共查询到20条相似文献,搜索用时 15 毫秒
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Ferreira AL Salvadori DM Nascimento MC Rocha NS Correa CR Pereira EJ Matsubara LS Matsubara BB Ladeira MS 《Mutation research》2007,631(1):26-35
Doxorubicin (DOX) is an efficient chemotherapeutic agent used against several types of tumors; however, its use is limited due to severe cardiotoxicity. Since it is accepted that reactive oxygen species are involved in DOX-induced cardiotoxicity, antioxidant agents have been used to attenuate its side effects. To determine tomato-oleoresin protection against cardiac oxidative DNA damage induced by DOX, we distributed Wistar male rats in control (C), lycopene (L), DOX (D) and DOX+lycopene (DL) groups. They received corn oil (C, D) or tomato-oleoresin (5mg/kg body wt. day) (L, DL) by gavage for a 7-week period. They also received saline (C, L) or DOX (4mg/kg body wt.) (D, DL) intraperitoneally at the 3rd, 4th, 5th, and at 6th week. Lycopene absorption was checked by HPLC. Cardiac oxidative DNA damage was evaluated by the alkaline Comet assay using formamidopyrimidine-DNA glycosylase (FPG) and endonuclease III (endo III). Cardiomyocyte levels of SBs, SBs FPG and SBs Endo III were higher in rats from D when compared to other groups. DNA damage levels in cardiomyocytes from DL were not different when compared to C and L groups. The viability of cardiomyocytes from D or DL was lower than C or L groups (p<0.01). Lycopene levels (mean+/-S.D.nmol/kg) in saponified hearts were similar between L (47.43+/-11.78) and DL (49.85+/-16.24) groups. Our results showed: (1) lycopene absorption was confirmed by its cardiac levels; (2) DOX-induced oxidative DNA damage in cardiomyocyte; (3) tomato-oleoresin supplementation protected against cardiomyocyte oxidative DNA damage. 相似文献
3.
Jia Lin Sarah Shigdar Ding Zhi Fang Dognxi Xiang Ming Q. Wei Andrew Danks Lingxue Kong Lianghong Li Liang Qiao Wei Duan 《PloS one》2014,9(7)
As a glycosphingolipid that can bind to several extracellular matrix proteins, sulfatide has the potential to become an effective targeting agent for tumors overexpressing tenasin-C in their microenvironment. To overcome the dose-limiting toxicity of doxorubicin (DOX), a sulfatide-containing nanoliposome (SCN) encapsulation approach was employed to improve treatment efficacy and reduce side effects of free DOX. This study analysed in vitro characteristics of sulfatide-containing nanoliposomal DOX (SCN-DOX) and assessed its cytotoxicity in vitro, as well as biodistribution, therapeutic efficacy, and systemic toxicity in a human glioblastoma U-118MG xenograft model. SCN-DOX was shown to achieve highest drug to lipid ratio (0.5∶1) and a remarkable in vitro stability. Moreover, DOX encapsulated in SCN was shown to be delivered into the nuclei and displayed prolonged retention over free DOX in U-118MG cells. This simple two-lipid SCN-DOX nanodrug has favourable pharmacokinetic attributes in terms of prolonged circulation time, reduced volume of distribution and enhanced bioavailability in healthy rats. As a result of the improved biodistribution, an enhanced treatment efficacy of SCN-DOX was found in glioma-bearing mice compared to the free drug. Finally, a reduction in the accumulation of DOX in the drug''s principal toxicity organs achieved by SCN-DOX led to the diminished systemic toxicity as evident from the plasma biochemical analyses. Thus, SCN has the potential to be an effective and safer nano-carrier for targeted delivery of therapeutic agents to tumors with elevated expression of tenascin-C in their microenvironment. 相似文献
4.
