Publications (45)106.47 Total impact
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Article: Theoretical study on the degradation of ADP-ribose polymer catalyzed by poly(ADP-ribose) glycohydrolase.
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ABSTRACT: Poly(ADP-ribose) glycohydrolase (PARG) is the only enzyme responsible for the degradation of ADP-ribose polymers. Very recently, the first crystal structure of PARG was reported (Dea Slade, et al., Nature 477 (2011) 616), and a possible SN1-type-like mechanism was proposed. In this work, we present a computational study on the hydrolysis of glycosidic ribose-ribose bond catalyzed by PARG using hybrid density functional theory (DFT) methods. Based on the crystal structure of PARG, three models of the active site were constructed. The calculation results suggest that the degradation of poly(ADP-ribose) follows an SN2 mechanism, and the oxocarbenium expected by Dea Slade is a possible transition state but not an intermediate. The calculated reaction pathway agrees with the proposed mechanism. According to the computational models with different sizes, the roles of key residues are elucidated. Our results may provide useful information for the subsequent experimental and theoretical studies on the structure and functional relationships of PARG.Journal of molecular graphics & modelling 03/2013; 42C:26-31. · 2.17 Impact Factor -
Article: Metal vs. chalcogen competition in the catalytic mechanism of cysteine dioxygenase.
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ABSTRACT: Why the cysteine dioxygenase (CDO) cannot catalyze the oxidation of selenocysteine (Sec) but that of cysteine (Cys) is still an open question. In order to solve this question, the CDO model complex, the active site of CDO, and their selenium-substituted complexes have been selected as the computational models in this work. The stepwise donation of electron density during the first two reaction steps has been explored. In the first step, the electron density-donor ability of Se to donate to Fe is stronger than that of S; in the second step, S has the better electron density-donor ability to donate to O(2) than Se. Under the influence, in the Cys-bound complexes, the change of the oxidation state for the Fe center is II→III→II, while the Fe center in the Sec-bound complexes remains in the II oxidation state throughout. Considering that the ferric-superoxo species is an active oxidant and exhibits high reactivity in such reaction, it is speculated that the valence change of the Fe center makes the Cys-bound complexes effectively catalyze the oxidation of Cys, while the Sec-bound complexes cannot catalyze the oxidation of Sec. The competition for donation of electron density determines the valence change and the reaction ability.Journal of inorganic biochemistry 01/2013; 122C:1-7. · 3.25 Impact Factor -
Article: Mechanistic investigations of Al(OH)(3) oligomerization mechanisms.
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ABSTRACT: Aluminum aerogels have extremely low thermal conductivities, and are ideal candidates for use in thermal superinsulators, adsorbents, sensors, catalyst carriers, and inorganic fillers. In the present work, the oligomerization mechanisms of Al(OH)(3) were investigated systematically with the Gaussian 03 package at the B3LYP/6-311++G(d,p) level in combination with CPCM single-point energy calculations. The results of our theoretical model showed that: (1) the Al atoms are tetracoordinate and pentacoordinate; (2) in alkaline solution, Al(OH)(3) tends to condense into more soluble polyhydroxy compounds; (3) the neutral dimerization of Al(OH)(3) and the transfer of the hydrogen on the bridging hydroxyl are energetically favorable, but the most stable geometry is a four-membered Al-O ring structure linked by two bridging hydroxyls; (4) Al(OH)(3) is inclined to form tetracoordinate oligomers, which develop into three-dimensional structures connected by four-membered Al-O rings.Journal of Molecular Modeling 12/2012; · 1.80 Impact Factor -
Article: X-ray crystallography and QM/MM investigation on the oligosaccharide synthesis mechanism of rice BGlu1 glycosynthases.
