Breast cancer is the most common tumor in female, which seriously threatens the health of women. Triple-negative breast cancer is a subtype with the worst prognosis because of its special physiological characteristics and lack of targeted drugs. Therefore, it is urgent to develop new targeted treatments to improve the prognosis and survival rate of the patients. Previous studies have shown that heat shock protein gp96 is expressed on the membrane of a variety of cancer cells but not on the normal cells. Cell membrane gp96 levels are closely related to the poor prognosis of breast cancer, which may serve as a new target for breast cancer treatment. Based on the structure of gp96, we designed an α-helical peptide p37 that specifically targeting the ATP binding region of gp96. To improve the stability and decrease the degradation of the peptide, the N-terminus or C-terminus of p37 was coupled to PEG₂₀₀₀ or PEG₅₀₀₀ respectively, and four PEGylated polypeptides were obtained: mPEG₂₀₀₀CY, mPEG₅₀₀₀CY, mPEG₂₀₀₀LC, and mPEG₅₀₀₀LC. The PEGylated polypeptides inhibited the proliferation and invasion of breast cancer cell SK-BR-3, among which mPEG₂₀₀₀CY showed the most significant inhibitory effect. The half-life of mPEG₂₀₀₀CY in vivo was significantly longer than p37, and it effectively inhibited the growth of xenografted tumors of triple-negative breast cancer MDA-MB-231. The results provide a basis for the development of new targeted drugs against breast cancer, especially the triple-negative breast cancer.
Adenosine Triphosphate ; Female ; Heat-Shock Proteins ; Humans ; Peptides/pharmacology* ; Polyethylene Glycols ; Triple Negative Breast Neoplasms/pathology*

A novel oral delivery system that TPGS modified docetaxel proniosomes, DTX-TPGS-PN, was developed and the characterization after hydration was observed. Firstly, Doce-TPGS-PN was optimized by investing the factors, including the type of surfactant, methods of adding TPGS, content of TPGS and the molar ratio of span40/cholesterol, which may affecting the particle size, encapsulation efficiency and instantaneous release of drug in the formulation. Then, the morphology, particle size, Zeta potential, encapsulation efficiency and in vitro release of the formulation were evaluated. The result showed that hydrated nanoparticles of DTX-TPGS-PNs were (93 ± 6.5) nm in size,(-83.95 ± 3.69) mV in zeta potential, (97.31 ± 0.60)% in encapsulation efficiency, exhibiting spherical morphology and biphasic release process that a low burst effect within the first 0.5 hour and a relative-sustained release for the next several hours in PBS. These results indicate the oral delivery system of DTX-TPGS-PN was successfully built with good properties.
Chemistry, Pharmaceutical ; methods ; Particle Size ; Polyethylene Glycols ; chemistry ; Taxoids ; chemistry ; pharmacology ; Vitamin E ; analogs & derivatives ; chemistry

Rh is a very important blood group like ABO blood system in transfusion medicine. It causes severe transfusion reaction and hemolytic disease of the newborn (HDN) if RhD blood group does not match between the donor and the recipient. The population of RhD negative is only about 0.2% - 0.5% in Chinese. Conversion of RhD positive RBCs to RhD negative is very important in clinical transfusion. This study was to try to modify RhD antigen located on the surface of A, B, O and AB red blood cells in order to convert RhD positive to RhD negative by the modification of four kinds of methoxypolyethylene glycol (mPEG) derivatives and to observe the effect of mPEG modification on cell morphology, structure and function. The result demonstrated that modification efficiency of mPEG-BTC (mPEG-benzotriazole carbonate) was better than other three kinds of mPEG derivatives. It could camouflage RhD antigen efficiently when the concentration reached to 1 mmol/L. The result also showed that there were no harmful effects of mPEG modification on cell morphology, osmotic fragility, hemolysis, AchE, cholesterol, ATP, 2,3-DPG and deformability. It is suggested that success in converting RhD positive RBCs to RhD negative was preliminarily achieved.
Erythrocytes ; drug effects ; immunology ; physiology ; Humans ; Polyethylene Glycols ; pharmacology ; Rh-Hr Blood-Group System ; immunology

OBJECTIVETo investigate the effect of polyethylene oxide (PEO) on renal blood flow and its renoprotective effect in rabbits with endotoxin sepsis.

METHODSTwenty normal New Zealand white rabbits were randomly divided into normal saline (NS) group and PEO group (n=10), and endotoxin shock was induced by an intravenous injection of 0.6 mg/kg lipopolysaccharide. Resuscitation was performed when the blood pressure of the rabbits showed a 30% decline, using NS (in NS group) or the mixture of equal volumes of NS and 20 ng/g PEO (in PEO group) perfused at the rate of 5 ml/kg per hour. Before and during shock and at 1 h after resuscitation, the renal hemodynamics was monitored by ultrasound and the venous blood was extracted to examine the renal functions. The heart rate and arterial blood pressure were monitored throughout the experiment.

