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OBJECTIVE: The lactose-doxorubicin amphiphilic small molecule nanomicelles and evaluate its liver cancer targeting and antitumor efficacy and safety in vivo. METHODS: Lactose-doxorubicin nanomicelles (Lac-DOX NMs) were prepared by thin film hydration method. The particle size was determined by dynamic light scattering and observed by transmission electron microscopy. The effect of Lac-DOX NMs on the targeting of tumor cell was investigated by cell uptake experiments.Cytotoxicity of nanomicelles and free doxorubicin were evaluated by CCK-8 assay.The subcutaneous xenograft model of BALB/c-nu mice was constructed to investigate the anti-tumor effect of Lac-DOX NMs; the effect of the preparation on liver function of mice was examined by blood biochemical test to evaluate the safety of the preparation.RESULTS: Lac-DOX NMs were successfully prepared with a particle size of (169.2±0.9) nm. Cellular uptake experiments indicated that Lac-DOX NMs are targeted to HuH-7 hepatoma cells.The IC50 of nanomicelle and free DOX were 3.596 and 2.131 μg•mL-1, respectively. The results of pharmacodynamic experiments showed that Lac-DOX NMs could significantly inhibit the growth of transplanted tumors in mice. The tumor inhibition rates of high and low doses of Lac-DOX NMs were 69.72% and 52.40%, respectively, which were higher than those of free DOX (52.27%). P values are 0.000 16 and 0.94. CONCLUSION: Modification of doxorubicin with lactose and its preparation into nanometer preparations can significantly improve the targeting of doxorubicin to liver cancer cells, enhance the anti-tumor effect, reduce the side effects of doxorubicin, and improve the safety of medication.
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OBJECTIVE: To investigate a biomimetic nano-targeted drug modifide by cancer cell membrane and to discuss its efficiency in breast cancer. METHODS: The lac-DOX/DOX was prepared by filming-rehydration method, and the 4T1 cell membrane was extracted at the same time. The lac-DOX /DOX@4T1m was prepared by sonication method.. The morphology of lac-DOX /DOX@4T1m was observed by a transmission electron microscopy. The protein on 4T1 cell membrane was analyzed by gel electrophoresis. The targeting of drugs to homologous cancer cells in vivo and in vitro were evaluated by cell uptake experiments and imaging experiments of small animals. 4T1 tumor-bearing Balb/c mice were built, the anti-tumor efficacy and biosafety of lac-DOX/ DOX@4t1m were evaluated. RESULTS: The prepared lac-DOX /DOX@4T1m have a regular spherical shape with an average particle diameter of (204.8±13.0)nm, and the protein entirety remained on the cell membrane. The results of cell uptake experiments and in vivo imaging experiments of mice showed that lac-DOX/DOX@4T1m can target 4T1 cells. Antitumor test results showed that lac-DOX/ DOX@4T1m could inhibit tumor growth more effectively and significantly reduce the damage to liver function. CONCLUSION: In this study, a bionic nano-drug is successfully prepared, which improve the tumor targeting and therapeutic effect, reduce the toxic effects of adriamycin, and improve the drug safety.
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@#This study aimed to investigate the improvement of tolance and pharmacodynamics of nano-micelle irinotecan formulation compared with irinotecan hydrochloride injection(Campto). The toxic effects of the two formulations on colorectal cancer cells COLO205, HT-29, HCT-8 and SW480 were tested in vitro. COLO205 tumor-bearing mouse model was constructed. The two preparations were given via tail vein injection to investigate the maximum tolerance dose(MTD)of tumor-bearing mice to the two preparations, and then to explore the improvement of anti-tumor efficacy of nano-micelle irinotecan formulation near the MTD. The results showed that there was no significant difference in the inhibitory effect of the two formulations on the four colorectal cancer cells in vitro. The MTD of nano-micelle irinotecan formulation and Campto was 432. 0 and 276. 5 mg/m2 respectively. Both of the two formulations showed significant anti-tumor effect in vivo, and the relative tumor proliferation rate and tumor wet weight inhibition rate of nano-micelle irinotecan formulation at high dose(345. 6 mg/m2)were significantly better than those of Campto at two doses(177. 0 and 221. 2 mg/m2)(P< 0. 05).
