sera, which included the 139 sera with significant (≥30%I) MBP binding in the rMSP5-MBP cELISA without MBP adsorption, was positive. This resulted in an improved diagnostic specificity of 99.7%. The rMSP5-GST cELISA without MBP adsorption had comparable analytical sensitivity to the rMSP5-MBP cELISA with MBP adsorption and had 100% diagnostic sensitivity when tested with 135 positive sera defined by nested polymerase chain reaction. Further, the rMSP5-GST cELISA resolved 103 false-positive reactions from selected sera with possible false-positive reactions obtained using the rMSP5-MBP cELISA with MBP adsorption and improved the resolution of 29 of 31 other sera. In summary, the rMSP5-GST cELISA was a faster and simpler assay with higher specificity, comparable sensitivity, and improved resolution in comparison with the rMSP5-MBP cELISA with MBP adsorption.

No Abstract

Durch die Koaleszenz und Fusionvon Kohlendioxidnanobläschen in einem Tumor entstehen Mikrobläschen, die mit Ultraschall sichtbar gemacht werden können (siehe Bild). Die Bläschen stammen von Gas freisetzenden polymeren Nanopartikeln mit einem Überzug aus hydrophobisiertem Chitosan. Die Hydrolyse des Polymers Poly(BL‐PO) mit einem bioabbaubaren Rückgrat und einer Carbonatseitenkette setzt Kohlendioxid frei.

1,3-Dipropyl-8-cyclopentyl xanthine (DPCPX) is a highly selective antagonist of the adenosine A1receptor (A1R). The A1R mediates mitogenic effects of adenosine in coronary artery smooth muscle cells (CASMC). DPCPX plays a role as an antimitogen and reduces CASMC proliferation by the blockage of A1R. A drug-eluting stent (DES) loaded with DPCPX was prepared. The water solubility of DPCPX is 1.6 μg/mL at pH 3−9, and 38.1 ± 2.3 μg/mL at pH 11. A series of DPCPX-eluting stents were formulated in polyurethane (PU) films with different dose densities and film thicknesses. The release of DPCPX from the PU-coated stents was nearly linear. The release rate and duration were effectively controlled by adjusting the film thickness with the same drug concentration. The eluted DPCPX from the PU films was effective in preventing CASMC proliferation, regardless of stimulation by 2-chloro-N-6-cyclopentyladenosine (CCPA), a highly selective A1R agonist. A1R specific antagonist DPCPX was effective in preventing CASMC proliferation and holds great promise for intracoronary delivery from DESs to test the role of the A1R signaling pathway for prevention of in-stent restenosis.

Advances in nanotechnology have contributed to the development of novel nanoparticles that enable the tumor‐specific delivery of imaging probes and therapeutic agents in cancer imaging and therapy. Nanobiotechnology combines nanotechnology with molecular imaging, which has led to the generation of new multifunctional nanoparticles for cancer imaging and therapy. Multifunctional nanoparticles hold great promise for the future of cancer treatment because they can detect the early onset of cancer in each individual patient and deliver suitable therapeutic agents to enhance therapeutic efficacy. The combination of tumor‐targeted imaging and therapy in an all‐in‐one system provides a useful multimodal approach in the battle against cancer. Novel multifunctional nanoparticles thus offer a new avenue in the application of personalized medicine in the near future. Herein, new trends and the significance of novel multifunctional nanoparticles in cancer imaging and therapy are reviewed.

We developed a novel pH- and thermo-sensitive hydrogel as a scaffold for autologous bone tissue engineering. We synthesized this polymer by adding pH-sensitive sulfamethazine oligomers (SMOs) to both ends of a thermo-sensitive poly(ɛ-caprolactone-co-lactide)–poly(ethylene glycol)–poly(ɛ-caprolactone-co-lactide) (PCLA-PEG-PCLA) block copolymer, yielding a pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer. The synthesized block copolymer solution rapidly formed a stable gel under physiological conditions (pH 7.4 and 37°C), whereas it formed a sol at pH 8.0 and 37°C, making it injectable. This pH/thermo-sensitive hydrogel exhibited high biocompatibility in a Dulbecco's modified Eagle's medium extract test. Under physiological conditions, the hydrogel easily encapsulated human mesenchymal stem cells (hMSCs) and recombinant human bone morphogenetic protein-2 (rhBMP-2), with encapsulating efficiencies of about 90% and 85%, respectively. To assay for ectopic bone formation in vivo, we subcutaneously injected a polymer solution containing hMSCs and rhBMP-2 into the back of mice, after which we could observe hMSC differentiation for up to 7 weeks. Histological studies revealed mineralized tissue formation and high levels of alkaline phosphatase activity in the mineralized tissue. Therefore, this pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer demonstrated potential as an injectable scaffold for bone tissue engineering, with in situformation capabilities.