肝靶向纳米给药系统的最新研究进展

肝脏疾病是威胁人类生命健康的重要疾病之一,对肝脏疾病检测及治疗方法的研究也引起人们的极大重视。靶向药物递送系统(TDDS)可将药物选择性地输送到靶点组织,从而提高药物的生物利用率并降低毒副作用,已引起了研究者的广泛关注。近年来,越来越多的研究尝试将靶向药物递送系统应用于肝脏疾病的显像检测以及药物/基因治疗,并取得了十分显著的成绩。本文将对近年来开发的新型纳米肝靶向给药系统,尤其是配体-受体介导的主动肝靶向给药系统在药物/基因递送以及显影检测方面的最新进展做一个综述,对各靶向给药系统的肝靶向能力进行了总结对比,并对肝靶向给药系统的发展方向进行了预测。     

多肽介导的肿瘤靶向纳米递药系统

肿瘤靶向纳米递药系统是指利用肿瘤组织特殊的生理病理特点,由纳米载体包载肿瘤诊疗药物构建而成的对肿瘤组织具有靶向定位功能的药物递送系统。多肽介导的肿瘤靶向纳米递药系统是肿瘤靶向递药领域较新的一个研究方向,本文综述了该研究方向的四个重要发展历程——单功能靶向、双功能靶向、肿瘤穿透和环境响应型靶向纳米递药系统,并介绍了各类递药系统的设计原理和典型研究案例。此外,对目前多肽介导的纳米递药系统存在的优势与不足进行了分析。最后,针对当前主动靶向肿瘤递药系统存在的研究困境,提出了一种新型肿瘤靶向递药策略——"系统性靶向"策略。随着相关学科和多学科交叉的发展,多肽介导的肿瘤靶向纳米递药系统将在肿瘤治疗中扮演更为重要的角色。     

磁性壳聚糖微球的制备、表征及其靶向给药研究

磁性微球;阿司匹林;磁性壳聚糖微球的制备、表征及其靶向给药研究     

基于环糊精的靶向药物传递系统

癌症等恶性增殖疾病的靶向治疗有赖于靶向药物传递系统（targeted drug delivery system,TDDS）的开发。环糊精具有低毒、易修饰等优良性质,并可通过与药物分子形成包合物而提高药物的溶解性、稳定性、安全性和生物利用度等,因而具有成为优秀药物载体的潜力。环糊精不仅可以以其本身或修饰环糊精的形式充当载体,还可通过聚轮烷、阳离子聚合物或纳米粒等形式构建有效的药物载体。肿瘤或人体某些病变部位的细胞表面存在过度表达的生物受体如叶酸受体、去唾液酸糖蛋白受体、透明质酸受体、转铁蛋白受体和整合素受体等,可以与其相应的配体产生特异性识别。用适当的化学方法将配体分子如叶酸、单糖或寡糖、透明质酸、转铁蛋白及RGD肽等键接在基于环糊精的载体上,可形成具有靶向性质的药物载体,进而与药物分子一起构筑靶向药物传递系统。这种药物传递系统不仅针对于化学治疗药物,在核酸传递中也得到了丰富的应用。本文综述了基于环糊精的靶向药物传递系统的靶向机理及最新研究进展,并对其发展前景作了展望。     

基于透明质酸的刺激响应纳米给药系统的研究进展

透明质酸(Hyaluronic acid, HA)是一种天然多糖,具有良好的生物相容性和生物降解性,利用 HA 构建的纳米载体自身就具有肿瘤靶向功能,可以作为抗癌药物载体将药物传递到肿瘤细胞内从而实现精准到达病患处。近年来透明质酸在应用于肿瘤靶向给药系统中的关注越来越多,成为了靶向治疗肿瘤的一大研究热点。基于透明质酸的基本特性和肿瘤靶向的生理学基础,在不同的刺激响应下,透明质酸型纳米给药系统能将药物集中释放于肿瘤的微环境内,更好地杀死肿瘤细胞,同时避免其他正常的组织受到药物损害。本文主要综述了透明质酸型纳米药物输送系统在各种刺激响应下释放药物的最新研究进展。     

肝靶向甘草次酸修饰的壳聚糖纳米粒子的合成和表征

合成了修饰甘草次酸的壳聚糖(GA-CTS), 采用离子交联法制备了GA-CTS纳米粒子. 该材料可能具有肝细胞主动靶向作用, 为进一步的肝靶向药物控释的研究奠定了基础.     

