PEI基因载体靶向遮蔽体系的制备和表征

将RGD短肽接枝到聚谷氨酸(PGA)上,制备了一种靶向性的基因载体遮蔽材料PGA-RGD.通过凝胶电泳实验及体外转染实验证明得出RGD的引入增加了载体材料与细胞表面受体的特异性作用,在载体表面正电荷得到遮蔽的同时,转染效率还得到了一定程度的增加.同时,对转染了48h的三元复合物进行MTT细胞毒性测试表明,PGA遮蔽的基因载体体系(PGA/PEI/DNA)和PGA-RGD遮蔽的基因载体体系(PGA-RGD/PEI/DNA)的细胞毒性均低于PEI/DNA复合物体系.本文开发的基因载体改性方法不仅可以对复合物颗粒表面的正电荷进行遮蔽,从而降低复合物体系对非目标组织的非特性异作用;同时引入的RGD靶向短肽还可以提高载体的靶向性,这一改性策略对推动阳离子聚合物基因载体在体内的应用具有重要意义.     

交联型聚乙烯亚胺智能基因载体的制备及PEG化影响

使用胱胺双丙烯酰胺(CBA)对低分子量聚乙烯亚胺(PEI)进行交联反应制备智能降解型聚阳离子基因载体.通过与聚乙二醇(PEG)反应得到不同程度PEG化的聚阳离子载体.利用核磁、黏度测试、粒度仪、zeta电位仪和凝胶电泳对聚阳离子载体及其与DNA的复合物进行了表征.研究表明随着PEG含量的增加,聚阳离子载体/DNA复合物颗粒粒径变小、表面正电荷降低,PEG具有明显的屏蔽作用,但过多的PEG也使载体与DNA复合能力下降.通过MTT细胞毒性测试和荧光素酶质粒转染实验得出,含二硫键的交联型阳离子聚合物在测试范围内显示了非常低的细胞毒性,最佳转染效率是PEI25k的4倍,PEG化后其细胞毒性得到进一步改善,转染效率却明显降低.     

有机锡化合物结构与电极性能的构效关系研究

系统研究了三类有机锡化合物的阴离子响应行为。结果表明,有机锡化合物的结构与电极响应行为之间呈现出非常密切的构效关系。三类有机锡化合物对水杨酸根离子均呈现出选择性的电位响应性能,其中四配位有机锡化合物对水杨酸根离子呈现近nernst响应,而五、六配位有机锡化合物对水杨酸根离子均呈现超nernst响应。更重要的是,载体中心原子上正电荷密度对电极响应性能有很大影响。随着与锡原子相连的有机基团性质的变化,载体对水杨酸根离子的电位响应性能和选择性均发生规律性的变化,通过hammett常数定性地描述了载体结构与电极性能的构效关系。同时,通过交流阻抗、膜红外光谱等技术对电极响应机制作了初步探讨,并对超nernst现象和六配位有机锡化合物的响应行为进行了解释。     

阳离子基因载体的pH敏感遮蔽体系的制备及表征

合成了一种pH敏感的遮蔽体系-谷氨酸苄酯/谷氨酸共聚物(PBLG-co-PGA), 用于对DNA/阳离子基因载体复合物颗粒表面正电荷的遮蔽, 以提高其在体内的稳定性. 研究表明, PBLG-co-PGA (PGA(x), x为PGA占共聚物中摩尔百分数)具有pH敏感性. 并以pH敏感点接近生理pH值的PGA(60)为遮蔽体系进行研究. PGA(60)能够对DNA/PEI(1:1)复合物颗粒表面正电荷进行有效遮蔽. 凝胶阻滞电泳显示, 用PGA(60)对DNA/PEI复合物进行不同比例遮蔽, 没有发生与DNA的链交换作用. MTT细胞毒性测试表明, PGA(60)和三元复合物DNA/PEI/PGA(60) 在测试范围内几乎没有细胞毒性. 荧光素酶转染实验表明, 部分遮蔽后转染效率有所提高; 用PGA(60)对DNA/PEI复合物完全遮蔽为负电后, 由于同细胞表面的电荷排斥作用, 三元复合物不易被细胞内吞, 导致不发生细胞转染. 因其合适的pH响应性, PGA(60)将可能成为一种能随pH值的变化, 实现对聚阳离子基因载体进行电荷遮蔽/智能释放的遮蔽材料.     

