细胞膜伪装的纳米载体用于光热治疗的研究进展

纳米载体一直是肿瘤精准治疗的重要研究领域。其中以细胞膜伪装的纳米药物载体作为一种新颖的药物载体平台,在近年来已成为药物传递领域的研究热点。本文综述了不同种类细胞膜伪装的纳米载体应用于光热治疗的最新进展。将细胞膜与纳米材料结合起来,可进一步推进纳米载体的研究,这将对相关领域的发展产生重要影响。     

Synthesis and Characterization of Reversible Chemosensory Polymers: Modulation of Sensitivity through the Attachment of Novel Imidazole Pendants

Three novel electron donor–acceptor conjugated polymers ( P1 – P3 ) bearing various imidazole pendants have been synthesized. Their excellent photophysical and electrochemical properties make them suitable transduction materials for chemosensing applications. Indeed, polymers P1 – P3 have been found to show remarkable sensing capabilities towards H⁺ and Fe²⁺ in semi‐aqueous solutions. Upon titration with H⁺, polymers P1 and P2 showed hypsochromic shifts of their absorptions and photoluminescence (PL) maxima with enhanced fluorescence intensities. However, P3 showed diminished absorption and fluorescence intensities under similar conditions due to static quenching. The anomalous behavior of P3 compared with P1 and P2 has been clarified in terms of electronic distributions through computational analysis. Furthermore, P3 (K_SV=1.03×10⁷) showed a superior sensing ability towards Fe²⁺ compared with P1 (K_SV=2.01×10⁶) and P2 (K_SV=4.12×10⁶) due to its improved molecular wire effect. Correspondingly, the fluorescence lifetime of P3 was greatly decreased (almost 11‐fold) compared to those of polymers P1 (4.6‐fold) and P2 (6.2‐fold) in the presence of Fe²⁺. By means of a fluorescence on‐off‐on approach, chemosensing reversibilities in protonation–deprotonation and metallation–demetallation have been achieved by employing triethylamine (TEA) and the disodium salt of ethylenediaminetetraacetic acid (Na₂‐EDTA)/phenanthroline, respectively, as suitable counter ligands. ¹H NMR titrations have revealed the unique behavior of P3 compared with P1 and P2 . To the best of our knowledge, there have been no previous reports of Fe²⁺ sensors based on single imidazole receptors conjugated to a main‐chain polymer showing such a diverse sensitivity pattern depending on their attached substituents.     

Gold Nanoparticles Grown on Ionic Liquid‐Functionalized Single‐Walled Carbon Nanotubes: New Materials for Photothermal Therapy

Gold nanoparticles were grown on single‐walled carbon nanotubes (SWNTs) coated with a thiol‐functionalized ionic liquid resulting in the formation of core‐shell structures referred to as SWNT‐IL‐Au nanohybrid materials. The nanohybrid materials were characterized by high‐resolution transmission electron microscopy (HR‐TEM), Raman‐, and UV/Vis absorption spectroscopy. The nanohybrid materials were found to enter lysosomes in HeLa cells and show negligible cytotoxicity. Interestingly, they have an enhanced NIR absorption that is effectively transferred into heat to cause localized hyperthermia, resulting in rapid cell death; overall, the material appears to have excellent properties for photothermal therapeutic applications.     

Effects of adenovirus-mediated bFGF, IL-1Ra and IGF-1 gene transfer on human osteoarthritic chondrocytes and osteoarthritis in rabbits

The study investigated the effects of adenovirus-mediated gene transfection of basic fibroblast growth factor (bFGF), bFGF combined with interleukin-1 receptor antagonist protein (IL-Ra) and/or insulin-like growth factor-1 (IGF-1) both in human osteoarthritis (OA) chondrocytes and rabbits OA model. Human OA chondrocytes were delivered by adenovirus-mediated bFGF, IL-Ra and IGF-1 vectors, respectively. Chondrocyte proliferation, glycosaminoglycan (GAG) content, expression of type II collagen, ADAMTS-5, MMP-13, MMP-3 and TIMP-1 were determined. Rabbit OA model was induced by anterior cruciate ligament transaction (ACLT) in knees. Adenoviral vectors encoding human bFGF, IL-Ra and IGF-1 were injected intraarticularly into the knee joints after ACLT. The effects of adenovirus- mediated gene transfection on rabbit OA were evaluated. In vitro, the transfected genes were expressed in cell supernatant of human OA chondrocytes. AdbFGF group significantly promoted chondrocyte proliferation, and increased GAG and type II collagen synthesis than in the OA group. As two or three genes were transfected in different combinations, there was significant enhancement on the GAG content, type II collagen synthesis, and TIMP-1 levels, while ADAMTS-5, MMP-13, and MMP-3 levels were reduced. In vivo, the transfected genes were expressed in synovial fluid of rabbits. Intraarticular delivery of bFGF enhanced the expression of type II collagen in cartilage and decreased cartilage Mankin score compared with the OA control group (P = 0.047; P < 0.01, respectively). Multiple-gene transfection in different combinations showed better results than bFGF transfection alone. This study suggests that bFGF gene transfection is effective in treating experimental OA. Multiple gene transfection has better biologic effects on OA.     

