基于透明质酸构筑的药物递送载体及其应用

传统纳米药物控释载体主要通过细胞胞吞作用实现药物递送,其主要过程为被动靶向机制,因此会影响纳米载体在肿瘤组织的富集和治疗效果.近年来生物大分子透明质酸因其优异的水溶性、生物相容性、可降解性和肿瘤靶向性备受科研工作者青睐,已被广泛用于药物控释载体的构筑中,并成为靶向肿瘤治疗纳米载体领域的研究热点.本文根据透明质酸基纳米载...     

用于膀胱癌灌注治疗的纳米药物研究进展

膀胱癌是泌尿系统多发肿瘤之一,在新发膀胱癌中约75%为非肌层浸润性膀胱癌,其标准治疗手段为行经尿道膀胱肿瘤切除术,并在术后进行膀胱灌注治疗。然而,膀胱组织因其特殊的生理特性,导致排泄过程中,药物在膀胱内滞留时间短,使得膀胱灌注仅在短期内有效。近几年来,膀胱内腔灌注药物载体得到了发展,即通过导管将负载有药物的多种纳米载体材料输送到膀胱内腔中。纳米载体由于其合适的粒径、表面特性及与膀胱壁黏膜层的直接相互作用,可以有效延长药物在膀胱内腔的滞留时间,增加其在膀胱内壁组织的粘附性和穿透力,从临床应用角度讲,是安全的膀胱内药物递送方式,因而引起材料学界和临床医学界的广泛关注。本文针对这一类膀胱内腔给药载体材料进行系统概述,以治疗方法为分类依据,总结了目前多种形式的纳米粒子的治疗效果,还对这些纳米粒子存在的共性问题进行概括,并提出了可能的解决方法,以期为材料的设计研究以及临床应用提供指导与借鉴。     

纳米药物在肿瘤治疗与临床应用的发展与挑战

纳米药物是指具有纳米尺度的药物颗粒或载体与药物形成的纳米载药颗粒.与传统药物相比,纳米药物载体尺寸小且比表面积大,药物负载量增加、体内循环时间增长,从而提高疗效,并降低毒副作用.本文总结了脂质体、蛋白质和碳量子点等作为载体的纳米药物的结构、功能、生物学性质,概述了纳米药物在肿瘤治疗领域中的临床应用进展及其作为核酸疫苗在席卷全球的新型冠状病毒肺炎疫情中的重大贡献,分析了其在临床应用中的问题、挑战与发展前景,旨在为纳米药物在医药领域中的研发提供参考,促进纳米药物的临床应用.     

温度敏感性药物载体及其在肿瘤热化疗中的应用

温度敏感性材料由于其理化性质对温度变化高度敏感,同时相变温度又易于调控,因而成为条件响应型药物控释载体中的研究热点。多种类型的温敏性药物载体,包括脂质体、聚合物囊泡、聚合物胶束,经过多年的研究和优化,其稳定性得到进一步的提高,而相变温度也实现了在较宽范围内的随意调整,可同时适用于病理性的高热和局部人工热疗等多种方式的温敏靶向性释药。并且,由于局部热疗可以有效控制温敏载体的药物释放,同时,热疗还能有效增强化疗药物的细胞毒性,因此温敏药物载体在肿瘤化疗和热化疗领域具有独特的应用潜力。本综述简要回顾了温敏性载体在药物载体领域的研究现状。在此基础上,从对肿瘤热化疗原理、发展现状、疗效影响因素的角度,进一步综述了温敏性药物载体在肿瘤热化疗领域的研究进展,特别关注了复合型温敏载体,因为这类载体结合了具有光热/磁热效应的纳米颗粒而兼具自升温能力,因而在靶向性热化疗中独具优势。最后,本文结合热化疗的影响因素,对温敏性载体在肿瘤热化疗领域的发展方向进行了展望。     

基于上转换荧光纳米材料的智能响应药物系统在肿瘤治疗中的应用

上转换荧光纳米粒子具有优异的理化性质,如稳定的发光性能、可调的发射光谱及相对较低的生物毒性,使其在肿瘤治疗领域展现出较好的应用前景.但是很多上转换纳米粒子介导的肿瘤治疗在可控性及选择性方面仍存在不足,无法有效减小对正常组织的损伤,从而阻碍了其在肿瘤治疗中的进一步发展.合理的结构设计和功能化组装,可以构建上转换纳米粒子智能响应系统.这不仅弥补了传统肿瘤治疗的缺陷,也为开发具备可控性和选择性的肿瘤治疗方案提供了新的思路.本文主要对上转换纳米粒子智能响应药物系统的刺激因素及构建方式进行简要的分析,同时总结了它们在肿瘤治疗中的应用和研究现状,并在此基础上对它们在未来肿瘤治疗中的挑战进行了分析和展望.     