Telechelic water-soluble HPMA copolymers and HPMA copolymer-doxorubicin (DOX) conjugates have been synthesized by RAFT polymerization mediated by a new bifunctional chain transfer agent (CTA) that contains an enzymatically degradable oligopeptide sequence. Postpolymerization aminolysis followed by chain extension with a bis-maleimide resulted in linear high molecular weight multiblock HPMA copolymer conjugates. These polymers are enzymatically degradable; in addition to releasing the drug (DOX), the degradation of the polymer backbone resulted in products with molecular weights similar to the starting material and below the renal threshold. The new multiblock HPMA copolymers hold potential as new carriers of anticancer drugs. 相似文献
5.
Zhan F Chen W Wang Z Lu W Cheng R Deng C Meng F Liu H Zhong Z 《Biomacromolecules》2011,12(10):3612-3620
Endosomal pH-activatable doxorubicin (DOX) prodrug nanogels were designed, prepared, and investigated for triggered intracellular drug release in cancer cells. DOX prodrugs with drug grafting contents of 3.9, 5.7, and 11.7 wt % (denoted as prodrugs 1, 2, and 3, respectively) were conveniently obtained by sequential treatment of poly(ethylene glycol)-b-poly(2-hydroxyethyl methacrylate-co-ethyl glycinate methacrylamide) (PEG-b-P(HEMA-co-EGMA)) copolymers with hydrazine and doxorubicin hydrochloride. Notably, prodrugs 1, 2, and 3 formed monodispersed nanogels with average sizes of 114.4, 75.3, and 66.3 nm, respectively, in phosphate buffer (PB, 10 mM, pH 7.4). The in vitro release results showed that DOX was released rapidly and nearly quantitatively from DOX prodrug nanogels at endosomal pH and 37 °C in 48 h, whereas only a minor amount (ca. 20% or less) of drug was released at pH 7.4 under otherwise the same conditions. Confocal laser scanning microscope (CLSM) observations revealed that DOX prodrug nanogels delivered and released DOX into the cytosols as well as cell nuclei of RAW 264.7 cells following 24 h incubation. MTT assays demonstrated that prodrug 3 had pronounced cytotoxic effects to tumor cells following 72 h incubation with IC(50) data determined to be 2.0 and 3.4 μg DOX equiv/mL for RAW 264.7 and MCF-7 tumor cells, respectively. The corresponding polymer carrier, PEG-b-P(HEMA-co-GMA-hydrazide), was shown to be nontoxic up to a tested concentration of 1.32 mg/mL. These endosomal pH-activatable DOX prodrug nanogels uniquely combining features of water-soluble macromolecular prodrugs and nanogels offer a promising platform for targeted cancer therapy. 相似文献
6.
Terpolymerization of poly(ethylene glycol) (PEG), divinyl ethers, and serinol can be used to synthesize water soluble, hydrolytically labile, amino-pendent polyacetals (APEGs) suitable for drug conjugation. As these polyacetals display pH-dependent degradation (with faster rates of hydrolysis at acidic pH) and they are not inherently hepatotropic after intravenous (iv) injection, they have potential for development as biodegradable carriers to facilitate improved tumor targeting of anticancer agents. The aim of this study was to synthesize a polyacetal-doxorubicin (APEG-DOX) conjugate, determine its cytotoxicity in vitro and evaluate its potential for improved tumor targeting in vivo compared to an HPMA copolymer-DOX conjugate in clinical development. Amino-pendent polyacetals were prepared, and following succinoylation (APEG-succ), the polymeric intermediate conjugated to DOX via one of three methods using carbodiimide mediated coupling (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in aqueous solution was the most successful). The resultant APEG-DOX conjugates had a DOX content of 3.0-8.5 wt %, contained <1.2% free DOX (relative to total DOX content) and had a M(w) = 60000-100000 g/mol and M(w)/M(n) = 1.7-2.6. In vitro cytotoxicity studies showed APEG-DOX to be 10-fold less toxic toward B16F10 cells than free DOX (IC(50) = 6 microg/mL and 0.6 microg/mL respectively), but confirmed the serinol-succinoyl-DOX liberated during main-chain degradation to be biologically active. When administered iv to C57 black mice bearing subcutaneous (sc) B16F10 melanoma, APEG-DOX of M(w) = 86000 g/mol, and 5.0 wt % DOX content exhibited significantly (p < 0.05) prolonged blood half-life and enhanced tumor accumulation compared to an HPMA copolymer-GFLG-DOX conjugate of M(w) = 30000 g/mol and 6.2 wt % DOX content. Moreover, APEG-DOX exhibited lower uptake by liver and spleen. These observations suggest that APEG anticancer conjugates warrant further development as novel polymer therapeutics for improved tumor targeting. 相似文献
7.
