Objective To determine whether lymph node-targeted chemotherapy with carbon nanoparticles absorbing 5-FU affects expressions of bcl-2, bax and caspase-3 in gastric cancer tissues, metastatic lymph nodes and normal gastric mucosa. Methods Twenty-eight patients with gastric cancer in our department were divided into lymph node-targeted chemotherapy (LNTC) group and control group from October 2005 to August 2006. The patients were treated with carbon nanoparticles absorbing 5-FU before operation in LNTC group and those were operated directly in control group. The gastric cancer tissues, metastatic lymph nodes and normal gastric mucosa were collected after operation. The expressions of bcl-2, bax and caspase-3 in those tissues were determined by immunohistochemical technique. Results In LNTC group, the positive expression rate of bcl-2 in gastric cancer tissues and metastatic lymph nodes was significantly lower than those in control group (28.6% vs . 78.6% , 25.0% vs . 70.0% , P ＜ 0.05), the positive expression rate of bax (85.7% vs . 28.6% , 80.0% vs . 30.0% ) and caspase-3 (57.1% vs . 14.3% , 55.0% vs . 15.0% ) in gastric cancer tissues and metastatic lymph nodes was significantly higher than those in control group ( P ＜ 0.05). The positive expression rate of bcl-2, bax and caspase-3 in normal gastric mucosa was not significantly different between two groups ( P ＞ 0.05). Conclusion The lymph node-targeted chemotherapy with carbon nanoparticles absorbing 5-FU can down-regulate the expression of bcl-2 and up-regulate the expression of bax and caspase-3 in gastric cancer tissues and metastatic lymph nodes, and therefore by affecting the expression levels of these apoptosis molecules may be one of the ways to induce tumor cell apoptosis.
As drug carriers, magnetic nanoparticles can specifically bind to tumors and have the potential for targeted therapy. It is of great significance to explore non-invasive imaging methods that can detect the distribution of magnetic nanoparticles. Based on the mechanism that magnetic nanoparticles can generate ultrasonic waves through the pulsed magnetic field excitation, the sound pressure wave equation containing the concentration information of magnetic nanoparticles was derived. Using the finite element method and the analytical solution, the consistent transient pulsed magnetic field was obtained. A three-dimensional simulation model was constructed for the coupling calculation of electromagnetic field and sound field. The simulation results verified that the sound pressure waveform at the detection point reflected the position of magnetic nanoparticles in biological tissue. Using the sound pressure data detected by the ultrasonic transducer, the B-scan imaging of the magnetic nanoparticles was achieved. The maximum error of the target area position was 1.56%, and the magnetic nanoparticles regions with different concentrations were distinguished by comparing the amplitude of the boundary signals in the image. Studies in this paper indicate that B-scan imaging can quickly and accurately obtain the dimensional and positional information of the target region and is expected to be used for the detection of magnetic nanoparticles in targeted therapy.
This paper provides a brief overview of the current research activities which focused on the bio-application of gold magnetic nanocomposite particles. By combining the magnetic characteristics of the iron oxide core with the unique features of nano-gold particles such as targeting by surface modification and optical properties, such composite nanoparticles have a wide range of applications in cancer hyperthermia, CT and MRI imaging, bio-separation, biosensors, gene diagnosis, drug targeting and many other biomedical fields.
