Tetrahedral DNA nanostructures synergize with MnO2 to enhance antitumor immunity via promoting STING activation and M1 polarization

Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn2+ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn2+, we constructed a TDN-MnO2 complex and found that it displayed a much higher efficacy than TDN plus Mn2+ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO2. These findings provide new therapeutic opportunities for cancer therapy.

Research progress on the application of framework nucleic acid in bone regeneration / 华西口腔医学杂志

Framework nucleic acid (FNA) is a set of DNA nanostructures characterized by the framework morphology. It can design rational DNA sequences and follow the principle of complementary base pairing to construct FNA. The recent discovery of FNA constructed by DNA nanotechnology has great application potential in the field of bone regene-ration. It plays a positive role in the osteogenic differentiation of stem cells, bone regeneration, vascular regeneration, neuromodulation, immune regulation, and drug delivery. Here, we reviewed the current study findings on FNA in the field of bone regeneration.

Coating with flexible DNA network enhanced T-cell activation and tumor killing for adoptive cell therapy

Adoptive cell therapy (ACT) is an emerging powerful cancer immunotherapy, which includes a complex process of genetic modification, stimulation and expansion. During these

Research progress in tumor microenvironmentally modulating nanostructures / 药学学报

Tumor microenvironment (TME) is a complex comprehensive system composed of immune cells, inflammatory cells, tumor-associated fibroblasts, microvessels, and various cytokines and chemokines. As the living environment of tumor cells, it's closely related to the occurrence, metastasis, and recurrence of tumors. The characteristics of tumor microenvironment include: weakly acidic environment, low oxygen, high concentration of reactive oxygen species (ROS) and reducing substances, immunosuppression, etc. A weakly acidic environment favors metastasis of tumor cells, hypoxia is conducive to the emergence of drug resistance, high concentration of ROS and reducing substances are beneficial for tumor treatment, and immunosuppressiveness facilitates immune escape. With the rapid development of nanotechnology, more and more nanostructures have been reported to achieve tumor treatment by regulating the tumor microenvironment. This review summarizes recent advances in the nanostructures used to regulate tumor microenvironment through changing elements, including hydrogen-ion concentration (pH), the concentration of oxygen (O2) and reactive oxygen species, and the activity of immune cells. Moreover, research directions in the future are pointed out in this review.

Study on tailoring the nanostructured surfaces of cuttlefish bone transformed hydroxyapatite porous ceramics and its effect on osteoblasts / 中国修复重建外科杂志

Objective: To investigate the formation of nanostructure on cuttlefish bone transformed hydroxyapatite (CB-HA) porous ceramics and the effects of different nanostructures on the osteoblasts adhesion, proliferation, and alkaline phosphatase (ALP) expression. Methods: The cuttlefish bone was shaped as plate with diameter of 10 mm and thickness of 2 mm, filled with water, and divided into 4 groups. The CB-HA in groups 1-4 were mixed with different phosphorous solutions and then placed in an oven at 120℃ for 24 hours. In addition, the samples in group 4 were further sintered at 1 200℃ for 3 hours to remove nanostructure as controls. The chemical composition of CB-HA were analyzed by X-ray diffraction spectroscopy, Fourier transform infrared spectrum, and inductively coupled plasma (ICP). The physical structure was analyzed using scanning electron microscopy, specific surface tester, and porosity tester. The MC3T3-E1 cells of 4th generation were co-cultured with 4 groups of CB-HA. After 1 day, the morphology of the cells was observed under scanning electron microscopy. After 1, 3, and 7 days, the cell proliferation was analyzed by MTT assay. After 7 and 14 days, the ALP expression was measured by pNPP method. Results: X-ray diffraction spectrum showed that the four nanostructures of CB-HA were made of hydroxyapatite. The infrared absorption spectrum showed that the infrared absorption peak of CB-HA was consistent with hydroxyapatite. ICP showed that the ratio of calcium to phosphorus of all CB-HA was 1.68-1.76, which was consistent with hydroxyapatite. Scanning electron microscopy observation showed that the nanostructure on the surface of CB-HA in groups 1-3 were large, medium, and small cluster-like structures, respectively, and CB-HA in group 4 had no obvious nanostructure. There were significant differences in the specific surface areas between groups ( P0.05). Compared with group 4, groups 1-3 have more pores with pore size less than 50 nm. After co-cultured with osteoblasts, scanning electron microscopy observation and MTT assay showed that the cells on groups 2 and 3 adhered and proliferated better and had more ALP expression than that on groups 1 and 4 ( P<0.05). Conclusion: The size of cluster-like nanostructure on the surface of CB-HA can be controlled by adjusting the concentration of ammonium ions in the phosphorous solution, and the introduction of small-sized cluster-like nanostructure on the surface of CB-HA can significantly improve the cell adhesion, proliferation, and ALP expression of the material which might be resulted from the enlarged surface area.