Reduction-sensitive reversibly core-cross-linked micelles were developed based on poly(ethylene glycol)-b-poly(N-2-hydroxypropyl methacrylamide)-lipoic acid (PEG-b-PHPMA-LA) conjugates and investigated for triggered doxorubicin (DOX) release. Water-soluble PEG-b-PHPMA block copolymers were obtained with M(n,PEG) of 5.0 kg/mol and M(n,HPMA) varying from 1.7 and 4.1 to 7.0 kg/mol by reversible addition-fragmentation chain transfer (RAFT) polymerization. The esterification of the hydroxyl groups in the PEG-b-PHPMA copolymers with lipoic acid (LA) gave amphiphilic PEG-b-PHPMA-LA conjugates with degrees of substitution (DS) of 71-86%, which formed monodispersed micelles with average sizes ranging from 85.3 to 142.5 nm, depending on PHPMA molecular weights, in phosphate buffer (PB, 10 mM, pH 7.4). These micelles were readily cross-linked with a catalytic amount of dithiothreitol (DTT). Notably, PEG-b-PHPMA(7.0k)-LA micelles displayed superior DOX loading content (21.3 wt %) and loading efficiency (90%). The in vitro release studies showed that only about 23.0% of DOX was released in 12 h from cross-linked micelles at 37 °C at a low micelle concentration of 40 μg/mL, whereas about 87.0% of DOX was released in the presence of 10 mM DTT under otherwise the same conditions. MTT assays showed that DOX-loaded core-cross-linked PEG-b-PHPMA-LA micelles exhibited high antitumor activity in HeLa and HepG2 cells with low IC(50) (half inhibitory concentration) of 6.7 and 12.8 μg DOX equiv/mL, respectively, following 48 h incubation, while blank micelles were practically nontoxic up to a tested concentration of 1.0 mg/mL. Confocal laser scanning microscope (CLSM) studies showed that DOX-loaded core-cross-linked micelles released DOX into the cell nuclei of HeLa cells in 12 h. These reduction-sensitive disassemblable core-cross-linked micelles with excellent biocompatibility, superior drug loading, high extracellular stability, and triggered intracellular drug release are promising for tumor-targeted anticancer drug delivery. 相似文献
8.
Salama R Alalouf O Tabachnikov O Zolotnitsky G Shoham G Shoham Y 《FEBS letters》2012,586(16):2436-2442
In this study we demonstrate that the abp gene in Geobacillus stearothermophilus T-6 encodes a family 27 glycoside hydrolase β-L-arabinopyranosidase. The catalytic constants towards the chromogenic substrate pNP-β-L-arabinopyranoside were 0.8±0.1 mM, 6.6±0.3 s(-1), and 8.2±0.3 s(-1) mM(-1) for K(m), k(cat) and k(cat)/K(m), respectively. (13)C NMR spectroscopy unequivocally showed that Abp is capable of removing β-L-arabinopyranose residues from the natural arabino-polysaccharide, larch arabinogalactan. Most family 27 enzymes are active on galactose and contain a conserved Asp residue, whereas in Abp this residue is Ile67, which shifts the specificity of the enzyme towards arabinopyranoside. 相似文献
9.