基于单克隆抗体G250修饰的肿瘤细胞靶向基因载体研究

用宫颈癌细胞Hela表面高表达G250抗原的单克隆抗体G250修饰非病毒基因载体, 获得肿瘤靶向基因载体. 通过注射G250杂交瘤细胞于小鼠腹腔, 制备富含G250mAb的腹水, 用正辛酸-硫酸铵沉淀法和Protein A Agarose分离纯化, 获得高纯度的G250mAb. 通过二硫键将PEI与G250mAb偶联, 得到修饰的基因载体G250mAb-PEI, 研究其转基因靶向性. 结果表明, G250mAb-PEI对Hela细胞的基因转染具有显著的靶向性, 对Hela细胞的转基因效率是肝癌细胞HepG2(G250阴性)的2倍; 而对正常血管平滑肌细胞(SMC)的基因转染效率比Hela低近20倍, G250mAb修饰与否对SMC没有靶向性; 对3T3细胞的毒性显著低于未修饰的PEI, 表明G250mAb-PEI是一种高效、低毒和具有靶向性的基因载体.     

基于双靶向黑色素纳米粒的肿瘤深穿透光声成像

通过1-(3-二甲基氨基丙基)-3-乙基碳二亚胺和N-羟基丁二酰亚胺反应将透明质酸(hyaluronic acid,HA)和4-羧丁基三苯基溴化膦((4-carboxybutyl) triphenylphosphonium bromide,TPP)分子连接到聚乙二醇-氨基(PEG-NH₂)修饰过的黑色素纳米颗粒(melanin nanoparticles,MNP)表面,设计合成了一种具有双靶向能力的黑色素纳米颗粒(MNP-TPP-HA),赋予了黑色素的双靶向能力。体外三维(3D)多细胞肿瘤球荧光成像和活体肿瘤光声成像实验表明MNP-TPP-HA具有优异的肿瘤靶向穿透能力。     

基于双靶向黑色素纳米粒的肿瘤深穿透光声成像

通过1‐(3‐二甲基氨基丙基)‐3‐乙基碳二亚胺和N‐羟基丁二酰亚胺反应将透明质酸(hyaluronic acid,HA)和4‐羧丁基三苯基溴化膦((4‐carboxybutyl) triphenylphosphonium bromide,TPP)分子连接到聚乙二醇-氨基(PEG‐NH₂)修饰过的黑色素纳米颗粒(melanin nanoparticles,MNP)表面,设计合成了一种具有双靶向能力的黑色素纳米颗粒(MNP‐TPP‐HA),赋予了黑色素的双靶向能力。体外三维(3D)多细胞肿瘤球荧光成像和活体肿瘤光声成像实验表明MNP‐TPP‐HA具有优异的肿瘤靶向穿透能力。     

肿瘤靶向PEI包覆磁性纳米凝胶的光化学制备及表征

以聚乙烯亚胺(Polyethyleneimine, PEI)为预聚体, H2O2为抽氢剂, 采用光化学方法制备了PEI包覆的磁性纳米凝胶(PEI-Fe3O4), 在PEI-Fe3O4表面共价偶联具有肿瘤靶向作用的叶酸分子(Folate, FA), 制备得到肿瘤靶向PEI包覆磁性纳米凝胶(FA-PEI- Fe3O4). 采用多种手段对PEI-Fe3O4及FA-PEI-Fe3O4进行了表征. 结果表明, FA-PEI-Fe3O4平均粒径为140 nm, 形状规则, 具有超顺磁性, 磁含量达到22.4%, 饱和磁化强度达65.6 A·m2·kg-1, 磁性纳米凝胶较高的磁响应性能和具有肿瘤靶向作用的叶酸分子的修饰, 为其作为潜在的肿瘤靶向载体奠定了基础.     

