Tailored design of NHS-SS-NHS cross-linked chitosan nano-hydrogels for enhanced anti-tumor efficacy by GSH-responsive drug release.

The traditional chemotherapeutic agents' disadvantages such as high toxicity, untargeting and poor water solubility lead to disappointing chemotherapy effects, which restricts its clinical application. In this work, novel size-appropriate and glutathione (GSH)-responsive nano-hydrogels were successfully prepared via the active ester method between chitosan (containing -NH2) and cross-linker (containing NHS). Especially, the cross-linker was elaborately designed to possess a disulfide linkage (SS) as well as two terminal NHS groups, namely NHS-SS-NHS. These functionalities endowed chitosan-based cross-linked scaffolds with capabilities for drug loading and delivery, as well as a GSH-responsive mechanism for drug release. The prepared nano-hydrogels demonstrated excellent performance applicable morphology, excellent drug loading efficiency (∼22.5%), suitable size (∼100 nm) and long-term stability. The prepared nano-hydrogels released over 80% doxorubicin (DOX) after incubation in 10 mM GSH while a minimal DOX release less than 25% was tested in normal physiological buffer (pH = 7.4). The unloaded nano-hydrogels did not show any apparent cytotoxicity to A 549 cells. In contrast, DOX-loaded nano-hydrogels exhibited marked anti-tumor activity against A 549 cells, especially in high GSH environment. Finally, through fluorescent imaging and flow cytometry analysis, fluorescein isothiocyanate-labeled nano-hydrogels show obvious specific binding to the GSH high-expressing A549 cells and nonspecific binding to the GSH low-expressing A549 cells. Therefore, with this cross-linking approach, our present finding suggests that cross-linked chitosan nano-hydrogel drug carrier improves the anti-tumor effect of the A 549 cells and may serve as a potential injectable delivery carrier.

Double base mismatches mediated catalytic hairpin assembly for enzyme-free single-base mutation detection: integrating signal recognition and amplification in one.

Single nucleotide polymorphism (SNP) biosensors are emerging rapidly for their promising applications in human disease prevention diagnosis, treatment, and prognosis. However, it remains a bottleneck in equipping simple and stable biosensors with the traits of high sensitivity, non-enzyme, and low cost. Double base mismatches mediated chain displacement reactions have attracted fascinating advantages of tailorable thermodynamics stability, non-enzyme, and excellent assembly compliance to involvement in SNP identification. As the base mismatch position and amount in DNA sequence can be artificially adjusted, it provides plenty of selectivity and specificity for exploring perfect biosensors. Herein, a biosensor with double base mismatches mediated catalytic hairpin assembly (CHA) is designed via one base mismatch in the toehold domain and the other base mismatch in the stem sequence of hairpin 1 (H1) by triggering CHA reaction to achieve selective amplification of the mutation target (MT) and fluorescence resonance energy transfer (FRET) effect that is composed of Cy3 and Cy5 terminally attached H1 and hairpin 2 (H2). Depending on the rationally designed base mismatch position and toehold length, the fabricated biosensors show superior SNP detection performance, exhibiting a good linearity with high sensitivity of 6.6 fM detection limit and a broad detection abundance of 1%. The proposed biosensor can be used to detect the KRAS mutation gene in real samples and obtain good recoveries between 106 and 116.99%. Remarkably, these extendible designs of base mismatches can be used for more types of SNP detection, providing flexible adjustment based on base mismatch position and toehold length variations, especially for their thermodynamic model for DNA-strand displacement reactions.

Investigation of Mechanical and Shrinkage Performance for Large-Size Cement-Stabilized Aggregates.