细胞膜修饰的纳米载体与肿瘤免疫治疗

纳米载体由于其纳米尺度带来的独特生物功能性,可通过特定设计在生物体内靶向递送各类抗肿瘤药物,具有广泛而重要的应用前景。自肿瘤免疫疗法问世之后,各类纳米载体与肿瘤免疫治疗相结合,逐渐成为提升肿瘤免疫治疗效果的重要手段之一。其中,细胞膜修饰的纳米载体作为一类新型仿生药物载体平台,可使纳米载体获得天然细胞膜的伪装修饰,将细胞膜的特定功能与生物特性转移至纳米载体,使其具有更强的抗免疫清除、血液长循环和肿瘤靶向等特性,同时降低纳米递送系统的免疫原性和细胞毒性,在生物医学应用领域尤其是肿瘤免疫治疗中可发挥更大的作用。本文通过结合免疫治疗的机理,对近年来各种细胞膜修饰纳米载体系统的制备方法、作用机制以及在肿瘤免疫治疗中的应用研究进行综述,并在此基础上对未来的相关探索做出了展望。     

基于环糊精聚合物主客体作用制备智能纳米药物载体研究进展

智能纳米药物载体凭借其独特的刺激-响应机制实现按需药物释放,已成为当前研究的热点。环糊精由于其天然的大环结构、无毒、价格低廉、容易组装等特点已被广泛应用于药物载体。基于环糊精聚合物与其它客体分子的相互作用为构建智能纳米药物载体提供了灵活而强大的平台。这种智能纳米药物载体可以在外界刺激下做出相应的理化性质的改变,从而达到控制药物释放的目的。本文综述了基于环糊精主客体作用制备智能药物载体的最新研究进展及其应用。     

功能化金属-有机框架材料在肿瘤治疗中的研究进展

恶性肿瘤由于其易转移、复发等特点，已经严重危害到人类的生命健康.近年来，研究人员设计了大量纳米药物载体，将抗肿瘤药物安全有效地运载到肿瘤，有效地提高了药效并降低了毒副作用.金属有机框架材料（metal-organic frameworks，MOFs）是一类有序、多孔的晶态材料，具有比表面积大、结构可设计性强、易生物降解等独特优势，已经被广泛应用于气体吸附与分离、催化、药物传递、生物大分子固载以及肿瘤治疗等方面.目前，基于MOFs的生物医用研究主要集中在MOF材料的可控合成，表面修饰，基于MOF独特理化性质发展的多模式成像技术以及肿瘤靶向的药物运载技术等几个方面.主要介绍了基于MOFs构建的生物功能化材料在肿瘤治疗中的应用，并对其在生物医学领域的应用进行了展望.     

透明质酸修饰的介孔二氧化硅包覆金纳米棒的制备及在肿瘤化疗-热疗联合治疗中的应用

通过在包覆了金纳米棒的介孔硅表面修饰生物相容性的透明质酸, 得到了具有肿瘤靶向性的多功能药物载体. 实验结果表明, 透明质酸可以通过酰胺键修饰在介孔硅表面, 所得药物载体可在透明质酸酶作用下实现选择性释放. 该体系在近红外区域具有较高的吸收, 可以在近红外光照射下实现光热转换. 细胞实验结果表明, 该多功能药物载体可以有效靶向CD44过量表达的乳腺癌细胞, 通过CD44介导的内吞富集在肿瘤内部, 结合化学药物治疗和光热治疗, 显示出更高的肿瘤细胞凋亡效率.     

聚合物胶束作为药物载体的研究进展

聚合物胶束是具有疏水核心和亲水壳的自组装纳米颗粒.作为一种新型的药物载体,聚合物胶束具有载药范围广、结构稳定、体内滞留时间长、毒副作用小等特点.可以通过肿瘤组织的高通透性和滞留效应被动地富集在癌组织中,也可以通过修饰聚合物胶束的表面基团来实现药物靶向给药.本文总结并分析了聚合物胶束作为药物载体的研究进展,包括聚合物胶束的功能特点、制备、应用和药物的包载.     

Dichroism of absorption and polarization of phosphorescence of molecules of the closed form of nitrobenzospirothiopyran

The spectral-polarization characteristics of absorption and phosphorescence of molecules of the initial form of nitro-substituted indolinospirobenzothiopyran were studied in oriented polyethylene films and in solutions with different polarity. An oscillator model of the electron transitions responsible for the formation of absorption and luminescence spectra was suggested. It was established that the principal differences in the spectral and photophysical properties of the compound studied and its oxygen-containing analog are associated with the fact that the electronegativity of the S atom is lower than that of the O atom. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1143–1146, June, 1997.     