RESULTSThe rabbits in both groups showed a significantly lower renal artery blood flow velocity during the shock (P<0.05) with significantly increased pulsatility index (PI) and resistance index (RI) compared with those before the shock. One hour after resuscitation, the blood flow velocity in the renal arteries at all levels and the tertiary veins were reduced in NS group without obvious reduction of the PI and RI; in PEO group, the blood flow velocities in the renal arteries increased significantly compared to those before shock (P<0.05), and the PI and RI of the tertiary arteries were significantly lower than those in NS group (P<0.05). In both groups, BUN and Cr increased during endotoxin shock stage, and 1 h after resuscitation, PEO group showed significantly lower BUN and Cr levels than NS group (P<0.05).

CONCLUSIONA small dose of PEO can significantly promote renal perfusion in rabbits with septic shock, thus offering renoprotective effect against early damage in septicopyemia and septic shock.

Animals ; Hemodynamics ; Polyethylene Glycols ; pharmacology ; therapeutic use ; Rabbits ; Renal Circulation ; Shock, Septic ; drug therapy ; physiopathology

OBJECTIVETo study the effects of PEG stress on baicalin, baicalein accumulation induced by an increased concentration of PEG solution and the related genes' expression in suspension of Scutellaria baicalensis.

METHODThe content of baicalin, baicalein in suspension of S. baicalensis was determined by HPLC. The related genes' expression was analyzed by semi-quantitative PCR.

RESULTThe content of proline in suspension of S. baicalensis was promoted by PEG treatment. Ten percent PEG treatment promoted the expression of PAL and the content of baicalein in experimental material via a drought stress. 20% PEG solution treatment promoted the expression of UBGAT. At the same time, the increased activity of APX inhibited the progress of eliminating reactive oxygen by baicalein, which induced the transformation from baicalein to baicalin.

CONCLUSIONActive ingredient in suspension of S. baicalensis was promoted significantly via a stress of light concentration of PEG solution.

Flavonoids ; metabolism ; Gene Expression ; Polyethylene Glycols ; pharmacology ; Scutellaria baicalensis ; drug effects ; metabolism ; Suspensions

A new method for preparation of Hb solution free of stromal lipid was described. Almost all the lipid in fresh hemolysate of bovine red blood was removed with hydrophobic interaction chromatography (HIC) in the presence of 2% PEG4000, 5% PEG4000, 2%PEG10000 or 5%PEG10000. With the adding of 5%PEG4000, the 80% of recovery of Hb in HIC was obtained and the maximum lipid absorbed by hydrophobic medium, butyl agarose -6B was 86.6 mg/mL. The activity (P50) of hemoglobin preparation was 3386.4 Pa torrs, and the Hill number was 2.54, which were near to that of the native red blood cells. The mechanism of removing lipid by HIC and the function of PEG in the process were discussed.
Animals ; Cattle ; blood ; Hemoglobins ; isolation & purification ; Hydrophobic and Hydrophilic Interactions ; Lipids ; isolation & purification ; Polyethylene Glycols ; pharmacology

OBJECTIVETo acquire homozygous tetraploid germplasm of Rhodiola sachalinensis.

METHODPEG-mediated protoplast fusions were conducted using callus of Rh. sachalinensis as materials. Protoplast fusion products were embedded and cultured in low-density, low-melting-point agar and marked according to the protoplast size, and single-celled sister lines were established to acquire genetically homozygous tetraploid germplasm.

RESULTR(D) and R(M) of newborn daughter cells or protoplasm, metaphase cells or protoplasm were approximately in line with the formula R(D) = 0.793 7R(M). The change range in diameter of the diploid cells without fusion, two protoplasts fusion product were: 16.7 microm < or = R < 21.3 microm, 21.0 microm < or = R' < 26.8 microm respectively. There is an overlap between the two diameter ranges. The protoplast inoculation density of 1 x 10(4) cells x mL(-1) was appropriate when protoplasts were anchored by low-intensity, low-melting-point agar. Under the conditions of this density, plating efficiency was high and single cell origin of the sister lines microclones grew rapidly, and it was easy to mark the single cell microclones, and separate from each other to subculture. The chromosome counts results showed that chromosome numbers of diploid and tetraploid of single cell lines were 26 and 52, respectively. The result from flow cytometry assay showed that there is no presence of chimerism in single-cell regeneration plantlets.

CONCLUSIONThe results of this study provide a scientific basis for polyploid breeding of Rh. sachalinensis.