Objective To assess the applied significance of carbon nanoparticles in central compartment lymph node dissection in treatment of cN0 papillary thyroid carcinoma. Methods Sixty-eight patients with cN0 papillary thyroid carcinoma who were treated in Tongji Hospital of Tongji Medical College from May. to Oct. in 2012 were randomly allocated to the control group （n=32） and the carbon nanoparticles trace group （tracer group， n=36）， receiving non-carbon nanoparticles trace and carbon nanoparticles trace respectively. All patients were received total resection of thyroid plus the affected side and （or） contralateral side central compartment lymph node dissection. The lymph node-related indexes（including number of dissected lymph node at Ⅵarea and lymph node metastasis rate at Ⅵarea） and operative indexs （including operation time， blood loss， drainage time， complication， and hospital stay） were collected and compared between the 2 groups. Results There were 205 and 324 dissected lymph node at central compartment in control group and tracer group respectively. The results of postoperative pathology showed that the number of lymph node in central compartment of the tracer group was much more than those of control group （8.99±2.24 vs. 6.41±1.56， P＜0.001）. The metastasis rate of central compartment lymph node were 40.6% （13/32） in control group and 47.2% （17/36） in tracer group， but there was no significant difference between the 2 groups （P=0.762）. But in medial area of laryngeal recurrent nerve， the metastasis rate in the tracer group （38.9%， 14/36） was much higher than those of control group （12.5%， 4/32）， P=0.029. There were no significant differences in the operation time， blood loss， drainage time， hospital stay， and complication incidence such as bleeding， temporary hypocalcemia， and injury of superior laryngeal nerve between 2 groups （P＞0.05）. All the patients in 2 groups had followed-up for 6 months without death， recurrence， and metastasis.Conclusions The lymphatic tracer technique of carbon nanoparticles may improve the number of dissected lymph nodes in central region of cN0 papillary thyroid carcinoma， without increasing （or prolonging） operation time， intraoperative blood loss， and postoperative hospital stay， and can accurately represent the metastasis of lymph node， thus to make the staging of the tumor accurately and guide postoperative treatment.
Multidrug resistance (MDR) remains the major obstacle to the success of clinical cancer chemotherapy. P-glycoprotein (P-gp), encoded by the MDR1, is an important part with complex mechanisms associated with the MDR. In order to overcome the MDR of tumors, we in the present experimental design incorporated small interfering RNA (siRNA) targeting MDR1 gene and anticancer drug paclitaxel (PTX) into the solid lipid nanoparticles (SLNs) to achieve the combinational therapeutic effects of genetherapy and chemotherapy. In this study, siRNA-PTX-SLNs were successfully prepared. The cytotoxicity of blank SLNs and siRNA-PTX-SLNs in MCF-7 cells and MCF-7/ADR cells were detected by MTT; and the uptake efficiency of PTX in MCF-7/ADR cells were detected via HPLC method; quantitative real-time PCR and flow cytometry were performed to investigate the silencing effect of siRNA-PTX-SLNs on MDR1 gene in MCF-7/ADR cells. The results showed that PTX loaded SLNs could significantly inhibit the growth of tumor cells, and more importantly, the MDR tumor cells treated with siRNA-PTX-SLNs showed the lowest viability. HPLC study showed that SLNs could enhance the cellular uptake for PTX. Meanwhile, siRNA delivered by SLNs significantly decreased the P-gp expression in MDR tumor cells, thus increased the cellular accumulation of rhodamine123 as a P-gp substrate. In conclusion, the MDR1 gene could be silenced by siRNA-PTX-SLNs, which could promote the growth inhibition efficiency of PTX on tumor cells, leading to synergetic effect on MDR tumor therapy.
Objective To observe the inhibitory characteristics of silver nanoparticles (AgNP) on bacterial biofilms and investigate their inhibitory effect on biofilm formation on three common orthopedic biomaterials. Methods The minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC) of AgNP were determined by microplate dilution assay. Biofilms of Staphylococcus aureus (ATCC 25923) were cultured on three orthopedic biomaterials (titanium alloy, titanium oxide, and stainless steel) and intervened with AgNP at concentrations of 32, 16, 8, 4, 2 and 0 μg/mL to determine the MBICs on the three materials. The effects of AgNP on biofilm formation were analyzed by scanning electron microscopy and measuring optical density. Results The MIC and MBIC of AgNP in the microplate assay were both 16 μg/mL. The MBICs of AgNP on biofilm formation in titanium oxide, titanium alloy, and stainless steel were 16 μg/mL, 32 μg/mL, and 32 μg/mL, respectively. Among the three materials, the lowest optical density was observed on titanium oxide, while the highest was on titanium alloy. Conclusions AgNP has strong antibacterial biofilm characteristics and can prevent the formation of Staphylococcus aureus biofilm in vitro. Biofilm formation is most pronounced on titanium alloy, least on titanium oxide, and intermediate on stainless steel.