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ABSTRACT: Nucleophile mutants of retaining β-glycosidase can act as glycosynthases to efficiently catalyze the synthesis of oligosaccharides. Previous studies proved that rice BGlu1 mutants E386G, E386S and E386A catalyze the oligosaccharide synthesis with different rates. The E386G mutant gave the fastest transglucosylation rate, which was approximately 3- and 19-fold faster than those of E386S and E386A. To account for the differences of their activities, in this paper, the X-ray crystal structures of BGlu1 mutants E386S and E386A were solved and compared with that of E386G mutant. However, they show quite similar active sites, which implies that their activities can not be elucidated from the crystal structures alone. Therefore, a combined quantum mechanical/molecular mechanical (QM/MM) calculations were further performed. Our calculations reveal that the catalytic reaction follows a single-step mechanism, i.e., the extraction of proton by the acid/base, E176, and the formation of glycosidic bond are concerted. The energy barriers are calculated to be 19.9, 21.5 and 21.9kcal/mol for the mutants of E386G, E386S and E386A, respectively, which is consistent with the order of their experimental relative activities. But based on the calculated activation energies, 1.1kcal/mol energy difference may translate to nearly 100 fold rate difference. Although the rate limiting step in these mutants has not been established, considering the size of the product and the nature of the active site, it is likely that the product release, rather than chemistry, is rate limiting in these oligosaccharides synthesis catalyzed by BGlu1 mutants.Biochimica et Biophysica Acta 11/2012; · 4.66 Impact Factor -
Article: Theoretical studies on the common catalytic mechanism of transketolase by using simplified models.
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ABSTRACT: Transketolase is a convenient model system to study enzymatic thiamin catalysis. By using density functional theory (DFT) method, the transfer mechanism of a 2-carbon fragment between a donor ketose X5P and an acceptor aldose R5P catalyzed by transketolase has been studied on simplified models. The calculation results indicate that the whole reaction cycle contains several proton transfer processes as well as CC bond formation and cleavage steps. Each CC bond formation or cleavage step is always accompanied by a proton transfer process, which follows a concerted but asynchronous mechanism. The CC bond formation is always prior to the proton transfer, and the CC bond cleavage is always later than proton transfer, suggesting that the CC bond ligation facilitates the proton transfer, and proton transfer promotes the CC bond cleavage. In the first half- and second half-reactions, the energy barriers of CC bond formations are always higher than those of CC bond cleavages. The 4-amino group of cofactor ThDP and histidine residue can act as the proton donor/acceptor during the catalytic reaction.Journal of molecular graphics & modelling 11/2012; 39C:23-28. · 2.17 Impact Factor -
Article: Biodegradable solid lipid nanoparticle flocculates for pulmonary delivery of insulin.
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ABSTRACT: The aim of our study was to prepare and characterize biodegradable insulin-loaded solid lipid nanoparticles (Ins-SLNs) flocculates for the pulmonary delivery of Ins. The cationic Ins-SLNs and anionic Ins-SLNs were prepared by W/O/W emulsion technique, respectively. Then anionic Ins-SLNs were self-assembled into flocculates via electrostatic interactions with the oppositely surface charged cationic Ins-SLNs followed by lyophilized into dry powders. The maximal entrapment efficiency of cationic Ins-SLNs and anionic Ins-SLNs were 56.32 +/- 1.01% and 66.02 +/- 1.58%, respectively. Freeze-drying the Ins-SLNs flocculates yielded dry powders with desirable aerodynamic diameter of 2.04 +/- 0.17 microm and low bulk density of 0.06146 +/- 0.0045 g/cm3, suitable for inhalation. In addition, the flocculates showed high aerosolization efficiency (emitted fraction of 92.54 +/- 0.77% and respirable fraction of 66.89 +/- 3.02%). The in vivo study showed that Ins-SLNs flocculates could prolong hypoglycemic effect and a relative pharmacological bioavailability of 35.62 +/- 1.34% could be achieved after intratracheal instillation to diabetic rats at the dose of 8 IU/kg dosage. Therefore, the biodegradable SLN flocculates fabricated via charge interaction may provide a useful strategy to fabricate dry powder for pulmonary administration of protein therapeutics or antigens.Journal of Biomedical Nanotechnology 10/2012; 8(5):834-42. · 4.22 Impact Factor -
Article: Water-Dependent Reaction Pathways: An Essential Factor for the Catalysis in HEPD Enzyme.