Comparative Study on Pharmacokinetics of Brucine and Its Nanostructure Lipid Carrier in Rats / 中国药房

OBJECTIVE:To establish a method for the determination of brucine concentration in plasma of rats,and to compare the pharmacokinetic differences between brucine and its nanostructure lipid carrier (NLC) in rats. METHODS:Sixteen male SD rats were randomly divided into brucine NLC solution group and brucine solution group(using normal saline as solvent, and containing brucine 1.28 mg/mL),with 8 rats in each group. They were given relevant solution 10 mg/kg via tail vein. Blood sample 0.5 mL was collected from fundus venous plexus capillary before medication and 15,20,30,40,45,60,90,120,150, 180,210,240,480 min after medication. HPLC method was adopted. The determination was performed on Dikma C18column with mobile phase consisted of methanol-water containing acetic acid and triethylamine(30∶70,V/V)at the flow rate of 1 mL/min. The detection wavelength was set at 265 nm,and column temperature was 30 ℃. Sample size was 10 μ L. Pharmacokinetic parameters of rats in 2 groups were calculated by using DAS 2.0 software,and the difference of them were compared by F test. RESULTS:The linear range of brucine plasma concentration were 1.03-66.00 μg/mL(R2＝0.999 6);the limit of quantitation was 1.03 μg/mL,and lowest detection limit was 0.515 μg/mL. RSDs of intra-day and inter-day were lower than 5%;method recoveries were 84.90%-100.88%, extraction recoveries were 80.60%-91.98%(all RSDs were lower than 10%). Average plasma concentration-time curve of single administration of brucine NLC solution and brucine solution were all in line with two-compartment model after medication via tail vein. The pharmacokinetic parameters included t1/2αwere(0.24±0.11)and(0.06± 0.03)h;t1/2 βwere (2.90 ± 0.22) and (0.57 ± 0.32)h;AUC0-twere (88.00 ± 6.98) and (28.50 ± 5.87)μg·h/mL;AUC0-∞were (109.96±7.99)and(45.06±6.66)μg·h/mL. Compared with brucine solution group,t1/2 α,t1/2 β,AUC0-tand AUC0- ∞of brucine NLC solution group were increased significantly;while CL, k10and k12were decreased significantly, with statistical significance (P＜0.05 or P＜0.01). There was no statistical significance in k21between 2 groups (P＞0.05). CONCLUSIONS: Established HPLC method is simple, specific,sensitive,precise and highly recoverable. It can be used for the determination of plasma concentration and phamacokinetic study of brucine in rats. After brucine NLC is prepared,the pharmacokinetic parameters of brucine change significantly;retention time of brucine is significantly prolonged and the clearance rate decreases significantly.

Uses And Prospects Of Nanotechnology In Food

Use of nanotechnology in food science to increase/alter nutritive value and shelf life of food has provided lot of dimensions in research to meet out the need of food for globally growing population. Fortification of food with nano nutrients and also the use of nanotechnology to enrich the nutritive values of food have explored avenues in nutritional science for the production of highly nutritive food products required for different diseases, gender based requirements, age wise need and variable requirements under different climatic conditions. On the other hand discussions have also initiated about the safety of nano food for consumption, its assimilation in human system and its acceptance by human body. This review briefs the use of nanotechnology in food industry for improvising the quality and quantity of food with keeping an eye on health and environmental concerns.

Effect of Serum on Cellular Uptake of TetrahedralDeoxyribonucleic Acid Nanostructure / 分析化学

In the present study, the effect of serum (fetal bovine serum, FBS) on cellular uptake behaviors of DNA tetrahedron (TDNs) was investigated.Fluorescence-labeled TDNs were synthesized by self-assembly and purified with HPLC to achieve TDNs product with purity of 95%.By means of flow cytometry and confocal microscopy, the kinetics of TDNs endocytosis in HeLa cells in the presence or absence of FBS was compared.The results showed that TDNs remained intact in complete medium and cell lysate for more than 12 hours.FBS increased the amount of internalized TDNs in HeLa cells, whereas it did not change the route of caveolin-dependent endocytosis.Herein, our study provided a new insight into the effects of biomolecules on the interaction between cells and DNA nanostructures, which helped the future development of DNA-based intracellular nanocarriers.