Cement-stabilized macadam materials are widely utilized as semi-rigid base materials in road construction. However, conventional cement-stabilized macadam (CCSM) bases often develop shrinkage cracks during early construction and maintenance due to variations in humidity and temperature. Shrinkage cracks can subsequently result in reflective cracks in the asphalt pavement, significantly reducing the overall service life of the road. This study systematically evaluates the shrinkage and mechanical properties of large-size cement-stabilized macadam (LSCSM). Initially, the mix proportion for LSCSM is determined using the Bailey method. Subsequently, an experimental design based on the response surface method is implemented to comprehensively investigate various properties, including unconfined compressive strength, compressive rebound modulus, flexural strength, and the durability aspects of early drying shrinkage and temperature shrinkage through laboratory experiments. Further, the performance differences between CCSM and LSCSM are analyzed comparatively. The findings reveal that the compressive strength of LSCSM surpasses that of CCSM, albeit with comparatively lower compressive rebound modulus and flexural strength. LSCSM demonstrates a unique blend of characteristics, exhibiting traits of both semi-rigid and flexible materials. Furthermore, LSCSM exhibits favorable crack resistance properties, as evidenced by lower dry shrinkage strain, average dry and temperature shrinkage coefficient compared to CCSM. The proposed LSCSM in this study effectively reduces cement dosage and enhances the crack resistance performance of base materials.

Exercise-induced endothelial Mecp2 lactylation suppresses atherosclerosis via the Ereg/MAPK signalling pathway.

BACKGROUND AND AIMS: Lactylation, a recently identified post-translational modification (PTM), plays a central role in the regulation of multiple physiological and pathological processes. Exercise is known to provide protection against cardiovascular disease. However, whether exercise-generated lactate changes lactylation and is involved in the exercise-induced attenuation of atherosclerotic cardiovascular disease (ASCVD) remains unclear. The purpose of this study was to investigate the effects and mechanisms of exercise-induced lactylation on ASCVD. METHODS AND RESULTS: Using the high-fat diet-induced apolipoprotein-deficient mouse model of ASCVD, we found that exercise training promoted Mecp2 lysine lactylation (Mecp2k271la); it also decreased the expression of vascular cell adhesion molecule 1 (Vcam-1), intercellular adhesion molecule 1 (Icam-1), monocyte chemoattractant protein 1 (Mcp-1), interleukin (IL)-1ß, IL-6, and increased the level of endothelial nitric oxide synthase (Enos) in the aortic tissue of mice. To explore the underlying mechanisms, mouse aortic endothelial cells (MAECs) were subjected to RNA-sequencing and CHIP-qPCR, which confirmed that Mecp2k271la repressed the expression of epiregulin (Ereg) by binding to its chromatin, demonstrating Ereg as a key downstream molecule for Mecp2k271la. Furthermore, Ereg altered the mitogen-activated protein kinase (MAPK) signalling pathway through regulating the phosphorylation level of epidermal growth factor receptor, thereby affecting the expression of Vcam-1, Icam-1, Mcp-1, IL-1ß, IL-6, and Enos in ECs, which in turn promoted the regression of atherosclerosis. In addition, increasing the level of Mecp2k271la by exogenous lactate administration in vivo also inhibits the expression of Ereg and the MAPK activity in ECs, resulting in repressed atherosclerotic progression. CONCLUSIONS: In summary, this study provides a mechanistic link between exercise and lactylation modification, offering new insight into the anti-atherosclerotic effects of exercise-induced PTM.

Controlled growth of titanium dioxide nanotubes for doxorubicin loading and studies of in vitro antitumor activity.