Darstellung,Kristallstrukturen, Schwingungsspektren und Normalkoordinatenanalyse von vier bindungsisomeren Trichlorotrirhodanoosmaten(IV)

Preparation, Crystal Structures, Vibrational Spectra, and Normal Coordinate Analysis of four Linkage Isomeric Trichlorotrirhodanoosmates(IV) By treatment of fac-[OsCl₃I₃]^2? with (SCN)₂ in dichloromethane the linkage isomers fac-[OsCl₃(NCS)₃]^2? ( 1 ), mer-[OsCl₃(NCS)₂^c(SCN)]^2? ( 2 ), mer-[OsCl₃(NCS)(SCN)₂^t]^2? ( 3 ), and mer-[OsCl₃(NCS)(SCN)₂^c]^2? ( 4 ) are formed which have been separated by ion exchange chromatography on diethylaminoethyl cellulose. X-Ray structure determinations have been performed on single crystals of fac-(Ph₄As)₂[OsCl₃(NCS)₃] (triclinic, space group P1 , a = 12.142(5), b = 13.233(5), c = 19.300(5) Å, α = 98.642(5)º, β = 100.509(5)º, γ = 112.514(5)º, Z = 2), mer-(Ph₄As)₂[OsCl₃(NCS)₂^c (SCN)] · acetone (triclinic, space group P1 , a = 11.707(5), b = 13.238(5), c = 19.048(5) Å, α = 75.960(5)º, β = 88.981(5)º, γ = 69.999(5)º, Z = 2), mer-(Ph₄As)₂[OsCl₃(NCS)(SCN)₂ ^t] (triclinic, space group P1, a = 10.6861(12), b = 11.6587(5), c = 12.5232(5) Å, α = 112.069(8)º, β = 95.052(8)º, γ = 92.559(7)º, Z = 1) and mer-(Ph₄As)₂[OsCl₃(NCS)(SCN)₂ ^c] · 2acetone (triclinic, space group P1 , a = 11.444(5), b = 14.661(5), c = 15.830(5) Å, α = 75.790(5)º, β = 80.273(5)º, γ = 75.205(5)º, Z = 2). The complex anions are completely ordered. The via N or S coordinated thiocyanate groups are located nearly direct above one of the cis-positioned Cl ligands with Os? N? C angles of 169.1º, 171.5º, 175.7º ( 1 ), 175.6º, 178.6º ( 2 ), 172º ( 3 ), and 173.1º ( 4 ) and Os? S? C angles of 106.2º ( 2 ), 106.1º, 106.6º ( 3 ), 105.1º, and 108.2º ( 4 ). Using the molecular parameters of the X-Ray determinations the low temperature (10 K) IR and Raman spectra of the (n-Bu₄N) salts of all four linkage isomers have been assigned by normal coordinate analyses based on a modified valence force field. The valence force constants are f_d(OsN) = 1.71 ( 1 ), 1.46 and 1.62 ( 2 ), 1.69 ( 3 ), and 1.61 ( 4 ), f_d(OsS) = 1.27 ( 2 ), 1.36 ( 3 ), 1.32, and 1.49 mdyn/Å ( 4 ). Taking into account increments of the trans influence a good agreement between observed and calculated frequencies is achieved.     

Darstellung,Kristallstrukturen, Schwingungsspektren und Normalkoordinatenanalyse von vier bindungsisomeren Tetrachlorodirhodanoosmaten(IV)

Preparation, Crystal Structures, Vibrational Spectra, and Normal Coordinate Analysis of Four Linkage Isomeric Tetrachlorodirhodanoosmates(IV) By treatment of cis- or trans-[OsCl₄I₂]^2? with (SCN)₂ in dichloromethane the linkage isomers cis-[OsCl₄(NCS)₂]^2? ( 1 ), trans-[OsCl₄(NCS)(SCN)]^2? ( 2 ), cis-[OsCl₄(NCS)(SCN)]^2? ( 3 ) and trans-[OsCl₄(SCN)₂]^2? ( 4 ) are formed which have been separated by ion exchange chromatography on diethylaminoethyl cellulose. The X-Ray structure determinations on single crystals of cis-(Ph₄As)₂[OsCl₄(NCS)₂] (triclinic, space group P1 , a = 10.019(5), b = 11.702(5), c = 21.922(5) Å, α = 83.602(5)°, β = 85.718(5)°, γ = 73.300(5)°, Z = 2), trans-(Ph₄As)₂[OsCl₄ · (NCS)(SCN)] (monoclinic, space group P2₁/c, a = 18.025(5), b = 11.445(5), c = 23.437(5) Å, β = 94.208(5)°, Z = 4), cis-(Ph₄As)₂[OsCl₄(NCS)(SCN)] (triclinic, space group P1 , a = 10.579(5), b = 11.682(5), c = 22.557(5) Å, α = 81.073(5)°, β = 85.807(5)°, γ = 87.677(5)°, Z = 2) and trans-(Ph₄As)₂ · [OsCl₄(SCN)₂] (triclinic, space group P1 , a = 10.615(5), b = 11.691(5), c = 11.907(5) Å, α = 111.314(5)°, β = 96.718(5)°, γ = 91.446(5)°, Z = 1) reveal the complete ordering of the complex anions. The via N or S coordinated thiocyanate groups are located nearly direct above one of the cis-positioned Cl ligands with Os? N? C angles of 171.2° and 174.3° ( 1 ), 162.3° ( 2 ), 172° ( 3 ) and Os? S? C angles of 108.3° ( 2 ), 105.7° ( 3 ) and 105.5° ( 4 ). Using the molecular parameters of the X-Ray determinations the low temperature (10 K) IR and Raman spectra of the (n-Bu₄N) salts of all four linkage isomers are assigned by normal coordinate analyses based on a modified valence force field. The valence force constants are f_d(OsN) = 1.59 ( 1 ), 1.67 ( 2 ), 1.60 ( 3 ) and f_d(OsS) = 1.27 ( 2 ), 1.31 ( 3 ) and 1.32 mdyn Å^?1 ( 4 ). Taking into account increments of the trans influence a good agreement between observed and calculated frequencies is achieved.     