具有聚集诱导发光性质的近红外荧光染料

聚集诱导发光(AIE)现象的发现为解决传统有机荧光分子在高浓度和聚集形态下存在的荧光猝灭问题提供了最佳方案,并实现了在光电器件、化学传感、生物成像和靶向治疗等众多领域的广泛应用。随着对AIE发光机理研究的不断深入,AIE分子体系得到了极大的扩展。其中,一类具有给体-受体结构的AIE分子能够显著降低分子能隙,使发光分子波长从可见光区(400~700 nm)延伸到近红外(NIR)区(700~1700 nm)。由于NIR发光分子在生物医学领域中的独特优势,其已成为目前AIE研究的热点。随着对NIR分子设计及应用的不断探索,附加不同功能且发光波长更长的AIE分子也被开发出来了,并实现了对生物体特定组织的NIR荧光成像、光声成像、光动力治疗和光热治疗等。本文总结了近年来具有AIE性能的NIR荧光分子的结构及其在生物医学领域的相关应用。     

Selection of aptamers for signal transduction proteins by capillary electrophoresis

High‐affinity aptamers for important signal transduction proteins, i.e. Cdc42‐GTP, p21‐activated kinase1 (PAK1) and MRCK (myotonic dystrophy kinase‐related Cdc42‐binding kinase) α were successfully selected in the low micro‐ to nanomolar range using non‐systematic evolution of ligands by exponential enrichment (SELEX) with at least three orders of magnitude enhancement from their respective bulk affinity of naïve DNA library. In the non‐SELEX procedure, CE was used as a highly efficient affinity method to select aptamers for the desired molecular target through a process that involved repetitive steps of partitioning, known as non‐equilibrium CE of equilibrium mixtures with no PCR amplification between successive steps. Various non‐SELEX conditions including the type, concentration and pH of the run buffer were optimized. Other considerations such as salt composition of selection buffer, protein concentration and sample injection size were also studied for high stringency during selection. After identifying the best enriched aptamer pool, randomly selected clones from the aptamer pool were sequenced to obtain the individual DNA sequences. The dissociation constants (K_d) of these sequences were in the low micromolar to nanomolar range, indicating high affinity to the respective proteins. The best binders were also subjected to sequence alignment to generate a phylogenetic tree. No significant consensus region based on approximately 50 sequences for each protein was observed, suggesting the high efficiency of non‐SELEX for the selection of numerous unique sequences with high selectivity.     

微型光热驱动机构的光热膨胀理论模型与实验研究

提出和发展了一种基于微尺度光热膨胀效应的微型光热驱动机构.建立了膨胀臂的微尺度光热传导与膨胀的物理模型,利用有限元分析和数学物理方法,推导出膨胀臂的一维温度分布表达式及光热膨胀量和偏转量的计算公式.利用准分子激光微加工系统设计制作了一个长度为1200?μm 的微型光热驱动样机,根据激光和样机的相关参数,计算得到光热膨胀量与激光功率之间的理论关系曲线.实验结果表明,微型光热驱动机构的光热偏转量（对应于膨胀量）与照射到膨胀臂上的激光功率近似成线性关系,实验曲线与理论模型及计算结果符合良好.在理论和实验研究基础上,作为光热微驱动的应用实例,设计并加工制作了一个双向微开关型光热驱动机构,并通过实验实现了双向微开关功能. 关键词： 光热膨胀臂 微驱动机构 光热传导模型 激光     

光热显微术:基于光吸收的单分子成像技术

光热显微术是近年来获得广泛关注和长足发展的一种新型光学显微成像技术,能够实现单个纳米粒子甚至单分子的免标记光学成像。其成像原理是利用先进的光学方法探测单分子或单纳米粒子吸收特定波长激发光后所产生的局域温度和介质折射率的微小变化,从而定量研究观测对象的光热特性。由于无辐射弛豫是激发态分子回到基态的优势过程,分子的光热特性相比于荧光特性更具有普遍意义。凭借无需标记、高灵敏度和信号稳定等优点,近十年来,关于单分子和单纳米粒子的光热显微成像研究不断取得突破,并在纳米科学和生命科学等领域获得越来越多的发展和应用,展现出了蓬勃的生命力和良好的发展前景。本文重点综述了光热显微技术的成像原理、发展历程、技术特色以及系统优化方法,列举了光热成像在活细胞研究和生物学领域的应用,最后总结了光热成像的优缺点并分析其主要面临的挑战以及未来的发展趋势,希望吸引更多的研究人员加入到这一新技术的研究队伍中来。