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.
ObjectiveTo investigate the applicated value of carbon nanoparticle lymphatic tracer in laparoscopic assisted radical gastrectomy for advanced gastric cancer. MethodsForty-two patients with advanced gastric cancer who were admitted to the Department of General Surgery in The Affiliated Cancer Hospital of Zhengzhou University from March to September in 2014, were collected prospectively and randomly divided into two groups (carbon nanoparticle group and control group), each group enrolled in 21 cases. After improving relevant auxiliary inspection, subserosal injection of carbon nanoparticle around the tumor was performed via venous infusion needle laparoscopically at the beginning of surgery in carbon nanoparticle group, while the patients routinely underwent laparoscopic assisted radical gastrectomy in control group. Comparison of the results of harvested lymph nodes and its detection time between the two groups was performed, and the perioperative complications were also evaluated. ResultsA total of 678 lymph nodes were detected in carbon nanoparticle group and 447 lymph nodes were detected in control group. The number of harvested lymph nodes in carbon nanoparticle group (32.28±4.10) was significantly higher than that of control group (21.28±2.74), P < 0.05. The mean harvest time in carbon nanoparticle group was shorter than that of control group[(24.09± 3.58) min vs. (32.76±4.76) min, P < 0.05]. The proportion of harvested small lymph node (≤5 mm) in carbon nanoparticle group was higher than that of control group[71.68% (486/678) vs. 48.99% (219/447), P < 0.01]. The number of black-dyed harvested lymph node was 506 (74.63%) and the metastasis rate of black-dyed lymph node was 26.28% (133/506) in carbon nanoparticle group, that the metastasis rate of black-dyed lymph node group was significantly higher than those of without black-dyed lymph node group[6.40% (11/172)] and control group[19.24% (86/447)], P < 0.05. No serious side effect caused by carbon nanoparticle was observed. ConclusionsThe application of diluted carbon nanoparticle lymphatic tracer has a good effect in the dissection of lymph nodes in laparoscopic assisted radical gastrectomy for advanced gastric cancer. It improves the detection rate of lymph nodes, especially the small lymph nodes, and it is safe and feasible.
ObjectiveTo explore the application value of carbon nanoparticles during radical operation of differentiated thyroid cancer (DTC).MethodsThe DTC patients underwent total thyroidectomy plus neck lymph node (area Ⅳ) dissection from September 2017 to September 2019 in this hospital were retrospectively collected, who were divided into observation group and control group according to using carbon nanoparticles or not during the operation. The operation related informations [operation time, intraoperative blood loss, total drainage volume on day 3 after operation, postoperative hospitalization time, number of lymph nodes dissection (area Ⅳ), lymph node metastasis rate, and rate of parathyroid glands resected by mistake during operation] and blood calcium (Ca2+) level and parathyroid hormone (PTH) level before and after (24 h and 1 month) operation were compared between the two groups.ResultsA total of 134 patients with DTC were collected, including 76 patients in the observation group and 58 patients in the control group. There were no significant differences in baseline data such as gender, age, etc. between the two groups (P>0.05). Although there were no significant differences in terms of operation time, intraoperative blood loss, total drainage volume on day 3 after operation, postoperative hospitalization time, lymph node metastasis rate between the two groups (P>0.05), the numbers of lymph node dissection and metastasis (area Ⅳ) were more and rate of parathyroid glands resected by mistake during operation was lower in the observation group as compared with the control group (P<0.05). On hour 24 after operation, the levels of Ca2+ and PTH in the observation group were higher than those in the control group (P<0.05). On month 1 after operation, the PTH level in the observation group was still higher than that in the control group (P<0.05), but there was no significant difference in Ca2+ level between the two groups (P>0.05). ConclusionCarbon nanoparticles can better protect the function of parathyroid gland during radical operation of DTC and clean neck lymph nodes more thoroughly.
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.
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.
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.