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ABSTRACT: The hydroxyethylphosphonate dioxygenase (HEPD) catalyzes the critical carbon-carbon bond cleavage step in the phosphinothricin (PT) biosynthetic pathway. The experimental research suggests that water molecules play an important role in the catalytic reaction process of HEPD. This work proposes a water involved reaction mechanism where water molecules serve as an oxygen source in the generation of mononuclear nonheme iron oxo complexes. These molecules can take part in the catalytic cycle before the carbon-carbon bond cleavage process. The properties of trapped water molecules are also discussed. Meanwhile, water molecules seem to be responsible for converting the reactive hydroxyl radical group ((-)OH) to the ferric hydroxide (Fe(III)-OH) in a specific way. This converting reaction may prevent the enzyme from damages caused by the hydroxyl radical groups. So, water molecules may serve as biological catalysts just like the work in the heme enzyme P450 StaP. This work could provide a better interpretation on how the intermediates interact with water molecules and a further understanding on the O(18) label experimental evidence in which only a relatively smaller ratio of oxygen atoms in water molecules (∼40%) are incorporated into the final product HMP.The Journal of Physical Chemistry B 09/2012; 116(39):11837-44. · 3.70 Impact Factor -
Article: Molecular dynamics simulation of the interaction between protein tyrosine phosphatase 1B and aryl diketoacid derivatives.
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ABSTRACT: The protein tyrosine phosphatase 1B (PTP-1B) is acknowledged as an outstanding therapeutic target for the treatment of diabetes, obesity and cancer. In this work, six aryl diketoacid compounds have been studied on the basis of molecular dynamics simulations. Hydrogen bonds, binding energies and conformation changes of the WPD loop have been analyzed. The results indicated that their activation model falls into two parts: the target region of the monomeric aryl diketoacid compounds is the active site, whereas the target region of the dimeric aryl diketoacid compounds is the WPD loop or the R loop. The van der Waals interactions exhibit stronger effects than the short-range electrostatic interactions. The van der Waals interaction energy and the IC50 values exhibit an approximately exponential relationship. Furthermore, the van der Waals interactions cooperate with the hydrogen bond interactions. This study provides a more thorough understanding of the PTP-1B inhibitor binding processes.Journal of molecular graphics & modelling 07/2012; 38C:186-193. · 2.17 Impact Factor -
Article: [Preparative separation of two xanthones from Halenia elliptica by high-speed counter-current chromatography].
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ABSTRACT: A high performance method for isolation and purification of two xanthones from a crude extract of Halenia elliptica was successfully established by utilizing high-speed countercurrent chromatography (HSCCC). The separation was performed with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (5:5:7:5, v/v/v/v) with the lower phase as the mobile phase at a flow rate of 1.5 mL/min. The apparatus was rotated at 800 r/min. The effluent was detected at 254 nm. Under the optimized conditions, 18 mg of 1-hydroxy-2,3, 5-trimethoxyxanthone and 14 mg of 1-hydroxy-2,3,4,5-tetramethoxyxanthone were obtained from 100 mg of the crude extract of Halenia elliptica in one-step separation within 360 min. The results of high performance liquid chromatographic (HPLC) analysis showed that the purity of each of the target compounds was over 98%. The chemical structures of the two compounds were confirmed by 1H nuclear magnetic resonance (1H NMR) and 13C NMR. The established method is simple, highly efficient and suitable for large scale separation of xanthones from Halenia elliptica.Se pu = Chinese journal of chromatography / Zhongguo hua xue hui 05/2012; 30(5):543-6. -
Article: Mechanisms of silicon alkoxide hydrolysis-oligomerization reactions: a DFT investigation.
