-
[show abstract]
[hide abstract]
ABSTRACT: Methylenediphosphonate (MDP)-conjugated adriamycin liposomes (MDP-LADMs) were prepared using mild dynamic dialysis equilibrium method, and their targeted therapeutic effects against osteosarcomas and metastatic SOSP-M lung nodules were evaluated in vivo. The drug loading and encapsulation efficiency of the MDP-LADMs were measured via high-performance liquid chromatography, and their size and morphology of the MDP-LADMs were determined using transmission electron microscopy and a particle size analyzer, respectively. Cells apoptosis were evaluated by flow cytometry and caspase-3 activity. The targeted therapeutic effects of MDP-LADMs against UMR106 and SOSP-M osteosarcoma cells were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor growth and animal survival rates were evaluated after UMR106 osteosarcomas were established in Sprague-Dawley rats and SOSP-M pulmonary metastatic osteosarcoma model were established in nude mice, respectively. The results show that the average diameter of the MDP-LADMs was 152 ± 14 nm, and their ADM encapsulation efficiency was 91.7% with respect to a 250 μg/ml of loading efficiency. The conjugation efficiency between technetium-MDP and LADMs was 87.6%. Infrared spectra results of the samples dissolved in deuterated water confirmed that the methylenediphosphonate (MDP) was conjugated with LADMs through hydrogen bonding. The toxicity assay revealed a median lethal dose of 26.78 mg/kg for MDP-LADMs, which was significantly higher than doses observed for free ADM of 9.64 mg/kg (P < 0.05) and LADMs of 15.02 mg/kg(P < 0.05). Tumor growth and animal survival in the MDP-LADMs group were significantly higher than those in the ADM-only, MDP-only (P < 0.01) and LADMs groups (P < 0.05). These findings indicate that MDP-LADMs have higher therapeutic efficacy against osteosarcomas, demonstrate lower toxicity and their clearly targets osteosarcomas more clearly than the stand-alone systems, making them as a promising novel targeted therapy for the treatment of osteosarcoma.
Biomedical Microdevices 01/2012; 14(3):497-510. · 3.03 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Brain homeostasis is maintained by the blood-brain barrier (BBB), which prevents the entrance of circulating molecules and immune cells into the central nervous system. The BBB is formed by specialized brain endothelial cells that are connected by tight junctions (TJ). Previous studies have proven that the Tat protein of human immunodeficiency virus type 1 (HIV-1) alters TJ protein expression. However, the mechanisms by which the alterations occur have not been characterized in detail. In this study, primary human brain microvascular endothelial cells (HBMEC) were exposed to recombinant HIV-1 Tat protein, and the effects on occludin were observed. Tat treatment decreased occludin mRNA and protein levels. This effect was partially abrogated by addition of the RhoA inhibitor C3 exoenzyme and the p160-Rho-associated coiled kinase (ROCK) inhibitor Y-27632. Meanwhile, Tat also induced MMP-9 expression. RNA interference targeting MMP-9 reduced both the paracellular permeability of Tat-treated HBMEC and the concentration of soluble occludin in supernatants from the cells. Taken together, these results show that the HIV-1 Tat protein disrupts BBB integrity, at least in part by decreasing the production of occludin.
Brain research 12/2011; 1436:13-9. · 2.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Nanosized hemoglobin-based oxygen carriers are one of the most promising blood substitutes. In the present study, a comprehensive strategy for the preparation of nanosized cationic amylose-encapsulated hemoglobins (NCAHbs) was developed. First, cationic amylase (CA) was synthesized from amylose and quaternary ammonium salt by an etherification reaction. The structure of CA was characterized using Fourier transform infrared spectrophotometry (FTIR) and proton nuclear magnetic resonance spectrophotometry ((1)H NMR). The degree of substitution and the zeta potential were also measured. Then, the NCAHbs were prepared by electrostatic adhesion, reverse micelles and cross-linking. The UV-visible spectrophotometer was used to measure the entrapment efficiency (EE%) and drug loading efficiency (DL%) of the NCAHbs. Transmission electron microscopy and Malvern Nano-zs 90 analyzer were used to observe the size distribution and morphology of particles. Chemical structure was determined from the FTIR spectrum. A Hemox analyzer was used to measure the P(50) and Hill coefficients. A lethal hemorrhagic shock model in rats was used to evaluate the therapeutic effect of the NCAHbs. The results showed that the combined methods improved the size, stability, EE%, DL%, and oxygen-carrying capacity of the NCAHbs. The average diameter of the NCAHbs was 92.53 ± 3.64 nm, with a narrow polydispersity index of 0.027. The EE% was 80.05% ± 1.56% and DL% was 61.55% ± 1.41%. The P(50) and Hill coefficient were equal to 28.96 ± 1.33 mmHg and 2.55 ± 0.22, respectively. The size of NCAHbs remained below 200 nm for six days in PBS solution. The NCAHbs could effectively prevent lung injury from progressing to lethal hemorrhagic shock because they acted as both a volume expander and an oxygen carrier.