Titanium dioxide (TiO2) materials are suitable for use as drug carriers due to their natural biocompatibility and nontoxicity. The aim of the study presented in this paper was to investigate the controlled growth of TiO2 nanotubes (TiO2 NTs) of different sizes via an anodization method, in order to delineate whether the size of NTs governs their drug loading and release profile as well as their antitumor efficiency. TiO2 NTs were tailored to sizes ranging from 25 nm to 200 nm according to the anodization voltage employed. The TiO2 NTs obtained by this process were characterized using scanning electron microscopy, transmission electron microscopy, and dynamic light scattering The larger TiO2 NTs exhibited greatly improved doxorubicin (DOX)-loading capacity (up to 37.5 wt%), which contributed to their outstanding cell-killing ability, as evidenced by their lower half-maximal inhibitory concentration (IC50). Comparisons were carried out of cellular uptake and intracellular release rates of DOX for large and small TiO2 NTs loaded with DOX. The results showed that the larger TiO2 NTs represent a promising therapeutic carrier for drug loading and controlled release, which could improve cancer treatment outcomes. Therefore, TiO2 NTs of larger size are useful substances with drug-loading potency that may be used in a wide range of medical applications.

Study on Rheological and Mechanical Properties of Rock-Compound-Additive-Modified Asphalt and Its Mixture.

Rutting is one of the most widespread and severe diseases in the service life of asphalt pavement. Enhancing the high-temperature rheological properties of pavement materials is one of the valid measures that can be used to solve rutting disease. In this research, the laboratory tests were carried out to compare the rheological properties of the different asphalts (including neat asphalt (NA), styrene-butadiene-styrene asphalt (SA), polyethylene asphalt (EA), and rock-compound-additive-modified asphalt (RCA)). Then, the mechanical behaviors of different asphalt mixtures were investigated. The results show that the rheological properties of modified asphalt with a 15% rock compound additive performed better compared with the other forms of modified asphalt. The dynamic shear modulus of 15% RCA is significantly higher than the other three asphalt binders, which is 8.2 times, 8.6 times, and 14.3 times that of the NA, SA, and EA at a temperature of 40 °C, respectively. After adding the rock compound additive, the compressive strength, splitting strength, and fatigue life of the asphalt mixtures were significantly enhanced. The results of this research have practical significance for new materials and structures to improve asphalt pavement resistance to rutting.

Exercise Mitigates Endothelial Pyroptosis and Atherosclerosis by Downregulating NEAT1 Through N6-Methyladenosine Modifications.

BACKGROUND: The benefits of exercise on the cardiovascular system are widely recognized; however, the underlying mechanisms are unknown. Here, we report the effect of the long noncoding RNA NEAT1 (nuclear paraspeckle assembly transcript 1), which is regulated by exercise, on atherosclerosis development after N6-methyladenosine (m6A) modifications. METHODS: Using clinical cohorts and NEAT1-/- mice, we determined the exercise-mediated expression and role of NEAT1 in atherosclerosis. To investigate the mechanism of epigenetic modification of NEAT1 regulated by exercise, we identified METTL14 (methyltransferase-like 14)-a key m6A modification enzyme under exercise-and found that METTL14 alters the expression and role of NEAT1 through m6A modification and elucidated the specific mechanism of METTL14 in vitro and in vivo. Finally, the NEAT1 downstream regulatory network was investigated. RESULTS: We found that NEAT1 expression was downregulated with exercise and that downregulation of NEAT1 was an important factor in the improvement of atherosclerosis with exercise. Exercise-mediated loss of function of NEAT1 can delay atherosclerosis. Mechanistically, we showed that exercise induced a significant downregulation of m6A modification and METTL14, which binds to the m6A sites of NEAT1 and promotes NEAT1 expression through subsequent YTHDC1 (YTH domain-containing 1) recognition to promote endothelial pyroptosis. Furthermore, NEAT1 induces endothelial pyroptosis by binding KLF4 (Kruppel-like factor 4) to promote the transcriptional activation of the key pyroptotic protein NLRP3 (NOD-like receptor thermal protein domain-associated protein 3), whereas exercise can attenuate NEAT1-mediated endothelial pyroptosis to improve atherosclerosis. CONCLUSIONS: Our study of NEAT1 provides new insights into the improvement of atherosclerosis by exercise. This finding demonstrates the role of exercise-mediated NEAT1 downregulation in atherosclerosis while expanding our understanding of the mechanisms by which exercise regulates long noncoding RNA function through epigenetic modifications.