Comparative Thermogravimetric Studies of Poly(ether-ketone/sulfone) Imides and Their Parent Polymers: I. Poly(ether-ketone/sulfone) ethylimide

Thermogravimetry (TG) was employed to study the thermal degradation kinetics of poly(etherketone/sulfone)ethylimide (PEK-IE and PES-IE). The corresponding decomposition activation energies and reaction orders were obtained and the comparison was made with their parent polymerspoly(ether-ketone/sulfone) with Cardo group (PEK-C and PES-C). The results show that the degradation activation energies of PEK-IE and PES-IE were lower than that of PEK-C and PES-C; and two stages of the degradation process were found for all the four polymers. For PEK-IE and PES-IE, the activation energies in the first decomposition stage are much lower than that in the second stage and the two stages can be taken as slow induction and fast degradation, whereas for PEK-C and PES-C the activation energies in the first decomposition stage are larger than that in the second stage, and the two stages can both be taken as two fast degradation stages. The decomposition mechanism of the two stages was also speculated.This revised version was published online in November 2005 with corrections to the Cover Date.     

Darstellung und Kristallstruktur von (n-Bu4N)3[Ir(NCS)(SCN)5]

Preparation and Crystal Structure of (n-Bu₄N)₃[Ir(NCS)(SCN)₅] The evaporated ethanolic extrakt of the reaction product of K₃[IrCl₆] and HNO₃, refluxed with an aqueous KSCN solution yields a mixture of the linkage isomers [Ir(NCS)_n(SCN)_6?-n]^3?, n = 0? 2, and small amounts of linkage isomeric chloropentarhodanoiridates(III), from which [Ir(NCS)(SCN)₅]^3? has been isolated by ion exchange chromatography on DEAE-cellulose. The X-Ray structure determination on a single crystal of (n-Bu₄N)₃[Ir(NCS)(SCN)₅] (monoclinic, space group P 2₁/a, a = 17.513(5), b = 32.607(5), c = 23.661(5) Å, β = 94.757(5)°, Z = 8) confirms the existance of a heteroleptic hexakis(thiocyanato(N)-thiocyanato(S))iridate(III) with an Ir? N distance of 2.03 Å and Ir? S bond lengths between 2.29 and 2.38 Å. The SCN groups with angles between 166 and 175° are nearly linear with Ir? S? C angles from 99.9 to 109.4°. The Ir? N? C angles of the two crystallographic independent anions are 166 and 174°.     

SYNTHESIS AND CHARACTERIZATION OF METAL COMPLEXES WITH AMPICILLIN

Abstract

The reaction, in water, of Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) ions with sodium ampicillinate at room temperature has allowed isolation of dimers with the following general formula [M(amp)Cl]₂ × nH₂O (n = 1.5?3.2). The complexes were characterized by elemental analyses, conductivity measurements, magnetic susceptibilities and spectroscopic methods (IR, Raman, EPR and UV-Visible). A dinuclear structure based on octahedrally coordinated metal ions is proposed.     