Intracellular drug delivery is an important rout to reverse drug resistance of tumor cells. In this study, the linoleic acid (LA)-grafted chitosan oligosaccharide (CSO) was synthesized to construct a micellar delivery system for intracellular delivery. The synthesized linoleic acid-grafted chitosan oligosaccharide (CSO-LA) with 10.3% graft ratio of LA could form micelles in aqueous with 86.69 μg/ml critical micellar concentration (CMC). The CSO-LA micelle had 46.2±3.6 nm number average diameter and 36.0±3.3 mV zeta potential. Taking doxorubicin base (DOX) as a model drug, the drug-loaded CSO-LA micelles (CSO-LA/DOX) was then prepared. The drug encapsulation efficiencies of CSO-LA/DOX were as high as 80%, and the drug loading capacity could be improved by increasing the charged DOX. Using MCF-7, Doxorubicin·HCl resistant MCF-7 (MCF-7/ADR), K562 and Doxorubicin·HCl resistant K562 (K562/ADR) cells as model drug sensitive and drug resistant tumor cells, the experiments demonstrated the CSO-LA had excellent cellular uptake ability by either drug sensitive tumor cells or drug resistance tumor cells. The CSO-LA micelles could deliver DOX into tumor cells, and the DOX in cells was increased with incubation time. As a result, the cytotoxicities of DOX encapsulated in CSO-LA micelles against drug resistance tumor cells were improved significantly, comparing to that of Doxorubicin·HCl solution. 相似文献
10.
Hollow chitosan/poly(acrylic acid) nanospheres as drug carriers 总被引:1,自引:0,他引:1
The preparation, in-vitro release, in-vitro cytotoxicity, and in-vivo drug delivery of doxorubicin (DOX)-loaded chitosan (CS)-poly(acrylic acid) (PAA) hollow nanospheres were investigated. The loading was done by dissolving a certain amount of DOX in non-cross-linked CS-PAA nanospheres aqueous solution followed by cross-linking chitosan with glutaraldehyde. The drug-loading content was up to 4.3% and the size of drug-loaded hollow nanospheres, determined by dynamic light scattering, was 118 nm. The nanospheres showed a continuous release of the entrapped DOX up to 10 days in vitro and showed comparable in-vitro cytotoxicity against HepG2 cells compared to the free DOX. In-vivo DOX delivery of DOX-loaded CS-PAA nanospheres showed that DOX concentration in blood can be maintained for a longer period than free DOX solution, and the DOX concentration in mice liver can be maintained constantly at relatively high level. The interesting feature of DOX-loaded CS-PAA hollow nanopspheres is that the loaded DOX can be delivered into the mice brain. The confocal laser scanning microscopy analysis reveals that fluorescein isothiocyanate (FITC)-labeled CS-PAA can deposit in different organs including liver, spleen, and brain. 相似文献
11.
Talelli M Morita K Rijcken CJ Aben RW Lammers T Scheeren HW van Nostrum CF Storm G Hennink WE 《Bioconjugate chemistry》2011,22(12):2519-2530
Doxorubicin is an anthracycline anticancer agent that is commonly used in the treatment of a variety of cancers, but its application is associated with severe side effects. Biodegradable and thermosensitive polymeric micelles based on poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide-lactate] (mPEG-b-p(HPMAmLac(n))) have been studied as drug delivery systems for therapeutic and imaging agents and have shown promising in vitro and in vivo results. The purpose of this study was to investigate the covalent coupling of a doxorubicin-glucuronide prodrug (DOX-propGA3) to the core of mPEG-b-p(HPMAmLac(2)) micelles. This prodrug is specifically activated by human β-glucuronidase, an enzyme that is overexpressed in necrotic tumor areas. To this end, an azide modified block copolymer (mPEG(5000)-b-p(HPMAmLac(2)-r-AzEMA)) was synthesized and characterized, and DOX-propGA3 was coupled to the polymer via click chemistry with a high (95%) coupling efficiency. Micelles formed by this DOX containing polymer were small (50 nm) and monodisperse and released 40% of the drug payload after 5 days incubation at 37 °C in the presence of β-glucuronidase, but less than 5% in the absence of the enzyme. In vitro cytotoxicity experiments demonstrated that DOX micelles incubated with 14C cells showed the same cytotoxicity as free DOX only in the presence of β-glucuronidase, indicating full conversion of the polymer-bound DOX into the parent drug. Overall, this novel system is very promising for enzymatically responsive anticancer therapy. 相似文献
12.