Comammox Nitrospira Bacteria Are Dominant Ammonia Oxidizers in Mainstream Nitrification Bioreactors Emended with Sponge Carriers.

Complete ammonia oxidation (i.e., comammox) is a newly discovered microbial process performed by a subset of the Nitrospira genus, and this unique microbial process has been ubiquitously detected in various wastewater treatment units. However, the operational conditions favoring comammox prevalence remain unclear. In this study, the dominance of comammox Nitrospira in four sponge biofilm reactors fed with low-strength ammonium (NH4+ = 23 ± 3 mg N/L) wastewater was proved by coupling 16S rRNA gene amplicon sequencing, quantitative polymerase chain reaction (qPCR), and metagenomic sequencing. The results showed that comammox Nitrospira dominated in the nitrifying guild over canonical ammonia-oxidizing bacteria (AOB) constantly, despite the significant variation in the residual ammonium concentration (0.01-15 mg N/L) under different sets of operating conditions. This result indicates that sponge biofilms greatly favor retaining comammox Nitrospira in wastewater treatment and highlights an essential role of biomass retention in the comammox prevalence. Moreover, analyses of the assembled metagenomic sequences revealed that the retrieved amoA gene sequences affiliated with comammox Nitrospira (53.9-66.0% read counts of total amoA gene reads) were always higher than those (28.4-43.4%) related to ß-proteobacterial AOB taxa. The comammox Nitrospira bacteria detected in the present biofilm systems were close to clade A Candidatus Nitrospira nitrosa.

Laboratory Investigation of Carbon Black/Bio-Oil Composite Modified Asphalt.

As environmentally friendly materials, carbon black and bio-oil can be used as modifiers to effectively enhance the poor high-temperature and low-temperature performance of base asphalt and its mixture. Different carbon black and bio-oil contents and shear time were selected as the test influencing factors in this work. Based on the Box-Behnken design (BBD), carbon black/bio-oil composite modified asphalt was prepared to perform the softening point, penetration, multiple stress creep and recovery (MSCR), and bending beam rheometer (BBR) tests. The response surface method (RSM) was used to analyze the test results. In addition, the base asphalt mixtures and the optimal performance carbon black/bio-oil composite modified asphalt mixtures were formed for rutting and low-temperature splitting tests. The results show that incorporating carbon black can enhance the asphalt's high-temperature performance by the test results of irrecoverable creep compliance (Jnr) and strain recovery rate (R). By contrast, the stiffness modulus (S) and creep rate (M) test results show that bio-oil can enhance the asphalt's low-temperature performance. The quadratic function models between the performance indicators of carbon black/bio-oil composite modified asphalt and the test influencing factors were established based on the RSM. The optimal performance modified asphalt mixture's carbon black and bio-oil content was 15.05% and 9.631%, and the shear time was 62.667 min. It was revealed that the high-temperature stability and low-temperature crack resistance of the carbon black/bio-oil composite modified asphalt mixture were better than that of the base asphalt mixture because of its higher dynamic stability (DS) and toughness. Therefore, carbon black/bio-oil composite modified asphalt mixture can be used as a new type of choice for road construction materials, which is in line with green development.

Study on Properties of Bone Glue/Polyurethane Composite Modified Asphalt and Its Mixture.