DDAB/Tween 80阳离子脂质体的构建与评价

阳离子脂质体是基因转染中最受关注的一种非病毒类载体。本文以双十二烷基二甲基溴化铵(DDAB)与聚山梨酯-80(Tween 80)复配构建阳离子脂质体,并评价其使用安全性和DNA压缩性能。结果显示,DDAB与Tween 80 5∶5复配形成的脂质体,粒径和Zeta电位适中,对溴酚蓝产生较强的包封作用;同时,可以有效地抑制DDAB的细胞毒性,在≤800μM时,红细胞溶血率5%,表现出优良的使用安全性;当该脂质体与DNA质量比为4时,对DNA显示出较强地结合压缩作用,且形成的复合物带有较高的正电荷(约+40 m V),这为基因转染提供了良好的理论基础。     

羟基取代苯并菲化合物分子的结构与电荷传输性质研究

在量子化学B3LYP/6-31G**水平上对苯并菲, 氟及羟基取代苯并菲化合物分子及其分子离子的结构进行理论研究, 得到稳定构型. 在此基础上, 计算二聚物的单点能随旋转角度和盘间距离的变化关系, 得到能量最低点. 根据电子转移的半经典模型计算了苯并菲及氟和羟基取代苯并菲化合物分子的电荷转移常数, 氟和羟基的引入使正电荷转移速率常数明显减小, 即不利于正电荷的传输, 对负电荷的传输速率常数影响不大.     

反向基因转染技术的最近研究进展

随着基因治疗研究的深入,基因转染技术得到了长足的发展。在反向基因转染概念被提出来的十余年间,反向基因转染技术也引起了广泛关注。反向基因转染技术是相对于常规转染而言的,即首先通过基质锚定DNA(或RNA),然后将细胞接种于该基质表面,细胞贴附的同时摄取锚定的DNA(或RNA)而实现基因转染,因而也被称为表面介导基因转染、基质介导基因转染、固相基因转染。与传统转染方法相比,其具备以下优势:载体/DNA(或RNA)复合物更加稳定,转染试剂可以更有效地接触细胞而达到更高的转染效率,低的细胞毒性和血清环境中不影响转染效率等。本文主要综述了反向转染技术的最新研究进展及其主要应用领域。     

模拟宿主防御肽的尼龙3抗菌聚合物结构设计、合成及活性研究

微生物感染一直是人类健康的严峻挑战,传统抗生素几乎不可避免地使微生物产生耐药性,因此亟待开发既对耐药细菌、真菌有活性,又不易使微生物产生耐药性的新型抗菌剂.宿主防御肽(host defense peptide,HDP)几乎存在于各种生命形式中并表现出广谱抗菌活性和不易使微生物产生耐药性的特点,近年来作为对抗微生物耐药性的新途径被广泛研究.为解决HDP自身稳定性差(容易被蛋白酶水解)的缺点,多个研究组相继开展HDP模拟物的研究,希望在改善抗菌剂稳定性的同时保持抗菌活性.尼龙3聚合物(β-多肽)是模拟HDP的一类代表性抗菌聚合物.尼龙3聚合物通常由一个亲水性/正电荷亚基和一个疏水性亚基通过不同比例组合来模拟HDP的2个关键性结构特点:正电荷和两亲性结构.通过优化端基基团和聚合物长度、变化亚基的化学结构、探索优化的亲水性/正电荷与疏水性亚基组合以及调节亚基在聚合物中的比例,发现了对多个耐药菌菌株具有高活性和高选择性的尼龙3聚合物.尼龙3对细菌营养细胞和稳定的孢子都显示了活性,同时尼龙3也对游离真菌细胞和真菌生物膜都表现出选择性抗菌活性.这些发现提示了尼龙3对抗微生物耐药性的潜力以及尼龙3作为新型抗菌剂的可能应用.     