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ABSTRACT: Silica aerogels possess a variety of unique and remarkable properties, but the mechanisms of silicon alkoxide, Si(OR)(4), hydrolyses and oligomerization in the initial stage of sol-gel processes are still not well understood. On the basis of density functional theory calculations at the B3LYP/6-31G(d,p)//B3LYP/6-311++G(d,p) basis set level, the hydrolysis and oligomerization reactions of Si(OR)(4) in neutral, acidic, and alkaline solutions were systematically investigated and we found that in acidic solutions the precursor Si(OCH(3))(4) was inclined to hydrolyze rather than to condense and the hydrolysis processes were energetically more favorable than the neutral ones. In alkaline solutions, the hydrolysis products oligomerize through an S(N)1 dimerization mechanism and the condensation rates are fast to form denser colloidal aerogels. Our calculations also testify that the subsequent cyclization reactions are energetically unfavorable.ChemPhysChem 04/2012; 13(9):2392-404. · 3.41 Impact Factor -
Article: Gadolinium loaded nanoparticles in theranostic magnetic resonance imaging.
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ABSTRACT: Theranostic magnetic resonance imaging (MRI) is now receiving a growing interest in imaging-guided drug delivery, monitoring the treatment and personalized administration etc. Theranostic agents are essential for the usage of theranostic MRI. Among different kinds of theranostic agents, gadolinium loaded nanoparticles (GdNPs) are one of the most promising theranostic agents which are very promising in combination of diagnostics (molecular imaging) and therapeutics (molecular therapy) functions in a single platform. In this review, we provided fully discussion on the design considerations of GdNPs as a platform for theranostic MRI. The mainly factors that affect the preparation process, such as GdNP materials, the loading of Gd/drugs in GdNPs, and the passive and active targeting strategies were discussed. Major classes of GdNPs including lipid-based nanoparticles, polymeric nanoparticles, micelles, dendrimers and Gd-silica nanoparticles were described in detail. The use of GdNPs as theranostic agents offers potential advantages that change the usual cancer therapy from separating diagnosis and treatment to theranostic approach.Biomaterials 04/2012; 33(21):5363-75. · 7.40 Impact Factor -
Article: QM/MM investigation on the catalytic mechanism of Bacteroides thetaiotaomicron α-glucosidase BtGH97a.
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ABSTRACT: Bacteroides thetaiotaomicron α-glucosidase BtGH97a is an inverting enzyme. In this paper, the hydrolysis mechanism of p-nitro-phenyl α-d-glucopyranoside (pNP-Glc) catalyzed by BtGH97a was firstly studied by using quantum mechanical/molecular mechanical (QM/MM) approach. Two possible reaction pathways were considered. In the first pathway, a water molecule deprotonated by a nucleophilic base (here E439 or E508) attacks firstly on the anomeric carbon of pNP-Glc, then a proton from an acid residue (E532) attacks on the glycosidic oxygen to finish the hydrolysis reaction (named as nucleophilic attack-first pathway). In the second pathway, the proton from E532 attacks firstly on the glycosidic oxygen, then the water deprotonated by the nucleophilic base attacks on the anomeric carbon of pNP-Glc (named as proton attack-first pathway). Our calculation results indicate that the nucleophilic attack-first pathway is favorable in energy, in which the nucleophilic attack process is the rate-determining step with an energy barrier of 15.4kcal/mol in the case of residue E508 as nucleophilic base. In this rate-determining step, the deprotonation of water and the attack on the anomeric carbon are concerted. In the proton attack-first pathway, the proton attack on the glycosidic oxygen is the rate-determining step, and the energy barrier is 24.1kcal/mol. We conclude that the hydrolysis mechanism would follow nucleophilic attack-first pathway.Biochimica et Biophysica Acta 03/2012; 1824(5):750-8. · 4.66 Impact Factor -
Article: Theoretical studies on the interaction of biphenyl inhibitors with Mycobacterium tuberculosis protein tyrosine phosphatase MptpB.