Composite modification technology is widely used in the materials field. To enhance the property of polyurethane modified asphalt and realize its application in road engineering, the bone glue/polyurethane composite modified asphalt (CMA) was prepared using bone glue, polyurethane, and neat asphalt in this research. The bone glue content ranges 5-10%, that of the polyurethane is 1-5%. The relationship between the modifier's content and the conventional properties and rheological properties of CMA was revealed by response surface methodology (RSM). The CMA performance was further verified under the optimal content of the bone glue and polyurethane. The differences of properties of styrene-butadienestyrene (SBS) modified asphalt mixture, neat asphalt mixture, and bone glue/polyurethane CMA mixture were compared and analyzed by using the pavement performance test. The results showed that the CMA's conventional properties and rheological properties are improved. The optimal bone glue content and polyurethane content determined by RSM are 6.848% and 2.759%, respectively. The low-temperature crack resistance and water stability of the CMA mixture are enhanced, better than neat asphalt mixture and SBS modified asphalt mixture. The CMA mixture's dynamic stability is 85% of SBS modified asphalt mixture, but it is 2.4 times of neat asphalt mixture. The result indicated that the bone glue/polyurethane CMA mixture still has certain advantages of high-temperature stability. In this research, the composite modification of bone glue and polyurethane can significantly enhance the characteristic of asphalt and asphalt mixture and provide a new method for applying and promoting polyurethane modified asphalt in road engineering.

The lncRNA ANRIL regulates endothelial dysfunction by targeting the let-7b/TGF-ßR1 signalling pathway.

The long noncoding RNA antisense noncoding RNA in the INK4 locus (ANRIL) plays a critical role in the development of atherosclerosis. However, the precise effect of ANRIL on endothelial dysfunction remains unclear. In this study, we investigated ANRIL expression in patients with coronary artery disease and elucidated the molecular mechanism underlying its effect. ANRIL expression was detected in the blood plasma of 111 patients. We analysed the correlation between ANRIL and endothelial dysfunction markers. We also examined the effect of ANRIL on the regulation of endothelial dysfunction. ANRIL levels were increased in patients with acute coronary syndrome. The expression of ANRIL is associated with the inflammatory cytokines monocyte chemoattractant protein-1 and interleukin-10, which are secreted in response to endothelial dysfunction. Knockdown of ANRIL significantly promoted cell proliferation and tubule formation and inhibited inflammatory activation and apoptosis of human umbilical vein endothelial cells (HUVEC). ANRIL-mediated inhibition of let-7b regulates HUVEC dysfunction by targeting the TGF-ßR1/Smad signalling pathway. This study highlights a new therapeutic strategy for preventing endothelial dysfunction associated with cardiovascular disease.

Analysis on Three-Dimensional Strength Influencing Factors and Control Measures of Asphalt Mixtures.

Strength is an important parameter for the design of asphalt pavement materials and structures. To study the influence of various factors on the three-dimensional strength of asphalt mixtures, three aggregate gradations (dense-graded bituminous mixture AC-13, stone mastic asphalt SMA-13 and bituminous stabilization aggregate paving mixture OGFC-13) and two binders (SBS modified bitumen and 70# base bitumen) were used to prepare the asphalt mixture specimens. Among them, SBS+SMA-13 asphalt mixture has the best performance. On this basis, the uniaxial compressive test, uniaxial tensile test and confining triaxial test were conducted on the SBS+SMA-13 asphalt mixture under six oil-stone ratios conditions (5.5%, 5.7%, 5.9%, 6.1%, 6.3%, and 6.5%), six temperatures conditions (5 °C, 10 °C, 15 °C, 20 °C, 25 °C, and 30 °C), and five loading rates conditions (1 mm/min, 2 mm/min, 3 mm/min, 4 mm/min, and 5 mm/min). In addition, a unified three-dimensional strength calculation model considering the influence of temperature, loading rate, and oil-stone ratio was proposed, and the change law of the three-dimensional strength with these above factors was revealed. Furthermore, two sets of three-factor three-level orthogonal tests were carried out on the SMA-13 asphalt mixture. The sensitivity analysis and strength regulation research between three-dimensional strength and each factor were carried out. The results show that the type of asphalt has the greatest influence on the strength of the mixture, the temperature has the second most influence, the loading rate has less influence, and the oil-stone ratio has the least influence. The strength regulations proposed to improve the strength of the asphalt mixture include the use of modified asphalt, high-temperature stability high-quality asphalt, and the lower oil-stone ratio than the Marshall optimal oil-stone ratio. The strength control measures proposed from the perspective of the three-dimensional stress state, the joint failure of each stress components and real stress states are taken into consideration.