Hydroxychloroquine (HCQ) inhibits autophagy and therefore can sensitize some cancer cells to chemotherapy, but the high doses required limit its clinical use. Here we show that loading HCQ into liposomes (HCQ/Lip) decorated with a pH-sensitive TH-RGD targeting peptide (HCQ/Lip-TR) can concentrate HCQ in B16F10 tumor cells and lysosomes. HCQ/Lip-TR was efficiently internalized as a result of its ability to bind ITGAV-ITGB3/integrin αvβ3 receptors highly expressed on the tumor cell surface and to undergo charge reversal from anionic at pH 7.4 to cationic at pH 6.5. Studies in vitro at pH 6.5 showed that the intracellular HCQ concentration was 35.68-fold higher, and lysosomal HCQ concentration 32.22-fold higher, after treating cultures with HCQ/Lip-TR than after treating them with free HCQ. The corresponding enhancements observed in mice bearing B16F10 tumors were 15.16-fold within tumor cells and 14.10-fold within lysosomes. HCQ/Lip-TR was associated with milder anemia and milder myosuppressive reductions in white blood cell and platelet counts than free HCQ, as well as less accumulation in the small intestine, which may reduce risk of intestinal side effects. In addition, co-delivering HCQ/Lip-TR with either free doxorubicin (DOX) or liposomal DOX improved the ability of DOX to inhibit tumor growth. Biochemical, electron microscopy and immunofluorescence experiments confirmed that HCQ/Lip-TR blocked autophagic flux in tumor cells. Our results suggest that loading HCQ into Lip-TR liposomes may increase the effective concentration of the inhibitor in tumor cells, allowing less toxic doses to be used. 相似文献
13.
Pires PW Rogers CT McClain JL Garver HS Fink GD Dorrance AM 《American journal of physiology. Heart and circulatory physiology》2011,301(1):H87-H97
Matrix metalloproteases (MMPs) are a family of zinc peptidases involved in extracellular matrix turnover. There is evidence that increased MMP activity is involved in remodeling of resistance vessels in chronic hypertension. Thus we hypothesized that inhibition of MMP activity with doxycycline (DOX) would attenuate vascular remodeling. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with DOX (50 mg·kg(-1)·day(-1) in the drinking water) for 6 wk. Untreated SHRSP were controls. Blood pressure was measured by telemetry during the last week. Middle cerebral artery (MCA) and mesenteric resistance artery (MRA) passive structures were assessed by pressure myography. MMP-2 expression in aortas was measured by Western blot. All results are means ± SE. DOX caused a small increase in mean arterial pressure (SHRSP, 154 ± 1; SHRSP + DOX, 159 ± 3 mmHg; P < 0.001). Active MMP-2 expression was reduced in aorta from SHRSP + DOX (0.21 ± 0.06 vs. 0.49 ± 0.13 arbitrary units; P < 0.05). In the MCA, at 80 mmHg, DOX treatment increased the lumen (273.2 ± 4.7 vs. 238.3 ± 6.3 μm; P < 0.05) and the outer diameter (321 ± 5.3 vs. 290 ± 7.6 μm; P < 0.05) and reduced the wall-to-lumen ratio (0.09 ± 0.002 vs. 0.11 ± 0.003; P < 0.05). Damage after transient cerebral ischemia (transient MCA occlusion) was reduced in SHRSP + DOX (20.7 ± 4 vs. 45.5 ± 5% of hemisphere infarcted; P < 0.05). In the MRA, at 90 mmHg DOX, reduced wall thickness (29 ± 1 vs. 22 ± 1 μm; P < 0.001) and wall-to-lumen ratio (0.08 ± 0.004 vs. 0.11 ± 0.008; P < 0.05) without changing lumen diameter. These results suggest that MMPs are involved in hypertensive vascular remodeling in both the peripheral and cerebral vasculature and that DOX reduced brain damage after cerebral ischemia. 相似文献
14.