PMDA-BPDA-HAB聚苯并噁唑的合成及耐热性

PMDA-BPDA-HAB聚苯并噁唑的合成及耐热性;均苯四甲酸二酐;联苯四羧酸二酐;二羟基联苯胺;聚酰亚胺;聚苯并噁唑;耐热性     

Thermal Degradation of Poly(ε-caprolactone), Poly(L-lactic acid) and their Blends with Poly(3-hydroxy-butyrate) Studied by TGA/FT-IR Spectroscopy

Summary: The thermal degradation behavior of poly(ε-caprolactone) (PCL) and poly(L-lactic acid) (PLA) have been studied in different environment. It was found that these polymers undergo completely different degradation processes in nitrogen and oxygen atmosphere. In oxygen environment PCL and PLA mainly decompose to CO₂, CO, water and short-chain acids. In nitrogen atmosphere PCL releases 5-hexenioc acid, CO₂, CO and ε-caprolactone, whereas PLA decomposes to acetaldehyde, CO₂, CO and lactide. The polymer blends of poly(3-hydroxybutyrate) (PHB) with PCL and PLA decompose similar to the individual homopolymers with crotonic acid as the initial decomposition product of PHB.     

Energy relationship and the polarization of C_(60) cage in the endohedral complexes (X@C_(60))

In this paper, we carry out the calculation on the system (X@C60)(X=Li, Na, K, Kb, Cs; F, Cl, Br, I), where the position of X changes along 5 typical symmetry directions. For the calculation of quantum chemistry we use EHMO/ASED method, for the calculation of molecular mechanics we use Buckingham potential (exp-6-1) function, and for the calculation of thermo-chemical cycle we use individually isolating the processes such as the structure variation, charge transfer and charge distribution, and their interactions etc. The calculation results show that (1) In the region of radius r≈0.2 nm of the Ceo cage, the potential field is nearly spherical; (2) Except for Li and Na, the systems are the most stable with minimum energies at the center of C60 cage. For Li and Na, the systems are the most stable with minimum energies at r≈0.16 nm and r≈0.13 nm, respectively. In view of the interactive region of chemical bonds, the interactions between X and the C60 cage do not belong to the classical chemical bonds; (     

铜在3%NaCl溶液中腐蚀行为的光电化学研究

Cu以其优异的导电性、导热性和易加工性广泛用于工农业生产中．自然Cu的腐蚀和防腐成为人们很关注的问题．人们已经注意到，Cl-对Cu的腐蚀有影响，并进行过一些研究．但目前使用光电化学方法研究这一问题的文章尚不多见，特别是利用测量开路光电压及其瞬态波形这一现场的、无损的、灵敏的监测方法研究户对Cu电极腐蚀全过程的文章尚未见到．本文正是利用如上方法及XPS，AES方法，研究了Cl-对Cu电极腐蚀的全过程，取得了一些有意义的结果．1实验方法Cu电极用99．99％（质量分数）的Cu制成，面积约为39mm2；电极底部由Cu导线焊接引出，…     

On the morphological behavior of ABC miktoarm stars containing poly(cis 1,4-isoprene), poly(styrene), and poly(2-vinylpyridine)

Fundamental understanding of microphase separation in ABC miktoarm copolymers is vital to access a plethora of nonconventional morphologies. Miktoarm stars based on poly(cis 1,4-isoprene) (I), poly(styrene) (S), and poly(2-vinylpyridine) (V) are model systems, which allow systematic studies of the effects of composition, chemical microstructure, and temperature on the thermodynamics of microphase separation. Eleven ISV-x (I:S:V = 1:1:x, v:v:v) miktoarm copolymers were synthesized by anionic polymerization affording well-defined copolymers with a variable V arm. Equilibrium bulk morphologies of all samples, as evidenced by small-angle X-ray scattering, transmission electron microscopy (TEM), and self-consistent field theory, showed a systematic transition from lamellae (x ≈ 0–0.2) to [8.8.4] tiling (x ≈ 0.6–0.9) to cylinders in undulating lamellae (x ≈ 2–4) and, finally, to hexagonally packed core–shell cylinders (x ≈ 5–8). Chemical microstructure of the I arm [poly(cis 1,4-isoprene)] versus poly(3,4-isoprene) is shown to play important role in affecting morphological behavior. To reconcile differences between ISV-x star morphologies reported in the literature and those reported herein, even for the same composition, effects of the microstructure of I arm on the Flory–Huggins parameter between I and V arms were taken into account in a qualitative manner. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 1491–1504