Cell Fusion ; methods ; Polyethylene Glycols ; pharmacology ; Polyploidy ; Protoplasts ; cytology ; drug effects ; Rhodiola ; cytology ; drug effects ; genetics

PUE@PEG-PLGA micelles has excellent characteristics such as small particle size, high drug loading and slow drug release. The results of TEM electron microscopy showed that PUE@PEG-PLGA micelles had obvious core-shell structure. The critical micelle concentration(CMC) of PEG-PLGA micelles determined by pyrene assay was about 4.8 mg·L~(-1). Laser confocal experiments showed that PEG-PLGA micelles can enhance the cellular uptake of coumarin-6 and aggregate around the mitochondria; quantitative results of extracellular drug residues also indirectly confirmed that PEG-PLGA micelles can promote cellular uptake of the drug. Acute ischemic myocardial model rats were prepared by coronary artery ligation, and then the model rats were randomly divided into six groups: Sham operation group, model group, puerarin(PUE) group, as well as low-, mid-, and high-dose PUE@PEG-PLGA micelles groups. Drugs were given by iv administration 5 min after the ligation. The ST segment changes in the electrocardiogram were monitored; serum creatine kinase(CK), lactate dehydrogenase(LDH), aspartate aminotransferase(AST), and malondialdehyde(MDA) levels were detected and myocardial infarct size was also measured. Both PUE and PUE@PEG-PLGA micelles can reduce the elevated ST segment, reduce serum CK, LDH, AST and MDA levels, and reduce myocardial infarct size. The efficacy of PUE@PEG-PLGA medium and high dose groups was significantly better than that in the PUE group, and the efficacy in PUE@PEG-PLGA low dose group was basically equivalent to that in the PUE group. PUE@PEG-PLGA micelles can greatly improve the cardiomyocytes uptake of PUE, enhance the anti-acute myocardial ischemia effect of drugs, and reduce its dosage.
Animals ; Isoflavones ; pharmacology ; Micelles ; Myocardial Ischemia ; drug therapy ; Polyesters ; Polyethylene Glycols ; Random Allocation ; Rats

OBJECTIVE: To construct a polylactic acid-glycolic acid-polyethylene glycol (PLGA-PEG) nanocarrier (N-Pac-CD133) coupled with a CD133 nucleic acid aptamer carrying paclitaxel for eliminating lung cancer stem cells (CSCs). METHODS: Paclitaxel-loaded N-Pac-CD133 was prepared using the emulsion/solvent evaporation method and characterized. CD133⁺ lung CSCs were separated by magnetic bead separation and identified for their biological behaviors and gene expression profile. The efficiency of paclitaxel-loaded N-Pac-CD133 for targeted killing of lung cancer cells was assessed in vitro. SCID mice were inoculated with A549 cells and received injections of normal saline, empty nanocarrier linked with CD133 aptamer (N-CD133), paclitaxel, paclitaxel-loaded nanocarrier (N-Pac) or paclitaxel-loaded N-Pac-CD133 (n=8, 5 mg/kg paclitaxel) on days 10, 15 and 20, and the tumor weight and body weight of the mice were measured on day 40. RESULTS: Paclitaxel-loaded N-Pac-CD133 showed a particle size of about 100 nm with a high encapsulation efficiency (>80%) and drug loading rate (>8%), and was capable of sustained drug release within 48 h. The CD133⁺ cell population in lung cancer cells showed the characteristic features of lung CSCs, including faster growth rate (30 days, P=0.001) and high expressions of tumor stem cell markers OV6(P < 0.001), CD133 (P=0.001), OCT3/4 (P=0.002), EpCAM (P=0.04), NANOG (P=0.005) and CD44 (P=0.02). Compared with N-Pac and free paclitaxel, paclitaxel-loaded N-Pac-CD133 showed significantly enhanced targeting ability and cytotoxicity against lung CSCs in vitro (P < 0.001) and significantly reduced the formation of tumor spheres (P < 0.001). In the tumor-bearing mice, paclitaxel-loaded N-Pac-CD133 showed the strongest effects in reducing the tumor mass among all the treatments (P < 0.001). CONCLUSION CD133 aptamer can promote targeted delivery of paclitaxel to allow targeted killing of CD133⁺ lung CSCs. N-Pac-CD133 loaded with paclitaxel may provide an effective treatment for lung cancer by targeting the lung cancer stem cells.
Animals ; Cell Line, Tumor ; Drug Carriers ; Lung ; Mice ; Mice, SCID ; Nanoparticles ; Neoplasms ; Neoplastic Stem Cells ; Paclitaxel/pharmacology* ; Polyethylene Glycols/pharmacology*

The aim of this study was to find an effective solution for difficulty of blood matching. Twenty nine cases with clinical difficult in blood matching were collected, classified by their etiological factors, and analyzed with all the antibodies in serum. RBC from health donor were incubated with mPEG-BTC at 25 degrees C for 1 hour. The coagulation of patient serum and donor RBC before and after mPEG-BTC camouflage was detected and compared by polybrene and antihuman globulin reagents. The result showed that 29 cases with difficult blood matching mainly suffered form blood diseases and tumors. The main antibody were Rh and autoantibody. Donor RBC modified by mPEG showed no coagulation with the blood serum in the patients with problems of blood matching. In conclusion, the modification of RBC with mPEG-BTC provides a useful strategy for resolving problem of clinical difficulty in blood matching.
Adolescent ; Adult ; Aged ; Blood Grouping and Crossmatching ; Erythrocytes ; immunology ; Female ; Humans ; Male ; Middle Aged ; Polyethylene Glycols ; pharmacology ; Triazoles ; pharmacology