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ABSTRACT: MptpB is an essential secreted virulence factor for M. tuberculosis. Inhibition of MptpB impairs mycobacterial survival in host macrophages and thus helps reduce tuberculosis infections. However, the binding mode of the biphenyl inhibitors, which are known as some of the most potent MptpB inhibitors, remains unclear. In this study, to understand the interactions between biphenyl inhibitors and MptpB, docking and molecular dynamics simulations were carried out using AutoDock and GROMACS softwares. Calculation results show that all the biphenyl inhibitors can be docked to the binding site of MptpB, with the acid warheads forming a hydrogen bond network at the active site. But the binding modes of other terminals of these inhibitors are different. The cyclohexyl and trifluoromethyl substituents at R1 and R2 sites are necessary for the inhibitors to adopt their double-site binding mechanism. The estimated binding affinities are basically consistent with the experimental results. MD simulations show that these binding complexes display different stability.Journal of Molecular Modeling 03/2012; 18(8):3847-56. · 1.80 Impact Factor -
Article: Molecular dynamics simulations of the coenzyme induced conformational changes of Mycobacterium tuberculosis L-alanine dehydrogenase.
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ABSTRACT: Mycobacterium tuberculosis L-alanine dehydrogenase (L-MtAlaDH) catalyzes the NADH-dependent reversible oxidative deamination of L-alanine to pyruvate and ammonia. L-MtAlaDH has been proposed to be a potential target in the treatment of tuberculosis. Based on the crystal structures of this enzyme, molecular dynamics simulations were performed to investigate the conformational changes of L-MtAlaDH induced by coenzyme NADH. The results show that the presence of NADH in the binding domain restricts the motions and conformational distributions of L-MtAlaDH. There are two loops (residues 94-99 and 238-251) playing important roles for the binding of NADH, while another loop (residues 267-293) is responsible for the binding of substrate. The opening/closing and twisting motions of two domains are closely related to the conformational changes of L-MtAlaDH induced by NADH.Journal of molecular graphics & modelling 02/2012; 35:1-10. · 2.17 Impact Factor -
Article: A pH-sensitive multifunctional gene carrier assembled via layer-by-layer technique for efficient gene delivery.
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ABSTRACT: The success of gene therapy asks for the development of multifunctional vectors that could overcome various gene delivery barriers, such as the cell membrane, endosomal membrane, and nuclear membrane. Layer-by-layer technique is an efficient method with easy operation which can be used for the assembly of multifunctional gene carriers. This work describes a pH-sensitive multifunctional gene vector that offered long circulation property but avoided the inhibition of tumor cellular uptake of gene carriers associated with the use of polyethylene glycol. Deoxyribonucleic acid (DNA) was firstly condensed with protamine into a cationic core which was used as assembly template. Then, additional layers of anionic DNA, cationic liposomes, and o-carboxymethyl-chitosan (CMCS) were alternately adsorbed onto the template via layer-by-layer technique and finally the multifunctional vector called CMCS-cationic liposome-coated DNA/protamine/DNA complexes (CLDPD) was constructed. For in vitro test, the cytotoxicity and transfection investigation was carried out on HepG2 cell line. For in vivo evaluation, CMCS-CLDPD was intratumorally injected into tumor-bearing mice and the tumor cells were isolated for fluorescence determination of transfection efficiency. CMCS-CLDPD had ellipsoidal shapes and showed "core-shell" structure which showed stabilization property in serum and effective protection of DNA from nuclease degradation. In vitro and in vivo transfection results demonstrated that CMCS-CLDPD had pH-sensitivity and the outermost layer of CMCS fell off in the tumor tissue, which could not only protect CMCS- CLDPD from serum interaction but also enhance gene transfection efficiency. These results demonstrated that multifunctional CMCS-CLDPD had pH- sensitivity, which may provide a new approach for the antitumor gene delivery.International Journal of Nanomedicine 01/2012; 7:925-39. · 3.13 Impact Factor -
Article: The reaction mechanism of hydroxyethylphosphonate dioxygenase: a QM/MM study.