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@#Hyaluronic acid, also called hyaluronan(HA)is a biocompatible and biodegradable linear polysaccharide which is of interest for tumor targeting through cell surface CD44 receptors. It is widely applied in the field of tumor therapy as an anticancer drug delivery carrier, and has become a hot spot in the research of tumor targeted drug delivery system. In tumor drug therapy, the key to reduce toxicity is to actively target tumors by using anatomical, pathophysiological and microenvironmental differences between malignant tumors and normal tissues. Differentiation cluster 44(CD44)is a high-affinity receptor for HA, which can be marked as a tumor marker or a targeting receptor because it is overexpressed in tumor cells. The overexpression of CD44 receptors was observed in many tumors such as breast cancer, colorectal cancer, liver cancer and pancreatic cancer. The effect of hyaluronic acid drug nanocarriers on various tumors is briefly described, indicating that the overexpression of CD44 receptor is an ideal choice for the treatment of hyaluronic acid-based drug carriers. The CD44 ligand can increase the affinity of the nanocarrier for tumor cells by binding to the nano drug carrier. The HA structure is known for its potent tumor targeting effect due to the inclusion of CD44 ligand, which enhances uptake of tumor cells by the HA-CD44 receptor-mediated endocytosis pathway. The study reviewed the progression of hyaluronic acid nanomicelles in clinical tumor therapy and its release behavior. The percentage of drug release and release rate are the key factors in the overall efficacy of the treatment strategy. Therefore, a great number of studies have focused on inducing drug release in Cytosol by taking advantage of the difference between the internal and external environments of nanostructured micelles or through external stimulation post-treatment applications. The study proved that an acid environment is more favorable to achieve a greater release and drugs can be quickly and completely released in an oxygen-deficient environment. In addition, the great potential of hyaluronic acid nanomicelles in tumor therapy was also further identified in this article. In vitro and in vivo experimental studies have repeatedly shown that hyaluronic acid-based nanomicelles are a drug- and gene-specific targeting tumor delivery method, in combination with passive targeting, this active targeting strategy is a promising approach to providing chemotherapy drugs to CD44 overexpressing tumors. In conclusion, hyaluronic acid-based nanomicelles are biologically safe with great potential to drug release, blood compatibility and systemic tumor targeting which all implied it has good application prospects in clinical tumor treatment.
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OBJECTIVE:To prepare the norcantharidin (NCTD) nano-micelle and study its antitumor effect. METHODS:NCTD nano-micelle was self-formed in water using Triblock copolymers distearyl phosphatidylethanolamine-polyethylene glycol-ma-leimide;its shape was observed,the drug-loading rate,entrapment efficiency,particle size,Zeta potential were investigated. MTT was used to investigate the cell survival rate of human lung cancer A549 cells in negative control group (Phosphate buffer solu-tion),carrier group (blank nano-micelle),positive control group (NCTD APIs,5-320 μg/mL) and NCTD nano-micelle group (NCTD,5-320 μg/mL) after acting different time (24,48,72 h). Tumor nude mice were randomly divided into blank control group,NCTD injection group(1 mg/kg),NCTD low-dose,high-dose groups(0.5,1 mg/kg),6 in each group. All mice were in-travenously injected relevant medicines in tail,once a day,for 8 weeks. Tumor size was measured every week,and tumor quality was detected after the second day of finishing administration. RESULTS:NCTD nano-micelle was round,drug-loading rate was (2.82±0.05)%,entrapment efficiency was(83.67±1.78)%,particle size was(138.6±45.8)nm,Zeta potential was -(12.75± 0.34)mV(n=6). Cell survival rate of A549 cells in carrier group had no obvious changes,and was obviously decreased in posi-tive control group and NCTD nano-micelle group,which was positively correlated with concentration and time. And the decrease degree of cell survival rate in NCTD nano-micelle group was stronger than positive control group(P<0.01). Compared with blank control group,the tumor quality of mice in 3 administration groups was reduced (P<0.05),the reduction degree in NCTD na-no-micelle high-dose group was stronger than NCTD nano-micelle injection group (P<0.05). CONCLUSIONS:NCTD nano-mi-celle is successfully prepared,which has good in vitro and in vitro anti-tumor effect on A549 cells.