Cos-7细胞胞内pH的31 P核磁共振测定

生物细胞内pH的测定对于细胞内代谢、游离离子及离子通道的研究有重要的意义,而且一些酶的活性也与细胞内pH密切相关。猴的肾细胞cos-7细胞常用于外源基因的转染表达,研究这一细胞株细胞内的pH,可为基因转染提供可靠的依据。本文采用^31P核磁共振对cos-7细胞胞内的pH进行了分析测定。     

一种层状化合物的水热合成及其特性

在１００－２５０℃温度范围内,用水热法合成了具有层状结构的化合物Ｌｉ２Ｏ２Ａｌ２Ｏ．ｎＨ２Ｏ．通过Ｘ－射线衍射分析了其结构特征,探索了合成条件对水热扫应产物的影响,用热分析研究了Ｌｉ２Ｏ．２Ａｌ２Ｏ３．ｎＨ２Ｏ的脱水过程,并确定化合物的含水率,用交流复平面阻抗谱测定了化合物在不同温度时的离子电导率,结果表明,用水热法成功地合成了具有较高离子电导率的单相Ｌｉ２Ｏ．２Ａｌ２Ｏ３．ｎＨ２Ｏ２化合物。     

Ion-chromatographic selectivity of polyelectrolyte sorbents based on some aliphatic and aromatic ionenes

An aliphatic ionene with hydroxyl group (2HP-8 ionene), mixed aliphatic-aromatic ionenes (3-X and 6-X ionenes), aromatic ionene (Ph-X ionene), and viologen (Dp-X ionene) - polymers with quaternary nitrogen atoms in the main chain served as modifiers in synthesising polyelectrolyte sorbents for ion chromatography. The selectivity of produced and several previously prepared anion exchangers was compared with those of aliphatic ionenes. It was found that aromatic ionenes having a rigid structure of polymer chains are similar to their aliphatic analogues with shorter chains with a high charge density. Polyelectrolyte sorbents based on aromatic ionenes show higher selectivity to aromatic acids (e.g., 1-naphthalenesulfonic acid) as compared with aliphatic ionenes due to specific pi-pi interactions.     

Transforming Ionene Polymers into Efficient Cathode Interlayers with Pendent Fullerenes

A new and highly efficient cathode interlayer material for organic photovoltaics (OPVs) was produced by integrating C₆₀ fullerene monomers into ionene polymers. The power of these novel “C₆₀‐ionenes” for interface modification enables the use of numerous high work‐function metals (e.g., silver, copper, and gold) as the cathode in efficient OPV devices. C₆₀‐ionene boosted power conversion efficiencies (PCEs) of solar cells, fabricated with silver cathodes, from 2.79 % to 10.51 % for devices with a fullerene acceptor in the active layer, and from 3.89 % to 11.04 % for devices with a non‐fullerene acceptor in the active layer, demonstrating the versatility of this interfacial layer. The introduction of fullerene moieties dramatically improved the conductivity of ionene polymers, affording devices with high efficiency by reducing charge accumulation at the cathode/active layer interface. The power of C₆₀‐ionene to improve electron injection and extraction between metal electrodes and organic semiconductors highlights its promise to overcome energy barriers at the hard‐soft materials interface to the benefit of organic electronics.     

Naphthalene-Diimide-Based Ionenes as Universal Interlayers for Efficient Organic Solar Cells

Self-doping ionene polymers were efficiently synthesized by reacting functional naphthalene diimide (NDI) with 1,3-dibromopropane ( NDI-NI ) or trans-1,4-dibromo-2-butene ( NDI-CI ) via quaternization polymerization. These NDI-based ionene polymers are universal interlayers with random molecular orientation, boosting the efficiencies of fullerene-based, non-fullerene-based, and ternary organic solar cells (OSCs) over a wide range of interlayer thicknesses, with a maximum efficiency of 16.9 %. NDI-NI showed a higher interfacial dipole (Δ), conductivity, and electron mobility than NDI-CI , affording solar cells with higher efficiencies. These polymers proved to efficiently lower the work function (WF) of air-stable metals and optimize the contact between metal electrode and organic semiconductor, highlighting their power to overcome energy barriers of electron injection and extraction processes for efficient organic electronics.     