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ABSTRACT: By employing ab initio quantum mechanical/molecular mechanical (QM/MM) and molecular dynamics (MD) simulations, we have provided further evidence against the previously proposed hydroperoxylation or hydroxylation mechanism of hydroxyethylphosphonate dioxygenase (HEPD). HEPD employs an interesting catalytic cycle based on concatenated bifurcations. The first bifurcation is based on the abstraction of hydrogen atoms from the substrate, which leads to a distal or proximal hydroperoxo species (Fe-OOH or Fe-(OH)O). The second and the third bifurcations refer to the carbon-carbon bond cleavage reaction. And this is achieved through a tridentate intermediate, or employing a proton-shuttle assisted mechanism, in which the residue Glu(176) or the Fe(IV)=O group serves as a general base. The reaction directions seem to be tunable and show significant environment dependence. This mechanism can provide a comprehensive interpretation for the seemingly contradicting experimental evidences and provide insight into the development of biochemistry and material sciences.Organic & Biomolecular Chemistry 12/2011; 10(5):1014-24. · 3.70 Impact Factor -
Article: Preparative separation of methylswertianin, swerchirin and decussatin from the Tibetan medicinal plant Swertia mussotii using high-speed counter-current chromatography.
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ABSTRACT: Xanthones, the primary constituents of Swertia mussotii, are known to possess a variety of biological activities, including anti-depressant, anti-leukaemic, anti-tumour, anti-tubercular, choleretic, diuretic, anti-microbial, anti-fungal, anti-inflammatory, anti-viral, cardiotonic and hypoglycemic properties. However, high performance, environmentally friendly methods for isolating and purifying xanthones from S. mussotii are not currently available. To develop a high performance and environmentally friendly method for the preparative separation of xanthones methylswertianin, swerchirin and decussatin from S. mussotii using high-speed counter-current chromatography (HSCCC). A solvent system composed of n-hexane:ethyl acatate:methanol:water (5:5:10:4, v/v/v/v) was developed for the separation method. The upper phase was used as the stationary phase, and the lower phase was used as the mobile phase at a flow rate of 1.5 mL/min, a rotation speed of 800 rpm and a temperature of 25 °C. Using the described method, 8 mg of methylswertianin, 21 mg of swerchirin and 11 mg of decussatin with purities of over 98% could be isolated from a 150 mg crude sample. They were identified by ¹H-NMR and ¹³C-NMR analysis. Three xanthones in Swertia mussotii could be systematically isolated and purified using HSCCC.Phytochemical Analysis 11/2011; 23(4):332-6. · 2.63 Impact Factor -
Article: Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer.
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ABSTRACT: Molecular imaging is essential to increase the sensitivity and selectivity of cancer diagnosis especially in the early stage of tumor. Here, we designed a novel multifunctional polymeric nanoparticle contrast agent (Anti-VEGF PLA-PEG-PLL-Gd NP) simultaneously modified with Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and anti-vascular endothelial growth factor (VEGF) antibody to deliver Gd-DTPA to the tumor area and achieve the early diagnosis of hepatocellular carcinoma (HCC). The Anti-VEGF PLA-PEG-PLL-Gd NPs exhibited high T(1) relaxivity and no obvious cytotoxicity under the experimental concentrations in human hepatocellular carcinoma (HepG2) cells. The results of in vitro cell uptake experiments demonstrated that the uptake process of NPs was both concentration and time depended. Compared with non-targeted NPs, the Anti-VEGF antibody modified NPs showed much higher cell uptake in the HepG2 cells. During in vivo studies, the targeted NPs showed significantly signal intensity enhancement at the tumor site (mouse hepatocarcinoma tumor, H22) compared with non-targeted NPs and Gd-DTPA injection in tumor-bearing mice and the imaging time was significantly prolonged from less than an hour (Gd-DTPA injection group) to 12 h. These results demonstrated that this novel MRI contrast agent Anti-VEGF PLA-PEG-PLL-Gd NPs showed great potential in the early diagnosis of liver tumors.Biomaterials 08/2011; 32(22):5167-76. · 7.40 Impact Factor -
Article: QM/MM studies on the glycosylation mechanism of rice BGlu1 β-glucosidase.