Biomaterials 08/2011; 32(35):9425-33. · 7.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Blood transfusion is a commonly supportive and complementary therapy for clinical emergencies and battle traumas. However, the blood compatibility, storage, transportation, and potential cross-infection have limited its applications. An efficient and stable hemoglobin-vesicle needs to be developed to substitute for the red blood cells. In this study, we prepared artificial red blood cells by encapsulating hemoglobin (Hb) with long-chain fatty-acids-grafted potato starch in a self-assembly way and evaluated their physical, chemical, and biological characteristics, hemoglobin leakage rate, and therapeutic effects in a rat hemorrhagic shock model. The starch was grafted with fatty acid in DMSO using potassium persulphate as catalyst, and hemoglobin was encapsulated into the grafted starch polymers under ultrasonic conditions. The encapsulation efficiency was polymers/hemoglobin ratio, time course, and ultrasound power dependent. The formed nanoparticles were assayed with Fourier transform infrared spectrophotometry (FTIR), transmission electron microscope (TEM), and nanosizer. The oxygen-carrying capability was assessed via oxygen half-saturation pressure (P(50)) and Hill coefficient determination. The final products were soluble and spherical with the average diameters of ∼250 nm. The hemoglobin leakage rate of the nanoparticles was ∼2.5% after storage for 60 days. The nanoparticles induced no complement C3 component activation when cocultured with murine serum. Meanwhile, no hemolysis and procoagulative phenomena were observed in vitro. When the nanoparticles were injected in the mice via tail vein, total platelet counts were not reduced. The rats with hemorrhagic shock recovered after artificial RBC supplement and the histological structures of main organs remained unchanged. Taken together, we prepared a novel and satisfactory artificial red blood cells with good oxygen-carrying capacity.
Biomacromolecules 03/2011; · 5.48 Impact Factor
-
Macromolecular Chemistry and Physics 10/2010; 211(21):2347 - 2355. · 2.36 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A novel chemical process has been devised for the synthesis of a new derivative of gossypol, 6,7,6',7'-tetrahydroxy-5,5'-diisopropyl-3,3'-dimethyl-[2,2']binaphthalenyl-1,4,1',4'-tetraone (Apogossypolone). This new process has only four steps, with a shorter synthesis span, a simple purification process, and improved yield and quality. The structure of apogossypolone was characterized by( 1)H-nuclear magnetic resonance, (13)C-nuclear magnetic resonance, mass spectroscopy, infrared spectroscopy, and elemental analysis. Cell-cytotoxicity assay demonstrates that apogossypolone is three- to six-fold more potent than the parent compound, (-)-gossypol, in inhibiting the human prostate tumor cell lines PC-3 and DU-145 as well as the human breast cancer cell line MDA-MB-231. The colony-formation assay with DU-145 cells showed that apogossypolone inhibited more than 70% of colony formation at 1 muM, whereas (-)-gossypol at 10 muM only inhibited less than 50% of colony formation. The results indicate that apogossypolone exerts strong antitumor activities in human prostate and breast cancer cells, and thus represents a promising cancer therapeutic.