Sultana R Di Domenico F Tseng M Cai J Noel T Chelvarajan RL Pierce WD Cini C Bondada S St Clair DK Butterfield DA 《Journal of proteome research》2010,9(12):6232-6241
Doxorubicin (DOX) is an anticancer drug used for the treatment of solid tumors. The ability of DOX to treat cancer is not specific to cancer cells; some of the cells that are normal may also become targets of DOX, thereby altering the normal cellular functions and eventual cell loss. DOX effects have been studied in detail in heart because of its ability to cause cardiomyopathy. The exact mechanism of DOX-induced cardiomyopathy is not completely understood. One of organs that can be affected by DOX is thymus. DOX treatment leads to degeneration of thymus; however, since thymus undergoes age-dependent degeneration, researchers have understudied the effect of DOX on thymus. In the present investigation, we studied the effects of DOX on thymus, an organ that is important for the T-cell maturation. DOX treatment led to loss of cortical cells, decrease lymphopoiesis and increased the number of Hassells corpuscles, a marker of thymus aging. Proteomics analysis led to identification of a number of thymic proteins whose expression are altered by in vivo DOX treatment. Taken together, these results are consistent with the notion that DOX-treatment leads to thymic senescence. 相似文献
15.
Koçkar MC Nazıroğlu M Celik O Tola HT Bayram D Koyu A 《Cell biochemistry and function》2010,28(8):673-677
Doxorubicin (DOX) is a chemotherapeutic agent, and is widely used in cancer treatment. The most common side effect of DOX was indicated on cardiovascular system by experimental studies. There are some studies suggesting oxidative stress-induced toxic changes on liver related to DOX administration. The aim of the present study was to evaluate whether antioxidant N-acetylcysteine (NAC) relieves oxidative stress in DOX- induced liver injury in rat. Twenty-four male rats were equally divided into three groups. First group was used as a control. Second group received single dose of DOX. NAC for 10 days was given to constituting the third group after giving one dose of DOX. After 10 days of the experiment, liver tissues were taken from all animals. Lipid peroxidation (LP) levels were higher in the DOX group than in control whereas LP levels were lower in the DOX+NAC group than in control. Vitamin C and vitamin E levels were lower in the DOX group than in control whereas vitamin C and vitamin E levels were higher in the DOX+NAC group than in the DOX group. Reduced glutathione levels were higher in the DOX+NAC group than in control and DOX group. Glutathione peroxidase, vitamin A and β-carotene values were not changed in the three groups by DOX and NAC administrations. In histopathological evaluation of DOX group, there were mononuclear cell infiltrations, vacuolar degeneration, hepatocytes with basophilic nucleus and sinusoidal dilatations. The findings were totally recovered by NAC administration. In conclusion, N-acetylcysteine induced modulator effects on the doxorubicin-induced hepatoxicity by inhibiting free radical production and supporting the antioxidant vitamin levels. 相似文献
16.
