Anti-tumor effects of combined doxorubicin and siRNA for pulmonary delivery

Direct administration of drugs and genes to the lungs by pulmonary delivery offers a potential effective therapy for lung cancers.In this study,combined doxorubicin(DOX)and Bcl2 siRNA was employed for cancer therapy using polyethylenimine(PEI)as the carrier of Bcl2 siRNA.Most of the DOX and siRNA possessed high cellular uptake efficiency in B16F10 cells,which was proved by FCM and CLSM analysis. Real-time PCR showed that PEI/Bcl2 siRNA exhibited high gene silencing efficiency with 70% Bcl2 mRNA being knocked down.The combination of DOX and siRNA could enhance the cell proliferation inhibition and the cell apoptosis against B16F10 cells compared to free DOX or PEI/Bcl2 siRNA.Furthermore,the biodistribution of DOX and siRNA via pulmonary administration was studied in mice with B16F10 metastatic lung cancer.The results showed that most of the DOX and siRNA were accumulated in lungs and lasted at least for 3 days,which suggested that combined DOX and siRNA by pulmonary administration may have high anti-tumor effects for metastatic lung cancer treatment in vivo.     

Searching for gallium bioactive compounds: Gallium(III) complexes of tridentate salicylaldehyde semicarbazone derivatives

In the search for gallium bioactive compounds five Ga(III) complexes, [Ga^III(L-H)₂](NO₃), with tridentate salicylaldehyde semicarbazone derivatives as ligands (L) have been synthesized and characterized in the solid state and in solution by different techniques. The crystal structure of [Ga^III(L4-H)₂](NO₃)·2H₂O, where L4 is 3-ethoxysalicylaldehyde semicarbazone, was solved by X-ray diffraction methods. The gallium(III) ion is in a distorted octahedral environment, coordinated to two nearly planar and mutually perpendicular 3-ethoxysalicylaldehyde semicarbazonato anions acting as tridentate ligands through their phenol and carbonyl oxygen atoms and their azomethine nitrogen atom. Their biological potential has been explored by evaluating their activity on Mycobacterium tuberculosis, causative agent of tuberculosis, and their cytotoxicity on tumor cell lines. Three different human tumor cell lines were selected that show different degrees of resistance to metallodrugs: ovarian A2780 (low resistance), breast MCF7 (medium resistance) and prostate PC3 (high resistance) cells. Although the complexes have not shown activity on M. tuberculosis, complexation with gallium has led to the enhancement of the cytotoxic potencies of the organic compounds. Those complexes that contain a bromide substituent at the phenolate ring have shown the highest cytotoxicities. In particular, [Ga^III(L2-H)₂](NO₃), where L2 is 5-bromosalicylaldehyde semicarbazone,·has shown a remarkable cytotoxicity on A2780 tumor cell line with an IC₅₀ value of the same order than cisplatin (IC_{50 Ga-L2} = 2.4 ± 0.3 μM; IC_{50 cisplatin} = 2.0 ± 0.1 μM, 72 h incubation at 37 °C). Interestingly, this complex has also shown moderate cytotoxicity against MCF7 and PC3 cells (IC_{50 MCF7} = 30 ± 6; IC_{50 PC3} = 18 ± 3 μM). Therefore, this gallium compound could be considered a promising wide spectrum potential anti-tumor agent.     

A convenient synthesis of the enantiomerically pure (S)-2,4-dihydroxybutyl-4-hydroxybenzoate using hydrolytic kinetic resolution

(S)-2,4-Dihydroxybutyl-4-hydroxybenzoate was prepared in an extremely simple and practical way with high enantiomeric excess (99% ee) using Jacobsen’s Hydrolytic Kinetic Resolution technique as a key step and source of chirality.     

Synthesis and biological evaluation of novel thalidomide analogues as potential anticancer drugs

In search of novel anticancer agents, a series of thalidomide analogs （6a-j） were designed and synthesized. Cytotoxicity of these compounds against human hepatoma cells （HepG2） was evaluated by MTT method. Compounds 6d, 6h and 6i showed significant cytotoxic activities comparable to or stronger than control 5-fluorouracil.     