Archiv der Pharmazie 05/2009; 342(4):223-9. · 1.71 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study sought to shed light on the killing effect of peripheral blood mononuclear cells (PBMCs) irradiated by gamma ray at a dose of 1 Gy on cultured human gastric tumor cell line MKN-28. The radiation dose rate of 17 Gy/min was used. The groups in the experiment were MKN-28 cell control group, PBMCs control group, MKN-28 tumor cells with irradiated or non-irradiated PBMCs co-cultured groups. Radiation dosage was one Gray, acridine orange/ethidium bromide (AO/EB) staining was used for observation of the killing effects of PBMCs on tumor cells in different period. Cells were harvested 240 h later and observed by transmission electron microscopy. The result showed the living period of irradiated PBMCs was shorter than that of non-irradiated PBMCs. In the irradiated and non-irradiated groups,a few PBMCs were still alive after being cultured for 240 h, but the cell volume was larger than that of lymphocytes. These cells were identified as monocytes (95%) or DCs (5%) by transmission electron microscopy. The co-culture of irradiated PBMCs and MKN-28 cells showed that tumor cells were eliminated after 96 h. As compared with the non-irradiated goup, the irradiated PBMCs had more potent ability for killing tumor. The results demonstrate that 1 Gy gamma irridiation can improve the killing effect of PBMCs on the tumor cells, and that 1 Gy gamma irritation can also induce shorter living period of lymphocytes in PBMCs cultured in vitro, but such irritation has little effect on the living period of monocytes and DCs in PBMCs.
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 03/2009; 26(1):144-7, 152.
-
[show abstract]
[hide abstract]
ABSTRACT: A novel magnetic polymer microsphere with amide groups and carboxyl groups was synthesized and reported here. The azidocarbonyl groups were derived from amide groups and linked to the proteins to investigate their immobilization capacity. The morphology, size, functional groups and magnetic properties of magnetic microspheres were characterized by optical microscopy, particle size analyzer, atom force microscopy, magnetic force microscopy, fourier transform infrared spectrometer, vibrating-sample magnetometer and thermal gravimetric analysis. The results indicated that the magnetic polymer microspheres had a well spherical shape with the size ranging from 1 to 10 μm, highly reactive functional groups, superparamagnetism and strong magnetic responsibility with saturation magnetization of 18.443 emu/g and Fe3O4 content around 21%. The immobilization capacity (η) was over 70%. The novel azidocarbonyl magnetic polymer microspheres showed potentials to be a good magnetic support and promising applications in bioseparation and biomedical fields. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Journal of Applied Polymer Science 02/2009; 112(4):2383 - 2390. · 1.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A novel immobilized enzyme system supported by poly(acrylic acid/N,N'-methylene-bisacryl-amide) hydrogel microspheres was prepared. This system exhibited characteristics of reversible pH-triggered release. The morphology, size, and chemical structure were examined through optical microscopy, particle size analyzer, and Fourier transform infrared spectrometer. Immobilization and release features were further investigated under different conditions, including pH, time, and microsphere quantity. Results showed the microspheres were regularly spherical with 3.8 approximately 6.6 microm diameter. Loading efficiencies of bovine serum albumin immobilized by gel entrapment and adsorption methods were 93.9% and 56.2%, respectively. The pH-triggered protein release of the system occurred when medium pH was above 6.0, while it was hardly detected when medium pH was below 6.0. Release efficiencies of entrapped and adsorbed protein were 6.38% and 95.0%, respectively. Hence, adsorption method was used to immobilize trypsin. Loading efficiency of 77.2% was achieved at pH 4.0 in 1 h. Release efficiency of 91.6% was obtained under optimum pH catalysis condition set at 8.0 and trypsin was free in solutions with retention activity of 63.3%. And 51.5% of released trypsin could be reloaded in 10 min. The results indicate this kind of immobilized enzyme system offers a promising alternative for enzyme recovery in biotechnology.