Naphthalene‐Diimide‐Based Ionenes as Universal Interlayers for Efficient Organic Solar Cells

Self‐doping ionene polymers were efficiently synthesized by reacting functional naphthalene diimide (NDI) with 1,3‐dibromopropane ( NDI‐NI ) or trans‐1,4‐dibromo‐2‐butene ( NDI‐CI ) via quaternization polymerization. These NDI‐based ionene polymers are universal interlayers with random molecular orientation, boosting the efficiencies of fullerene‐based, non‐fullerene‐based, and ternary organic solar cells (OSCs) over a wide range of interlayer thicknesses, with a maximum efficiency of 16.9 %. NDI‐NI showed a higher interfacial dipole (Δ), conductivity, and electron mobility than NDI‐CI , affording solar cells with higher efficiencies. These polymers proved to efficiently lower the work function (WF) of air‐stable metals and optimize the contact between metal electrode and organic semiconductor, highlighting their power to overcome energy barriers of electron injection and extraction processes for efficient organic electronics.     

基于富勒烯和噻吩聚合物的本体异质结太阳电池

随着全球能源需求量的逐年增加,对可再生能源的有效利用成为亟待解决的问题。现在使用的能源多来自矿物燃料的开采,其中包括石油、天然气和煤等,而这些资源是非常有限的。因此,发展新能源和新能源材料是我国进入21世纪必须解决的重大课题,其中太阳能被认为是清洁可再生新能源的代表之一。基于噻吩跟富勒烯的异质结太阳能电池是目前太阳能电池的重要发展方向之一。该种太阳能电池因其制备简单、成本低廉、重量轻和可制成柔性器件等优点近年来受到多方的广泛重视。经过努力,该种太阳能电池的光电转化性能已经得到了一定提高,最高光电转化效率已达到7%左右,但是跟无机半导体硅和染料敏化太阳能电池相比还有一定差距。因此,这方面的研究任重而道远,研究空间也非常大。本文从材料合成的角度,简要综述了近年来国内外在基于富勒烯和噻吩的异质结太阳能电池方面所取得的最新研究进展,并对下一步需要研究的热点问题作了展望。     

不同桥联二噻吩低带隙给受体共聚物的电子结构和光物理性质的理论研究

本文主要是通过分析吸收光谱性质来区分用于体异质结聚合物太阳能电池的两种不同桥联低带隙给受体共聚物PCPDTBT和PSBTBTS的激发态特征,进而通过分析电荷转移态（CT）特征来区分二者实现电荷分离的难易程度. 利用密度泛函理论(DFT/TD-DFT)B3LYP和CAM-B3LYP方法计算PSBTBT和PCPDTBT(n=1~4)的电子结构和光谱性质. 结果表明,从吸收光谱来看,PSBTBT与PCPDTBT的光谱相似,与太阳光谱的匹配能力相当. 而激子解离能表明二者的电荷转移态（CT）电荷分离的难易程度也相当. 然而用Si原子取代C原子后,C-Si键长明显长于C-C键长,降低了噻吩环和烷基链间的空间位阻,从而可能有利于其结晶度的提高,更加有利于载流子的传输,因此从理论上说明PSBTBT也可能具备高效太阳能电池给体材料的潜质.     

Photovoltaic Properties of Titanium Dioxide Nanowires with Different Crystal Structures

Titanium dioxide(TiO₂) nanowires with different crystal structures were successfully synthesized, and their charge transfer properties were further investigated by surface photovoltage(SPV), transient photovoltage(TPV) and surface photocurrent(SPC) techniques. The results reveal that both the surface states and the charge transfer rate of different TiO₂ nanowires are highly dependent on their crystal structures.     