Degradation of Carbendazim in Soil: Effect of Sewage Sludge-Derived Biochars.

Application of biochar in soils can affect the soil properties and, in turn, the fate of pesticides. Batch experiments were conducted to investigate the effect of sewage sludge-derived biochars on the dissipation of a fungicide carbendazim in soil, and the transformation of carbendazim in soil was also studied. Results showed that the dissipation of carbendazim was fastest in a loamy soil SD with a half-life of 11.0 d among the three kinds of soils tested in this study. A dual effect (both acceleration and inhibition) of sewage sludge-derived biochars on carbendazim degradation in soil was reported. The addition of 10% biochars produced at 700 °C (BC 700) in soil could accelerate the carbendazim degradation, but an inhibitory effect was observed for 10% BC 300 or BC 500. Degradation of carbendazim was significantly inhibited when 0.5 or 5% BC 700 was added in soil but accelerated when the amendment ratio of BC 700 was increased to 10%. Such complex effects of the sewage sludge biochar should be taken into consideration in risk assessment of pesticides and the biochar effects on soil remediation. Eight metabolites of carbendazim were characterized, seven of which were reported in unamended soil for the first time. The metabolic pathways of carbendazim in soil are proposed.

Nonlinear Fatigue Damage Model of Asphalt Mixture Based on Dynamic Modulus and Residual Strength Decay.

In order to describe the fatigue damage state of asphalt mixture more reasonably, direct tensile tests of the fatigue and the residual strength under stress levels of 1.00 MPa, 0.50 MPa and 0.25 MPa with five parallel tests were carried out. The trabecular specimens of AC-13C asphalt mixture (25 cm × 5 cm × 5 cm) were manufactured with Styrene-Butadiene-Styrene (SBS) modified asphalt, aggregate basalt and limestone mineral filler. The optimum asphalt-aggregate ratio was 5.2%. The dynamic modulus decay and the residual strength decay were termed as the damage variables to evaluate the fatigue damage process of asphalt mixtures, respectively. Based on the test results, the decay patterns of the dynamic modulus and the residual strength during fatigue tests under different stress states were revealed, and the model and the parameters of fatigue damage according to the corresponding decay patterns were obtained. Then, based on the assumption that the residual strength and dynamic modulus depend on the same damage state, the relationship between the two damage definitions was given, and the residual strength-dynamic modulus coupled model was established. The results showed that the residual strength-dynamic modulus coupled model could better describe the fatigue damage evolution law of asphalt mixture, and the parameter of this coupled model could be obtained by less residual strength tests. A modified formula for calculating the damage variables associated with residual strength and dynamic modulus was proposed based on the relationship between two kinds of damage variables.

Adsorption-desorption behavior of carbendazim by sewage sludge-derived biochar and its possible mechanism.

Biochar application in agricultural soil for environmental remediation has received increasing attention, however, few studies are focused on sewage sludge based biochar. The present study evaluated the effect of raw sewage sludge and sewage sludge based biochars produced at different pyrolysis temperatures (100-700 °C) on the adsorption-desorption of carbendazim in soil. Sewage sludge derived biochar significantly enhanced the sorption affinity and limited the desorption capacity of the soil for carbendazim. A maximum removal efficiency of 98.9% and a greatest value of 144.05 ± 0.32 µg g-1 sorption capacity occurred in soil amended with biochar pyrolyzed at 700 °C (BC700). As the pyrolysis temperature and the amendment rate of biochars increased, the sorption of carbendazim was promoted and desorption was further inhibited. The adsorption-desorption hysteresis index of carbendazim was consistently higher in soils amended with biochars (>0.85) than in the unamended soil (0.42-0.68), implying that carbendazim could be immobilized in soil amended with sewage sludge derived biochars. The partition effect was dominant in the sorption process for carbendazim in the biochar-soil mixtures. This study will be helpful for the disposal of sewage sludge and its utilization, and it is the first report for the study the sorption-desorption process of carbendazim in soil amended with sewage sludge derived biochar. Furthermore, these findings may be also useful for understanding the distribution and transport of carbendazim in the environment and will be of great significance in remediation strategies for contaminated soil.