Applied biochemistry and biotechnology 11/2008; 158(3):747-60. · 1.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Novel fluorescent poly(styrene-acrylamide-acrylic acid) nanoparticles (FPSAAN) were synthesized by means of soapless emulsion polymerization and being modified with hydrazine hydrate by hydrazinolysis. The azidocarbonyl groups which can be rapidly coupled with proteins under mild condition were introduced onto the fluorescent nanoparticles by azido-reaction. Bovine serum albumin (BSA) was selected as a model protein to be covalently immobilized on the azidocarbonyl FPSAAN. Atom force microscopy (AFM), Transmission electron microscopy (TEM), Ultraviolet-visible (UV/Vis) spectrometer, Fourier transforms infrared spectrometer (FTIR), nanoparticle size analyzer and fluorescence spectrophotometer were used to characterize the FPSAAN. Results showed that FPSAAN had a regular spherical shape, and a dramatic narrow size distribution (polydispersity index 0.046 +/- 0.009). The fluorescence intensity of FPSAAN (lambda(ex)/lambda(em) = 253/306 nm), hydrazide-FPSAAN (lambda(ex/)lambda(em) = 260/326 nm), and protein-immobilized FPSAAN (lambda(ex)/lambda(em) = 258/325 nm) was linearly related to the concentration ranging from 1.0 x 10(-3) g l(-1) to 10.0 x 10(-3) g l(-1). The linear relationship was obtained. The equations are y = 52.808x + 16.465 (R (2) = 0.9927), y = 5.1814x + 4.1535 (R (2) = 0.9935) and y = 5.2227x + 5.2883 (R (2) = 0.9937), respectively. In addition, external factors such as pH and ionic strength exert a slight influence on fluorescent properties. The experiments of the immobilization of BSA indicated that FPSAAN with azidocarbonyl groups could be covalently coupled with BSA at the rate of 41.1%. Meanwhile, hCG antibody immobilized FPSAAN have the similar fluorescence characteristics to BSA immobilized FPSAAN. Only negligible difference of the fluorescence characteristics can be found. Furthermore, the fluorescence characteristics of hCG antibody immobilized FPSAAN have not been obviously affected after mixed with the hCG antigen and human plasma. These novel azidocarbonyl FPSAAN with stable fluorescence and active functional azidocarbonyl groups could be used as a promising fluorescent probe for quantitative detection, protein immobilization, cell labeling research and early rapid clinical diagnostics.
Journal of Materials Science Materials in Medicine 11/2008; 20(2):563-72. · 2.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release.
Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC.
The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found.
The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.
Journal of pharmacy & pharmaceutical sciences: a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 02/2008; 11(4):32-45. · 1.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Gelatin microspheres (GMs) containing Pingyangmycin hydrochloride were prepared for the interventional embolization by a double-phase emulsified thermal gelation method using oxidized dextran (ox-dex) as the cross-linking agent. The average diameter of the microspheres was 82 microm with 74% ranging from 50-200 microm. Drug content and the characteristics of drug release in vitro and in vivo were evaluated using UV-spectroscopy and HPLC, respectively. The prepared microspheres showed a rather high percentage of encapsulation ranging from 85 to 88% and drug content at 7.2%. The results of in vitro experiments showed that about 65.5% of the total amount of the encapsulated drug was released after 6 h at 37 degrees C. Experiments conducted through artery perfusion and artery embolization in rabbits revealed that the local drug concentration was significantly higher than the systemic blood-drug concentration, with a high level of local drug concentration maintained for more than 120 min after artery embolization with the Pingyangmycin-loaded ox-dex-GMs. The results indicated that the external carotid artery embolization with Pingyangmycin-loaded ox-dex-GMs at reduced dosages prolonged the local drug concentration at a higher level, and could achieve the purpose of a localized targeting tumor therapy. Compared with other embolization materials, ox-dex-GMs are an excellent alternative interventional embolization material for the treatment of head and neck tumors.
Journal of Biomedical Materials Research Part B Applied Biomaterials 08/2006; 78(1):56-62. · 2.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The H(2)O(2) supply strategy was one of crucial factors for high efficient degradation of pollutants with lignin peroxidase (LiP). In this paper, an attempt was made to couple a H(2)O(2) producing enzymatic reaction to the LiP catalyzed oxidation of dyes. H(2)O(2) needed was generated by glucose oxidase (GOD) and its substrate glucose. The generation rate of H(2)O(2) could be easily controlled by adjusting the pH of the degradation system and the amount of GOD added. Due to the controlled release of H(2)O(2), a sustainable constant activity of LiP was observed. The inhibition of LiP by high level H(2)O(2) supplied externally by a single addition at the beginning of the experiments could be avoided. Degradation of three dyes (xylene cyanol, fuchsine and rhodamine B) with LiP coupled with GOD indicated that the present H(2)O(2) supply strategy was very effective for improvement of the efficiency of the decolourization of dyes.