Hydrogen bonds in polycation improve the gene delivery efficiency in the serum-containing environment

Cationic polymers with high charge density could effectively condense the DNA and achieve gene transfection; however, it often brings non-negligible cytotoxicity. Notably, the high charge density gene vector fails in the serum environment, limiting further application in vivo. In this paper, an efficient and reliable non-viral gene vector of poly (amidoamine) (PAA) was designed by introducing diacryolyl-2,6-diaminopyridine (DADAP) onto the PAA backbone through Michael-addition polymerization, which provides high transfection efficiency in a serum-containing environment. Diacryolyl-2,6-diaminopyridine and cationic parts provided multiple interactions between gene vectors and DNA, including hydrogen bond and electrostatic interactions. The introduction of hydrogen bonding can effectively reduce the charge density of polyplexes without reducing the DNA condensing ability, incorporating the diaminopyridine group and cationic part in PAA chains successfully consolidated cellular uptake, endosome destabilization, and transfection efficiency for the PAA/DNA complexes with low cytotoxicity. The constructed vector with multiple interactions presented 6 times higher transfection efficiency in serum-free and 9 times in serum-containing environment than that of branched polyethyleneimine (PEI 25K) in 293T cells in vitro. Therefore, introducing the hydrogen band to form low charge density polyplexes with high transfection efficiency and low cytotoxicity has a great potential in gene delivery.     

Isothermal titration calorimetry and molecular dynamics study of ion-selectivity in mixtures of hydrophobic polyelectrolytes with sodium halides in water

Aliphatic x,y-ionenes are polyelectrolytes in which x and y denote the numbers of methylene groups separating quaternary ammonium ions. They represent useful model substances for studying hydrophobic and charge effects in aqueous solutions. We used isothermal titration calorimetry to measure the enthalpies of mixing, ΔH(mix), of 3,3- and 6,6-ionene fluorides and bromides with low molecular weight salts (NaF, NaCl, NaBr, and NaI) at 298 K in water. The signs and magnitudes of the measured enthalpies depend on the hydrophobicity of the ionene and on the nature of the added salt. For example, addition of sodium fluoride to solutions of 3,3- and 6,6-ionene fluorides produced endothermic effects, while addition of sodium bromide to 3,3-ionene bromide resulted in a strong exothermic effect. Interestingly, mixing of 6,6-ionene bromide and NaBr solutions in water gave a small exothermic heat effect. Polyelectrolyte theories, based on continuum-solvent models, predict enthalpies of mixing to be positive (endothermic) for all the solutions examined in this work. The ion-specific effect is more strongly expressed in ionene solutions with higher charge density (3,3-ionene). The most important result of this work is the finding that the enthalpy of mixing of 3,3- (and of 6,6-ionene) fluorides with sodium halides can be expressed as a linear function of the enthalpy of hydration of the halide counterions. The experimental results were complemented with an explicit water molecular dynamics simulation of solutions of oligoions modelling 3,3- and 6,6-ionenes. The computer simulation results for various nitrogen-counterion pair distribution functions were in most cases consistent with the enthalpy measurements.     

Ultrafast intramolecular exciton splitting dynamics in isolated low-band-gap polymers and their implications in photovoltaic materials design

Record-setting organic photovoltaic cells with PTB polymers have recently achieved ~8% power conversion efficiencies (PCE). A subset of these polymers, the PTBF series, has a common conjugated backbone with alternating thieno[3,4-b]thiophene and benzodithiophene moieties but differs by the number and position of pendant fluorine atoms attached to the backbone. These electron-withdrawing pendant fluorine atoms fine tune the energetics of the polymers and result in device PCE variations of 2-8%. Using near-IR, ultrafast optical transient absorption (TA) spectroscopy combined with steady-state electrochemical methods we were able to obtain TA signatures not only for the exciton and charge-separated states but also for an intramolecular ("pseudo") charge-transfer state in isolated PTBF polymers in solution, in the absence of the acceptor phenyl-C(61)-butyric acid methyl ester (PCBM) molecules. This led to the discovery of branched pathways for intramolecular, ultrafast exciton splitting to populate (a) the charge-separated states or (b) the intramolecular charge-transfer states on the subpicosecond time scale. Depending on the number and position of the fluorine pendant atoms, the charge-separation/transfer kinetics and their branching ratios vary according to the trend for the electron density distribution in favor of the local charge-separation direction. More importantly, a linear correlation is found between the branching ratio of intramolecular charge transfer and the charge separation of hole-electron pairs in isolated polymers versus the device fill factor and PCE. The origin of this correlation and its implications in materials design and device performance are discussed.