Effects of cis-unsaturated fatty acids on doxorubicin sensitivity in P388/DOX resistant and P388 parental cell lines 总被引:9,自引:0,他引:9
It has been reported that several cis-unsaturated fatty acids (c-UFAs) could increase doxorubicin (DOX) accumulation in cancer cells and hence elevate its cytotoxicity. However, some researchers showed that c-UFA pretreatment did not affect its cytotoxicity in special cell lines. It is possible that the different results occurred due to different cellular characteristics. We hypothesized that c-UFA treatment might modulate the activities of some antioxidant enzymes to affect the resistance of cells to DOX. In the present study, we examined how c-UFA pretreatment affected DOX cytotoxicity on mouse leukemia cell line, P388, and its resistant subline, P388/DOX, which we found to have significantly higher glutathione peroxidase (GPx) activity as well as P-glycoprotein (p-gp) overexpression. We chose two c-UFAs, gamma-linolenic acid (GLA) (18:3n-6) and docosahexaenoic acid (DHA) (22:6n-3). Cytotoxicity was measured by MTT (3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and trypan blue exclusion assays. DOX accumulation and p-gp expression were measured by flow cytometry. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and GPx were determined for both cell lines with and without treatment with GLA or DHA. Significant DOX accumulation occurred in both cell lines with GLA or DHA pretreatment, but without any change in p-gp expression in either cell line. Sensitivity to DOX cytotoxicity was improved by GLA or DHA pretreatment in P388/DOX in which only SOD activity was significantly increased, but not in the parental cell line P388 in which both SOD and CAT were significantly increased by the pretreatment. However, combined pretreatment of GLA or DHA with antioxidants, pyrrolidinedithiocarbamate (PDTC) or Vitamin C, could sensitize not only P388/DOX but also P388 cells to DOX. We conclude that the effects of c-UFA pretreatment on the sensitivity of cancer cells to DOX not only depend on the change in drug accumulation but also the change in the levels of antioxidant enzyme activities, and suggest that combined administration of c-UFAs, antioxidants, and DOX may be more effective in treating leukemia. 相似文献
17.
Shaoning Wang Hui Xu Jinghua Xu Ying Zhang Yingchun Liu Yi-hui Deng Dawei Chen 《AAPS PharmSciTech》2010,11(2):870-877
In this study, a cleavable PEG-lipid (methoxypolyethyleneglycol 2000-cholesteryl hemisuccinate, PEG2000-CHEMS) linked via ester bond and galactosylated lipid ((5-cholesten-3β-yl) 4-oxo-4-[2-(lactobionyl amido) ethylamido] butanoate, CHS-ED-LA) were used to modify doxorubicin (DOX) liposome. DOX
was encapsulated into conventional liposomes (CL), galactosylated liposomes (modified with CHS-ED-LA, GalL), pegylated liposomes
(modified with PEG2000-CHEMS, PEG-CL), and pegylated galactosylated liposomes (modified with CHS-ED-LA and PEG2000-CHEMS, PEG-GalL) using an ammonium sulfate gradient loading method and then intravenously injected to normal mice. Both PEG-GalL
DOX and GalL DOX gave relatively high overall drug targeting efficiencies to liver ((T
e)liver) and were mainly taken up by hepatocyte. However, PEG-GalL DOX showed unique “sustained targeting” characterized by slowed
transfer of DOX to liver and reduced peak concentrations in the liver. The biodistribution and antitumor efficacy of various
DOX preparations were studied in hepatocarcinoma 22 (H22) tumor-bearing mice. The inhibitory rate of PEG-GalL DOX to H22 tumors
was up to 94%, significantly higher than that of PEG-CL DOX, GalL DOX, CL DOX, and free DOX, although the tumor distribution
of DOX revealed no difference between PEG-GalL DOX and PEG-CL DOX. Meanwhile, the gradual increase in the liver DOX concentration
due to the sustained uptake of PEG-GalL DOX formulations resulted in lower damage to liver. In conclusion, the present investigation
indicated that double modification of liposomes with PEG2000-CHEMS, and CHS-ED-LA represents a potentially advantageous strategy in the therapy of liver cancers or other liver diseases. 相似文献
18.