Objective To explore the effect of carbon nanoparticles dyeing on axillary lymph node dissection in modified radical mastectomy for breast cancer. Methods Eighty-eight patients with breast cancer who received modified radical mastectomy in Mianyang Central Hospital between Mar. 2012 and May. 2013 were recruited in the study, and they were equally divided into areola group and peripheral tumor group. After induction of anesthesia before operation, carbon nanoparticles were injected around the areolar in the areola group, and carbon nanoparticles were injected around the tumor in the peripheral tumor group. The number of dissected lymph nodes(be dyed or not be dyed), metastatic lymph nodes, and black dyed lymph nodes, as well as value of operation related indexes were recorded and compared. Results In the areola group, lymph nodes were detected in 1 453, in which 1 396 lymph nodes were stained black(96.1%); the average number of dissected lymph nodes were 33.0±7.1 per case; and 19 patients (43.2%, in total of 220 metastatic lymph nodes) of them were suffered from lymph node metastasis with the average number of metastatic lymph nodes of 5±2 per case. in addition, in the areola group, operative time were(122.1±10.2) min, blood loss were(83.8±10.1) mL, postoperative hospital stay were(7±1) d, and postoperative complications occurred in 3 patients. In the peripheral tumor group, lymph nodes were detected in 909, in which 594 lymph nodes were stained black (65.3%); the average number of dissected lymph nodes were 20.7±3.2 per case; 20 patients (45.5%, in total of 88 metastatic lymph nodes) of them were suffered from lymph nodes metastasis, with the average number of metastatic lymph nodes of 2±1 per case. In addition, in the peripheral tumor group, operative time were (121.6±11.4) min, blood loss were (84.2±11.3) mL, postoperative hospital stay were (7±2) d, postoperative complications occurred in 3 patients. The black staining rate of lymph nodes, the number of lymph nodes retrieved, and the number of metastatic lymph nodes in areola group were significantly higher than those of peripheral tumor group(P < 0.01). Operative time, blood loss, postoperative hospital stay, and postoperative complication rate did not significantly differ between the 2 groups (P > 0.05). Conclusion The dyeing effect of carbon nanoparticles suspension, which was injected at areola area after induction of anesthesia, is better than that of injected around the tumor, without increasing the incidence of complication.
Objective To investigate the expression of caspase-3 in xenograft that was treated with targeted therapy with magnetic nanoparticles in nude mice. Methods QBC939 cell lines were injected into nude mice subcutaneously to establish the model of human cholangiocarcinoma xenograft. After two weeks of tumor inoculation, the animal models were divided randomly into 4 groups: group A received placebo (sodium chloride), group B were treated with magnetic nanoparticles (250 mg/kg), group C were treated with magnetic nanoparticles (150 mg /kg) combined with inner-stent, group D with magnetic nanoparticles (250 mg /kg) combined with inner-stent (the inner-stent was used to generate the magnetic targeting effect). The 21th day after treatment, expression of caspase-3 in tumor cells of each groups were measured with histochemical method and RT-PCR. Results The quantity of caspase-3 in tumor cells that were treated with magnetic nanoparticles (250 mg/kg) combined with inner-stent was the most (P＜0.05), and the quantity of caspase-3 in cells of group C was significantly more than that of the other two groups (P＜0.05). While the quantity of caspase-3 in group B was more than that of the control group(P＜0.05). Conclusion The use of magnetic nanoparticles combined with inner-stent may increase the expression of caspase-3, and the expression is dose-dependent with magnetic nanoparticles.
Objective To explore the diagnostic value of circulating tumor cells (CTC) measured by magnetic nanoparticle method in lung cancer. Methods (1) We measured binding capability of A549 or NCI-H1965 cell lines with recognition peptide and capture efficiency by adding tumor cells into the whole blood of healthy human. (2) We measured CTC of 34 patients suspected with lung cancer, and the counting results of CTC were compared with the following pathological results. Results (1) The binding capability was 80.0%±6.0% for A549 and 70.1%±4.8% for H1957, while the capture efficiency was 57.3%±7.0% for A549 and 37.3%±6.1% for H1975. (2) CTCs were identified in 71.9% of patients with lung cancer. The specificity was 83.3%, and area under receiver operating characteristic (ROC) curve was 0.792 (P=0.003). Conclusion CTC measured by magnetic nanoparticle method has promising application in the diagnosis of lung cancer.