Structural analysis of a ligatured rat sciatic nerve in the ex vivo state using synchrotron small-angle X-ray scattering (SAXS)

BACKGROUND: To understand the fundamentals of neural tissue injury, experiments on the nano-structured nerve system of animals are essential. This study was designed to reveal the nanostructure changes of an isolated ligatured rat sciatic nerve using the synchrotron small-angle X-ray scattering (SAXS) technique. METHODS: Male Sprague-Dawley rats (weighing approximately 250 grams) were used in this study. The SAXS patterns of 1 week after ligatured nerves (N = 5) and the normal sciatic nerves (N = 5) for the control were acquired after extracted approximately 15 mm before the experiment. Experiments were conducted at the 4C1 beam line at the Pohang Accelerator Laboratory in Korea. The exposure time was 60 sec, and 8 to 12 images per sample were acquired in 0.5 mm intervals, including the regions above, around and below the ligatured position. RESULTS: The periodic peaks of the myelin sheath and the interfibrillar space of collagen completely disappeared at the ligatured position. Farther from the ligatured point, weak and quite different SAXS patterns were observed for the myelin sheath and interfibrillar space. However, the collagen fiber peaks appeared at all positions, although they were weaker near the ligatured position. CONCLUSIONS: The ligature treatment totally destroyed the myelin sheath and interfibrillar space of collagen. In addition, retrograde degeneration developed 2 mm above the ligatured site. The myelin sheath and interfibrillar space of collagen were damaged 6 mm below the ligatured site. However, the collagen fiber structure was not significantly affected by the ligature, indicating a much different structural organization.

Preparation and in vitro and in vivo evaluation of folate-BSA-coated cationic nanostructure lipid carriers / 中国药科大学学报

@#Folic acid(FA)was conjugated with bovine serum albumin(BSA)to form targeting material. BSA-coated cationic nanostructure lipid carriers(BSA-cNLCs)and folate-BSA-coated cationic nanostructure lipid carriers(FA-BSA-cNLCs)were prepared by film dispersion. The particle sizes of BSA-cNLCs and FA-BSA-cNLCs were 81. 4 nm and 79. 8 nm, while their Zeta potentials were +5. 12 mV and +3. 74 mV. Both nanostructure lipid carriers showed spherical shape. Paclitaxel encapsulation efficiency of them were more than 97%, with drug loading efficiency of about 3. 7%. In vitro experiments confirmed that the uptake of FA-BSA-cNLCs by overexpressed folate receptor SKOV3 cells was significantly higher than that of BSA-cNLCs, demonstrating that FA-BSA-cNLCs were obviously targeted to SKOV3. Blood and tumor pharmacokinetics showed that there was no significant differences between BSA-cNLCs and FA-BSA-cNLCs. This suggested that modified FA on the surface of the preparation had no effect on its in vivo behavior. Tumor inhibition of BSA-cNLCs and FA-BSA-cNLCs were 72. 08% and 80. 75%, repectively, which indicateds that FA-BSA-cNLCs improve anticancer efficacy in vitro and in vivo, and that it could be a potential preparation for the treatment of cancer.

Recent developments in mechanics of biological materials: A brief review / 医用生物力学

As a rapidly developing area in biomechanics, mechanics of biological materials aims to investigate the fundamental relationship between functions, properties, structures, and compositions of various natural biological materials at different length scales and the underlying physical mechanisms through experimental research and theoretical analysis, and to provide inspirations from the splendid living world for the biomimetic design of new materials. In this paper, some recent achievements, mainly made by Chinese scholars in this field, are briefly reviewed, including the stiffening and toughening mechanisms of such biological composites as nacres and horns, the relation between the surface wetting behavior and the micro/nanostructures, and some relevant biomimetic applications as well. The contents of seven invited papers published in this special issue are also introduced.

Local thermal effect of RF on nanogold-labeled RNase / 第三军医大学学报

Objective To establish a biological model with nanostructure and to investigate the characteristics of the thermal conduction by radio frequency electromagnetic radiation upon the model for the exploration of the possible mechanism of microwave non thermal effect. Methods The prepared nanogold labeled RNase S sample was analyzed by routine hydrolytic ability of poly c and CD spectroscopy. After confirmation of the successful recombination of the enzymatic structure and the recovery of the enzyme activity, thermal effects of RF on the sample, water and air were compared. Results The biological model designed and prepared by us satisfactorily simulated the native RNase A in both recovery of enzyme activity and conformation. Air sample in air bathing possessed an exponent decreasing function for thermal dispersion and an exponent increasing function for RF thermal effect. The redistilled water sample had a linear increasing function for RF thermal effect. Meanwhile, nanogold labeled RNase S in water bathing kept constant for RF thermal effect. Conclusion Micro eddy current local heating might occur in microstructure consisting of nanometal cluster. A biological macromolecule with nanostructure, acting as a source of thermal radiation and conduction, might resonantly interact with some changeable domains nearby, so the biological model keeps isothermal during RF heating. This may be a possible mechanism of nonthermal effect for microwave and other physical factors.