Influence of Soil Factors on the Stereoselective Fate of a Novel Chiral Insecticide, Paichongding, in Flooded Paddy Soils.

In this study, the fate of paichongding was investigated in three soils with contrasting soil properties. In general, low soil pH has the potential to retard the mineralization and promote the dissipation of paichongding and the formation of its primary transformation product and to accelerate the formation of bound residue. The dissipation of paichongding stereoisomers was very fast and diastereoselective. This selectivity was found only between diastereomers and not between enantiomers and was observed to be soil dependent. In the acidic soil, the enantiomers (5R,7R)- and (5S,7S)-paichongding were degraded more quickly than (5R,7S)- and (5S,7R)-paichongding, whereas a contrary trend was observed in the neutral soil, and such selectivity did not occur in the alkaline soil. The OM and clay contents also played important roles in the fate of paichongding. This effect of soil properties should be considered in risk assessment of chiral pesticides and their application in the field.

Synthesis and characterization of polyamidoamine dendrimer-coated multi-walled carbon nanotubes and their application in gene delivery systems.

With the aim of improving the amount and delivery efficiency of genes taken by carbon nanotubes into human cancer cells, different generations of polyamidoamine dendrimer modified multi-walled carbon nanotubes (dMNTs) were fabricated, and characterized by high-resolution transmission electron microscopy, atomic force microscopy, x-ray photoelectron spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis, revealing the presence of dendrimer capped on the surface of carbon nanotubes. The dMNTs fully conjugated with FITC-labeled antisense c-myc oligonucleotides (asODN), those resultant asODN-dMNTs composites were incubated with human breast cancer cell line MCF-7 cells and MDA-MB-435 cells, and liver cancer cell line HepG2 cells, and confirmed to enter into tumor cells within 15 min by laser confocal microscopy. These composites inhibited the cell growth in time- and dose-dependent means, and down-regulated the expression of the c-myc gene and C-Myc protein. Compared with the composites of CNT-NH(2)-asODN and dendrimer-asODN, no. 5 generation of dendrimer-modified MNT-asODN composites exhibit maximal transfection efficiencies and inhibition effects on tumor cells. The intracellular gene transport and uptake via dMNTs should be generic for the mammalian cell lines. The dMNTs have potentials in applications such as gene or drug delivery for cancer therapy and molecular imaging.

Dendrimer-modified magnetic nanoparticles enhance efficiency of gene delivery system.

Magnetic nanoparticles (MNP) with a diameter of 8 nm were modified with different generations of polyamidoamine (PAMAM) dendrimers and mixed with antisense survivin oligodeoxynucleotide (asODN). The MNP then formed asODN-dendrimer-MNP composites, which we incubated with human tumor cell lines such as human breast cancer MCF-7, MDA-MB-435, and liver cancer HepG2 and then analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, quantitative reverse transcription-PCR, Western blotting, laser confocal microscopy, and high-resolution transmission electron microscopy. Results showed that the asODN-dendrimer-MNP composites were successfully synthesized, can enter into tumor cells within 15 min, caused marked down-regulation of the survivin gene and protein, and inhibited cell growth in dose- and time-dependent means. No.5 generation of asODN-dendrimer-MNP composites exhibits the highest efficiency for cellular transfection and inhibition. These results show that PAMAM dendrimer-modified MNPs may be a good gene delivery system and have potential applications in cancer therapy and molecular imaging diagnosis.