非那雄胺合成工艺改进

非那雄胺能抑制5α-还原酶的活性,明显降低二氢睾酮水平,是一种治疗良性前列腺增生的有效药品。该合成工艺以甾烯酮酸为原料,将其与氯化亚砜反应,无须分离即与叔丁胺反应得17β-酰胺化合物,再氧化开环,环合,氢化,脱氢合成了非那雄胺。经元素分析、IR、1HNMR、13CNMR、MS分析表征了其结构。该法无须使用昂贵的2,2-二吡啶二硫化物和剧毒药品苯亚硒酸酐,且以乙酸铵代替氨气,降低了对设备的要求和腐蚀,更适用于工业生产。     

Determination of heats of detonation and influence of components of composite explosives on heats of detonation of high explosives

The heats of detonation of 20 simple high explosives and explosive mixtures were determined by means of an adiabatic detonation calorimeter designed by the authors. The results indicated that the performance of the instrument was reliable and the experimental data were very accurate. For explosive mixtures, there was a linear accumulative relationship between the heats of detonation of the explosive mixture and its components. Accordingly, the heats of detonation of explosive mixtures could be calculated directly from the heats of detonation of simple explosives and the characteristic heats of other components. The experiments showed that the gold or brass shell of the cylindrical charge could be substituted by a thick-walled porcelain shell, which had the advantage of cheapness.

     

Synthesis of phenolic components of Grains of Paradise

Two vanilloids, (5E)-8-(4-hydroxy-3-methoxyphenyl)oct-5-en-4-one (1) and 4-[3-hydroxydecyl]-2-methoxyphenol (2), isolated from the dried seeds of Grains of Paradise (Aframomum melegueta), were synthesized; the latter compound was made as the S-enantiomer and the material derived from the seeds was found to be a 1:1.7 mixture of the R and S isomers. The synthetic route used should allow the preparation of analogs having extended alkyl chains and consequently different lipophilicity, and 3, a homolog of 2, was also prepared.     

Summary of development of the theory of stability of colloids and thin films

In this review, the research of the author in the field of colloidal systems is summarized. The factors influencing colloidal stability are systematized and analyzed. Examples are presented to illustrate the practical utilization of the theory of stability of colloids and thin films.This review was prepared on the basis of the works of the author, which were awarded the State Premium for 1991 in the field of science and technology, chemistry section.Institute of Physical Chemistry, Russian Academy of Sciences, 117915 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 8, pp. 1708–1717, August, 1992.     

Study of hydration of two cements of different strengths

Main hydration products of two cement pastes, i.e. CSH-gel, portlandite (P) (and specific surface S) were studied by static heating, and by SEM, TEM and XRD, as a function of cement strength (C-33 and C-43) hydration time (th) and subsequent hydration in water vapour.Total change in mass on hydration and air drying, M_o, increased with strength of cement paste and with hydration time. Content of water escaping at 110 to 220°C, defined as water bound with low energy, mainly interlayer and hydrate water, was independent on cement strength but its content increased with (th). Content of chemically bound (zeolitic) water in CSH-gel, escaping at 220-400°C, was slightly dependent on strength and increased with (th). It was possibly derived from the dehydroxylation of CSH-gel and AFm phase. Portlandite water, escaping at 400-500°C, was independent on cement strength and was higher on longer hydration. Large P crystals were formed in the weaker cement paste C-33. Smaller crystals were formed in C-43 but they increased with (th). Carbonate formated on contact with air (calcite, vaterite and aragonite), decomposed in cement at 600-700^oC. It was high in pastes C-33(1 month) and C-43(1 month), i.e. 5.7 and 3.3%, respectively; it was less than 1% after 6 hydration months (low sensitivity to carbonation) in agreement with the XRD study showing carbonates in the air dry paste (1month), and its absence on prolonged hydration (6 months) and on acetone treatment. Water vapour treatment of (6 months) pastes or wetting-drying increased this sensitivity.Nanosized P-crystals, detected by TEM, could contribute to the cement strength; carbonate was observed on the rims of gel clusters.This revised version was published online in November 2005 with corrections to the Cover Date.     

氯氧化镁生成热的研究

用氧化镁氯化镁水溶液制备了8水合氯氧化镁[nMg(OH)2·MgCl2·8H2O], 并测定了其在盐酸中的溶解热, 实验结果表明, 氯氧化镁溶解热与n值呈线性关系, 根据溶解热求出5Mg(OH)2·MgCl2·8H2O和3Mg(OH)2·MgCl2·8H2O的生成热分别为-7727.1和5888.1kJ·mol^1^-。     

Thermodynamics of the formation of oxosulfides of rare-earth elements

The enthalpies of solution of several oxosulfides of rare-earth elements and the high-temperature enthalpies of oxosulfides and oxosulfates of lanthanum and yttrium were measured using solution calorimetry and high-temperature microcalorimetry techniques. Standard enthalpies of formation and some thermodynamic properties of oxosulfides and oxosulfates were calculated. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2 pp. 294–297, February, 1997.     

恶臭嗅辨实验室建设探讨

针对恶臭测试的环境影响问题,提出了解决的实例方案,并对方案的要点及优缺点进行讨论,此方案在实际操作中具有较好的效果。