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OBJECTIVE: To prepare puerarin-loaded PEG-PE nano-micelles and explore its tissue distribution in acute myocardial ischemia model mice. METHODS: Puerarin-loaded PEG-PE nano-micelles were prepared by thin-film hydration method. Sixty KM mice were randomly divided into two groups (30 in each group). Both were given puerarin-loaded PEG-PE nano-micelles at a dose of 20 mgkg-1. After 5 min of medication, the mice in one group were treated with ligation of coronary artery to establish acute myocardial ischemia, and the other one group was taken as the control. The animals were executed at 30, 60, 90, 120, 150 and 180 min, then the heart, liver, spleen, lung, and kidney were extracted. The content of puerarin in the organ tissue was determined by HPLC. RESULTS: The drug loading and drug encapsulation of puerarin-loaded PEG-PE nano-micelles were (5.8±1.3)% and (78.6±5.7)%, respectively, and the diameters and Zeta potential were 25 nm and -3 mV, respectively. The AUCs of tissue distribution of puerarin-loaded PEG-PE nano-micelles in the control group were in the sequence of liver>kidney>heart >spleen>lung>brain. While the AUCs of tissue distribution of PEGylated puerarin in acute myocardial ischemia model mice were in the sequence of liver≈heart>kidney>lung>spleen>brain. The AUCheart of puerarin-loaded PEG-PE nano-micelles in acute myocardial ischemia model mice was 1.9 times of that of the control mice (P<0.05). CONCLUSION: Puerarin-loaded PEG-PE nano-micelles show excellent drug loading capabilities. It has good heart-targeting property in early myocardial infarction area and can accumulate in the ischemic myocardium. This study provides important information for further development of prepamiceion.
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Salinomycin ,extensively used as an antibiotic in animal husbandry for a long time ,has recently been found to possess strong anti-cancer and anti-cancer stem cell efficacy ,as well as activities to overcome multi-drug resistance of tumor based on studies in vivo and in vitro in case reports in pilot clinical trials .Therefore ,salinomycin promised to be a novel anti-cancer agent .However ,the unfavorable property of poor aqueous solubility and the adverse effects of salinomycin were greatly hinder its clinical use .In order to improve its therapeutic index and alleviate its toxicity ,studies on nanotechnology-based deliv-ery systems of salinomycin had been widely conducted .In this article ,the latest development and application of salinomycin nanoformulations were reviewed .
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ABSTRACT:Objective To prepare polymeric nanomicelles capable of simultaneously loading doxorubicin (DOX) and Bcl‐2 small interfering RNA (Bcl‐2 siRNA ) , and to explore their in vitro cytotoxicity and cellular uptake in MCF‐7 human breast cancer cells .Methods Copolymer poly (ethylene glycol )‐g‐polyethylenimine‐g‐poly(γ‐benzyl‐L‐glutamate) was synthesized by the combination of reductive amination and carbodiimide methods , and its chemical structure was verified by 1 H NMR .Empty and drug‐loaded copolymeric nanomicelles were prepared by dialysis method and characterized by transmission electron microscope and dynamic light scattering .The ability of the nanomicelles to compress Bcl‐2 siRNA was measured by by agarose gel electrophoresis method . The release profiles of DOX and Bcl‐2 siRNA from the nanomicelles were explored by means of fluorescence spectrometry and dialysis method .The in vitro cytotoxicity and cellular uptake of DOX and Bcl‐2 siRNA co‐loaded nanomicelles in MCF‐7 human breast cancer cells were characterized by MTT assay and confocal laser scanning microscopy , respectively .Results The critical micelle concentration of the copolymer was about 4 mg/L ,and the sizes of self‐assembled empty and drug‐loaded nanomicelles were smaller than 200 nm .The drug‐loading efficiency and drug‐loading content of DOX in the nanomicelles were 88 .7% and 15 .1% ,respectively .The DOX‐loaded nanomicelles could efficiently compress Bcl‐2 siRNA when an N/P ratio was ≥64 .The zeta potential of DOX and Bcl‐2 siRNA co‐loaded nanomicelles was +30 mV .The release behavior of the cargoes from the nanomicells was pH‐sensitive , and the release of Bcl‐2 siRNA was more sensitive to acidic pH than that of DOX . The nanomicelles could simultaneously deliver DOX and Bcl‐2 siRNA into MCF‐7 cells , and the co‐delivered DOX and Bcl‐2 siRNA significantly increased the cytotoxicity of DOX (P<0 .05) .Conclusion The polymeric nanomicelles can co‐load DOX and Bcl‐2 siRNA and deliver them into MCF‐7 cells , and DOX in combination with Bcl‐2 siRNA can synergistically inhibit the growth of MCF‐7 cells and promote cell apoptosis ,suggesting that the nanomicells may be a promising carrier for the co‐delivery for chemotherapeutics and genes .