Objective To investigate the effect of solid lipid nanoparticles (SLNs) on enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro by resveratrol (Res), and provide a method for the treatment of bone homeostasis disorders. MethodsRes-SLNs were prepared by high-temperature emulsification and low-temperature solidification method, and then the 2nd-3rd generation BMSCs from Sprague Dawley rat were co-cultured with different concentrations (0, 0.1, 1, 5, 10, 20 μmol/L) of Res and Res-SLNs. The effects of Res and Res-SLNs on the cell viability of BMSCs were detected by cell counting kit 8 (CCK-8) and live/dead cell staining; the effects of Res and Res-SLNs on the osteogenic differentiation of BMSCs were detected by alkaline phosphatase (ALP) staining and alizarin red S (ARS) staining after osteogenic differentiation induction, and the optimal concentration of Res-SLNs for gene detection was determined. Anti-osteocalcin (OCN) immunofluorescence staining and real-time fluorescent quantitative PCR (RT-qPCR) were used to detect the effect of Res and Res-SLNs on osteoblast-related genes (ALP and OCN) of BMSCs. ResultsLive/dead cell staining showed that there was no significant difference in the number of dead cells between Res and Res-SLNs groups; CCK-8 detection showed that the activity of BMSCs in Res group was significantly reduced at the concentration of 20 μmol/L (P<0.05), while Res-SLNs activity was not affected by Res concentration (P>0.05). After osteogenic differentiation, the staining intensity of ALP and ARS in both groups was dose-dependent. The percentage of ALP positive staining area and the percentage of mineralized nodule area in Res group and Res-SLNs group reached the maximum at the concentrations of 10 μmol/L and 1 μmol/L, respectively (P<0.05), and then decreased gradually; the most effective concentration of Res-SLNs was 1 μmol/L. The expression of OCN and the relative expression of ALP and OCN mRNA in Res-SLNs group were significantly higher than those in Res group (P<0.05). ConclusionEncapsulation of SLNs can improve the effect of Res on promoting osteogenesis, and achieve the best effect of osteogenic differentiation of BMSCs at a lower concentration, which is expected to be used in the treatment of bone homeostasis imbalance diseases.
The study of viruses traditionally focused on their roles as infectious agents and as tools for understanding cell biology. Recently, however, with the development of structural biology, viruses have now been receiving particular attention in nanotechnology. By chemical methods or by gene modification, viruses have been functionalized as potential building blocks for several applications, such as drug/gene delivery vehicles, advanced vaccine vehicles, and special inorganic or organic nanomaterials. Here we highlight some of the recent progresses in the medical applications of viruses.