Journal of Biotechnology 07/2006; 123(4):483-90. · 3.05 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: CpG oligodeoxynucleotides (CpG ODN) have been shown to have potent adjuvant activity for a wide range of antigens. Of particular interest is their improved activity when closely associated with the antigen. The purpose of this study is to construct a nanovaccine coencapsulated with a gastric cancer specific antigen MG7 mimotope peptide and adjuvant CpG ODN 1645 using new nanotechnology as nanoemulsion and evaluate its immunocompetence. Nanoemulsion vaccine was prepared using magnetic ultrasound methods. BALB/c mice were immunized and the in vivo effectiveness was evaluated using tumor challenge assay. It was shown that the tumor masses formed in the mice immunized with coencapsulated nanovaccine (0.0825 g) markedly smaller (P < 0.01) than those formed in the mice immunized with nanovaccine encapsulated with antigen peptide alone (0.4465 g). A tumor inhibiting rate as high as 82.5% of the coencapsulated nanovaccine was obtained, while nanovaccine encapsulated with peptide only could not achieve the same effect (28.5%) (P < 0.01). Enzyme-linked immunospot assay (ELISPOT) showed that immunization using MG7 mimotope peptide coencapsulated with CpG ODN within the same nanoemulsion enhanced the frequency of splenocytes secreting IFN-gamma significantly (P < 0.01) when compared with immunization using MG7 peptide encapsulated in nanoemulsion alone (197spots/1 x 10(6) vs. 73 spots/1 x 10(6)). Cellular ELISA indicated that serum titer of antibody against MG7-Ag was significantly higher (P < 0.01) in mice immunized with coencapsulation form nanovaccine (0.7884) than that in the group immunized with nanovaccine encapsulated with MG7 peptide alone (0.3616). Using intracellular flow cytometric analysis, it was found that the IFN-gamma response was contributed by CD4+ T-cells. Our experiments suggest that a vaccinal approach using nano-delivery system carrying in tumoral epitope and CpG ODN as adjuvant may have important implications for cancer therapy.
Cancer biology & therapy 02/2005; 4(2):218-24. · 2.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pingyangmycin gelatin microspheres(PYM-GMS) was prepared by optimal double-phase emulsified condensation polymerization for the interventional Chemoembolization with carotid artery therapy, and its release characteristics were studied in vivo and in vitro. The results of three ways of administration(vein drop, artery perfusion and artery embolization) were compared. The experiment indicates that the diameter of PYM-GMS is more appropriate for the application in external carotid artery embolization with PYM-GMS, which significantly reduces the circulating drug level and the dosage, prolongs the time period of higher drug concentration, achieves the purpose of sustained release and targeted tumor therapy.
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 01/2004; 20(4):646-9.
-
[show abstract]
[hide abstract]
ABSTRACT: In this symposium, we reviewed the principle and development of time-resolved fluorescence anisotropy measurement. Its method of measurement, characteristics and applications in the research of biomacromolecule, configuration and molecular structure have been discussed. Its potential applications are also illustrated.
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 01/2003; 19(4):712-4.
-
[show abstract]
[hide abstract]
ABSTRACT: This paper reviews recent research and development on microwave sterilization, including the experiments of sterilization effects, the influence of microwave radiating on the media parameters, the development of microwave sterilizers and the study of sterilization mechanism. Many results show that the method of microwave sterilization is more easy-to-perform, economical and reproducible than the conventional autoclaving method. It is necessary to study the sterilization conditions through the experiments for different media and bacteria. The research on sterilization mechanism, especially non-thermal sterilization mechanism is still a hotpoint.
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 07/2002; 19(2):334-6, 343.
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the extracted process of gossypol acetic acid (G-AA) from cottonseed soapstock and explore the improvement of its yield and purity, a novel ultrasound-assisted extraction and crystallization method was introduced to this process. Under the optimized conditions, preliminary G-AA with the yield of 1300 mg and the purity of 95.9% could be obtained from 100 g of fresh soapstock by ultrasound-assisted extraction. In addition, UV, IR, and NMR spectrum further confirmed the detailed chemical structure of G-AA. Assay of inhibiting human prostate tumor cell line PC-3 and human breast cancer cell line MDA-MB-231 revealed its biological activity, the values of IC 50 are 9.096 Μmol/L and 14.37 Μmol/L respectively. In comparison with the conventional solvent extraction, this novel process increases the content of G-AA over 90%, reduces the time of crystallization by 75%, and retains the anticancer activity of gossypol. © 2009 American Institute of Chemical Engineers AIChE J, 2009 Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/61872/1/11700_ftp.pdf