Effect of Boron on the Incorporation of Glucose from UDP-Glucose into Cotton Fibers Grown in Vitro 总被引:3,自引:3,他引:0
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Boron is required for fiber growth and development in cotton ovules cultured in vitro. Incorporation of [14C]glucose by such fiber from supplied UDP-[14C]glucose into the hot alkali-insoluble fraction is rapid and linear for about 30 minutes. Incorporation of [14C]glucose from such substrate by fibers grown in boron-deficient ovule cultures is much less than in the case with fibers from ovules cultured with boron in the medium. Total products (alkali-soluble plus alkali-insoluble fractions) were also greater in fibers from ovules cultured with boron. The fraction insoluble in acetic-nitric reagent was a small part of the total glucans; however, in the boron-sufficient fibers, there was significantly more of this fraction than in fibers from boron-deficient ovule cultures. The hot water-soluble glucose polymers from the labeled fibers had a significant fraction of the total [14C]glucose incorporated from UDP-[14C]glucose. Both β-1,4- and β-1,3- water-soluble polymers were formed in the boron-sufficient fibers, whereas the same water-soluble fraction from the boron-deficient fibers was predominantly β-1,3-polymers. The incorporation of [14C]glucose from GDP-[14C]glucose by the fibers attached to the ovules was insignificant. 相似文献
19.
This paper demonstrates that miscible blends from water-insoluble polymers, such as poly(2,4,4-trimethylhexamethylene terephthalamide) (1), methylamine imidized poly(methyl methacrylate) (2), and aromatic poly(ether sulfone) (3) and water-soluble polymers, such as poly(2-ethyl-2-oxazoline) (4) and poly(N-vinyl pyrrolidone) (5), respectively, represent a new class of supramolecular hydrogels. When the degree of polymerization (DP) of the water-soluble polymer is larger than that of water-insoluble polymer, the resulting hydrogels adsorb extremely high amounts of water (i.e., 229 wt % in the case of the hydrogel 1/4) and remain mechanically tough. The high water uptake capability of these blends is explained by a supramolecular network structure generated by H-bonding and/or other noncovalent interactions between the water-insoluble hydrophobic polymer and water-soluble hydrophilic segments as reversible cross-linking points interconnected by hydrophilic water soluble segments. The glass transition temperatures of these hydrogels are tailored via the ratio between the weight percent of the two polymers and by the glass transition temperature of the parent polymers. These supramolecular hydrogels can be processed from melt or solution and maintain excellent mechanical properties both in dry and in the water swollen state. This class of hydrogels is of interest for areas such as membranes, contact lenses, tissue engineering, and other biomedical applications. 相似文献
20.
Zhang R Yang D Zhou C Cheng K Liu Z Chen L Fang L Xie P 《Analytical biochemistry》2012,427(2):116-120
Western blot analysis is a commonly used technique for determining specific protein levels in clinical samples. For normalization of protein levels in Western blot, a suitable loading control is required. On account of its relatively high and constant expression, β-actin has been widely employed in Western blot of cell cultures and tissue extracts. However, β-actin's presence in human plasma and this protein's putative role as a plasma-based loading control for Western blot analysis remain unknown. In this study, an enzyme-linked immunosorbent assay was used to determine the concentration of β-actin in human plasma, which is 6.29±0.54 ng/ml. In addition, the linearity of β-actin immunostaining and loaded protein amount was evaluated by Western blot, and a fine linearity (R2=0.974±0.012) was observed. Furthermore, the expression of plasma β-actin in major depressive disorder subjects and healthy controls was compared. The data revealed no statistically significant difference between these two groups. Moreover, the total coefficient of variation for β-actin expression in the two groups was 9.2±1.2%. These findings demonstrate that β-actin is present in human plasma and may possibly be used as a suitable loading control for plasma-based Western blot analysis in major depressive disorder. 相似文献