Objective To investigate an inhibitive effect of the chitosan nanoparticles with the proliferation cell nuclear antigen （PCNA）-antisense oligo deoxy nucleotides (ASODN) on the intimal cell proliferation after the vein grafting.Methods Fiftyfour male SD rats, weighing 450-600g, were randomly divided in the experimental group and the control group of 27 rats each. In the experimental group, the chitosan nanoparticles with PCNAASODN were infused into the anastomosis segment of the right jugular artery and vein; then, the anastomosis segment was transplanted to the jugular artery on the same side. The rats in the control group were infused with normal saline by the same procedures. There were 24 rats in each group which used to experiment. The hemodynamic data were obtained from the Doppler ultrasound examinations at 1, 2, 3 and 4 weeks. The specimens were taken. Immunohistochemistry, Westernblot, and bloodvesselwall histopathology were performed at the different week points. Results There was no significant difference in the thrombogenesis rate between the experimental group and the control group (3/27 vs. 3/27,P＞0.05). During the 4 week observation, PCNA Westernblot showed that the PCNA level was lower in the grafted vein and the anastomosis segment in the experimental group than in the control group. The indexes of the PCNA postive proliferating cells in the intimal area (0.13%±0.11%，0.79%±0.28%，0.45%±0.29%, 0.43%±0.25%) and the medial area (1.90%± 0.84%，2.11%±0.98%，2.48%±0.77%，2.17%±0.36%) were significantlydecreased at 1,2,3 and 4 weeks in the experimental group when compared with those in the control group（P＜0.05）. The lumen areas in the grafted vein (88.71±16.96，95.98±21.44，88.48±32.81，97.86±34.11 μm 2) and the anastomosis segment (41.49±3.34，45.15±11.65，46.27±8.90，51.62±8.85 μm 2) were significantly greater in the experimental group than in the control group (P＜0.05). The ratios of the initmal area to the medial area in the grafted vein (22.73%±3.11%，32.40%±4.55%，45.14%±3.19%，45.70%±5.01%) and the anastomsis segment (41.49%±3.34%，45.15%±11.65%，46.27%±890%，51.62%±8.85%) were significantly smaller in the experimental group than in the control group（P＜0.05）. The maximum velocities (Vmax) of the blood flow inthe grafted vein and the anastomsis segment were almost the same in the two groups at 1 week, but had different changes at the next 3 weekpoints. In the control group, the Vmax of the blood flow gradually increased and at 3 weeks it reached the peak point; however, at 4 weeks it decreased. In the experimental group,the Vmax of the blood flow gradually decreased, and at 3 weeks it decreased to the lowest point; however, at 4 weeks it increased. So, at 4 weeks the Vmax of the blood flow in the grafted vein and the anastomsis segment was almost the samein the two groups. There was no significant difference in the Vmax of the bloodflow between the two groups (P＞0.05), but in the same group there wasa significant difference at the different time points. Conclusion The chitosan nanoparticles with PCNAASODN can effectively inhibit the intimal cell proliferation after the grafting of the blood vessel, so that the neointimal thickening can be prevented.
ObjectiveTo investigate effect of carbon nanoparticles on number of lymph nodes harvested in radical operation of rectal cancer after neoadjuvant chemoradiotherapy. MethodsOne hundred and five patients diagnosed with low and middle rectal cancer and received radical operation after neoadjuvant chemoradiotherapy in Cancer Hospital, Chinese Academy of Medical Sciences from March 1, 2014 to October 31, 2015 were included. Thirtysix patients were injected with carbon nanoparticles by colonoscopy before surgery and were classified as study group, and the rest patients were classified as control group. According to the same principle of surgery and procedure of pathological specimen handling, the effect of carbon nanoparticles on lymph node harvested in resected specimens was analyzed. ResultsThe total lymph nodes harvested were 764 in the study group and 1 242 in the control group. Among them, the metastatic lymph nodes were 19 in the study group, 58 in the control group. Although the average lymph nodes harvested in each patient had no significant difference between the study group and the control group (21.22±7.13 versus 18.00±9.84, t=1.739, P=0.085), the proportion of patients with 12 or more than 12 lymph nodes harvested in the study group was significantly higher than that in the control group [88.9% (32/36) versus 71.0% (49/69), χ2=4.287, P=0.038]. The ratio of patients with metastatic lymph nodes [27.8% (10/36) versus 33.3% (23/69), χ2=0.339, P=0.561] and the average metastatic lymph nodes harvested in each patient (1.90±1.29 versus 2.52±2.33, t=0.788, P=0.437) all had no significant differences between the study group and the control group. ConclusionThe injection of carbon nanoparticles by colonoscopy before surgery could increase detection rate of 12 or more than 12 lymph nodes in resected specimens of patients who were diagnosed with low and middle rectal cancer and received radical operation after neoadjuvant chemoradiotherapy.