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ABSTRACT: The quantum-mechanical/molecular-mechanical (QM/MM) method was used to study the glycosylation mechanism of rice BGlu1 β-glucosidase in complex with laminaribiose. The calculation results reveal that the glycosylation step experiences a concerted process from the reactant to the glycosyl-enzyme complex with an activation barrier of 15.7 kcal/mol, in which an oxocarbenium cation-like transition state (TS) is formed. At the TS, the terminal saccharide residue planarizes toward the half-chair conformation, and the glycosidic bond cleavage is promoted by the attacks of proton donor (E176) on glycosidic oxygen and nucleophilic residue (E386) on the anomeric carbon of laminaribiose. Both the nucleophilic glutamate (E386) and acid/base catalyst (E176) establish shorter hydrogen bridges with the C₂-hydroxyl groups of sugar ring, which play an important role in the catalytic reaction of rice BGlu1 β-glucosidase.Journal of molecular graphics & modelling 07/2011; 30:148-52. · 2.17 Impact Factor -
Article: A novel cationic liposome formulation for efficient gene delivery via a pulmonary route.
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ABSTRACT: The clinical success of gene therapy for lung cancer is not only dependent on efficient gene carriers but also on a suitable delivery route. A pulmonary delivery route can directly deliver gene vectors to the lung which is more efficient than a systemic delivery route. For gene carriers, cationic liposomes have recently emerged as leading non-viral vectors in worldwide gene therapy clinical trials. However, cytotoxic effects or apoptosis are often observed which is mostly dependent on the cationic lipid used. Therefore, an efficient and safe cationic lipid, 6-lauroxyhexyl lysinate (LHLN), previously synthesized by our group was first used to prepare cationic liposomes. Physicochemical and biological properties of LHLN-liposomes were investigated. LHLN-liposome/DNA complexes showed positive surface charge, spherical morphology, a relatively narrow particle size distribution and strong DNA binding capability. Compared with Lipofectamine2000, the new cationic liposome formulation using LHLN exhibited not only lower cytotoxicity (P < 0.05) but also similar transfection efficiency in A549 and HepG2 lung cancer cells for in vitro tests. When administered by intratracheal instillation into rat lungs for in vivo evaluation, LHLN-liposome/DNA complexes exhibited higher pulmonary gene transfection efficiency than Lipofectamine2000/DNA complexes (P < 0.05). These results suggested that LHLN-liposomes may have great potential for efficient pulmonary gene delivery.Nanotechnology 06/2011; 22(24):245104. · 3.98 Impact Factor
Top co-authors
Top Journals
Institutions
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2006–2013
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Shandong University
- • Key Laboratory for Colloid and Interface Chemistry
- • School of Pharmaceutical Sciences
- • Department of Chemical Engineering
Jinan, Shandong Sheng, China
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2011–2012
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Chinese Academy of Sciences
Beijing, Beijing Shi, China
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2000–2012
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Qufu Normal University
Qufu, Shandong Sheng, China
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2007–2009
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Northwest Institute of Plateau Biology
Xining, Qinghai Sheng, China
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2008
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University of Chinese Academy of Sciences
Beijing, Beijing Shi, China
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