Synthesis, Structure Characterization and Biological Activity of a Novel Polyoxovanadate Cluster: [NH3(CH2)2NH2(CH2)2NH3]4·[VⅤ6VⅣ12O42(PO4)](PO4)·2H2O

A new polyoxovanadate cluster,[NH3(CH2)2NH2(CH2)2NH3]4[VⅤ6VⅣ12O42(PO4)](PO4)·2H2O, has been synthesized and characterized by means of elemental analysis, IR spectrometry, EPR spectrometry, TG analysis and single crystal X-ray diffraction. This compound crystallizes in a monoclinic space group C2/c with a=2.3912(5) nm, b=1.3002(3) nm, c=2.0172(4) nm, β=105.75(3)°, V=6.036(2) nm3, Z=2, R1=0.0572, wR2=0.1476. It has a superKeggin structure with a Keggin unit capped by six [VO5] moieties on the pits on every side of the Keggin unit. The anti-tumor activity of the compound was estimated in three human tumor cell lines in vitro.     

糖类研究(ⅩⅩⅪ)带连接臂的乳糖衍生物及二聚体的合成

八乙酰乳糖与一缩二乙二醇或二缩三乙二醇在 BF3.Et2 O催化下反应生成相应的 β-糖苷 ,后者在同样的催化剂存在下再与八乙酰乳糖反应生成对称的 β-构型二聚体 .糖苷与二聚体在甲醇钠 /甲醇溶液中脱去乙酰基生成目标化合物用于抗癌转移活性研究 .     

Synthesis, Structure Characterization and Biological Activity of a Novel Polyoxovanadate Cluster: [NH_3(CH_2)_2NH_2(CH_2)_2NH_3]_4·[V_6~Ⅴ V_(12)~Ⅳ O_(42)(PO_4)](PO_4)·2H_2O

IntroductionPolyoxometalates(POMs)have been attracting ex-tensive interest in solid state material chemistry due tothe richness of their structures and special properties incatalysis,photochemistry,electro-chromism and mag-netism[1—3].POMs have also attracted increasing inter-est of biochemists because of their potential applicationsas drugs againsttumors and viruses[4—6].Agood way todesign drugs based on POMs is to modify the polyox-oanion frameworks with appropriate chemicals,such asami…     

The critical phenomenon and the re-entrance phenomenon in the anti-tumor model induced by the time delay

The effects of time delay τ on an anti-tumor model driven by a multiplicative noise and a periodic signal are investigated. The results obtained from the small delay approximation and numerical simulations indicate: (i) For the absence of the periodic signal in the system, the two-peak structure of the stationary probability distribution transforms into the single-peak structure with the increasing τ, and τ exists a critical value τc. For τ<τc, the stationary mean value 〈x〉_st of the cell population decreases as the noise intensity D increases, however, for τ>τc, the 〈x〉_st increases as the D increases; (ii) For the presence of the periodic signal in the system, the structure of the signal-to-noise ratio with changes of the D exhibits the transitions of one peak → two peaks → one peak as τ increases.     

氟尿嘧啶-壳寡糖/硒纳米微球的制备及抑制肿瘤细胞生长活性

为研究抗肿瘤药物与辅药负载于同一药物载体的作用效果, 首先以壳寡糖和广谱抗肿瘤药物5-氟尿嘧啶(5-Fu)为原料通过化学键合合成氟尿嘧啶-壳寡糖前体, 然后以其为模板通过溶胶-凝胶法制备了同时负载氟尿嘧啶和硒纳米颗粒的壳寡糖微球. 采用透射电子显微镜(TEM)、 Zeta电位仪和红外光谱(IR)对制备的微球进行了表征, 结果表明, 微球粒径为433 nm, 硒纳米颗粒包裹在微球内; 对微球包裹药物进行检测发现, 5-Fu装载率为(8.2±0.3)%, 硒装载率为(7.96±0.34)%; 体外缓释检测和细胞实验结果证实, 微球能够缓慢释放2种药物, 其缓释作用能很好地抑制肝癌细胞SMMC-7721的生长.     

Synthesis, Structure Characterization and Biological Activity of Adenine Salt of 12-Phosphotungstic Acid

IntroductionOwingtothegreatpotentialoftheapplicationsofpolyoxometalatesasdrugsagainsttumorsandviruses ,theircomplexeshaveattractedanincreasinginterestofbothinorganicchemistsandbiochemists[1,2 ] .Inthelastfewyears ,thenumberofreportsinthelitera tureaddressingtheuseofpolyoxometalatesasantivi ralandanti tumoragents[3— 5] mounteduprapidly .However ,many polyoxometalatestestedshowtheloweractivityinvivothanthatinvitro .Inordertoimprovetheefficacyofthedrugs ,itisconsideredtomodifythepolyoxoanionfram…