质子治疗装置动态电源控制系统研发

针对质子治疗装置中主环动态电源多平台能量的引出需求,研制了基于开源平台的高速实时动态电源控制系统,该控制系统以开源平台Beaglebone作为顶层硬件接口,以现场可编程逻辑门阵列(FPGA)为核心的控制器作为底层硬件接口,采用分布式的实验物理及工业控制系统(EPICS)进行远程控制。该系统可实时传输任意动态电源的输出参考电流波形数据,并结合定时系统与联锁系统,控制动态电源按预设电流波形进行输出,并实现多平台能量的引出。实验结果显示该控制系统能实现每秒最高十万条指令传输,百万次数据传输零误码率。同时,该系统结构灵活、扩展性强,可作为通用控制平台。     

细胞表面壳化的研究进展

细胞表面壳化主要是通过物理、化学等技术方法对细胞表面进行修饰,形成完整均匀的有机、无机、金属纳米粒子或者复合壳层结构,从而使不能自身壳化的生物细胞表面形成保护壳甚至赋予细胞新的功能,使细胞具备多功能性。近年来,此技术在细胞存储、细胞运输、细胞传感器、细胞芯片以及细胞治疗等方面应用广泛,发展迅速。本文综合目前的研究现状,详细介绍了可进行细胞表面壳化的细胞类型、生物表面壳化的方法以及人造细胞外壳的工程技术在生物医学以及能源环境中的应用等。     

Supramolecular Phthalocyanine Assemblies for Improved Photoacoustic Imaging and Photothermal Therapy

Phototheranostic nanoplatforms are of particular interest for cancer diagnosis and imaging‐guided therapy. Herein, we develop a supramolecular approach to fabricate a nanostructured phototheranostic agent through the direct self‐assembly of two water‐soluble phthalocyanine derivatives, PcS4 and PcN4. The nature of the molecular recognition between PcS4 and PcN4 facilitates the formation of nanostructure (PcS4‐PcN4) and consequently enables the fabrication of PcS4‐PcN4 with completely quenched fluorescence and reduced singlet oxygen generation, leading to the high photoacoustic and photothermal activity of PcS4‐PcN4. In vivo evaluations suggest that PcS4‐PcN4 could not only efficiently visualize a tumor with high contrast through whole‐body photoacoustic imaging but also enable excellent photothermal therapy for cancer.     

The glucocorticoid derivative with the phthalimide group cationic nanocrystal for ophthalmic application: a design space development approach

The glucocorticoid derivative of budesonide with a phthalimide group is a drug candidate to treat inflammatory eye diseases; nevertheless, it presents low water solubility. Drug nanocrystals have been proposed to overcome this hurdle. The development of an innovative ophthalmic anti-inflammatory nanosuspension was performed using a design space approach. We obtained the particle size reduction of this glucocorticoid derivative on a nanometer scale (approximately 165.0 nm), applying wet bead milling on a super reduced scale. The design of experiment supported the optimization of the formula evaluating the parameters that influence reducing the particle size and also allowed determining the design space. Considering the two statistical models developed and the size range obtained, we proposed that the optimized formulation for the glucocorticoid derivative nanosuspension may be 1.0 wt% glucocorticoid derivative and 0.092 wt% cetylpyridinium chloride. This formulation was characterized by the morphological, physical–chemical, and mucoadhesive in vitro test and showed potential for ophthalmic use with reduced frequency of product application, improved efficiency, and safety, which may promote better patient compliance.     

小分子基温敏聚合物纳米粒子的制备及在近红外二区荧光成像与光热治疗中的应用

以有机小分子4,9-二(5-9H-芴-2-基-噻吩-2-基)-6',7-联苯[1,2,5]噻二唑并[3,4-g]喹喔啉(TQF)为前驱体, 通过化学方法将其修饰为可引发可逆加成-断裂链转移聚合(RAFT)反应的小分子链转移剂TQF-苯基硫代链 转移剂（CTA）. 以TQF-CTA为链转移剂, 以偶氮二异丁腈为引发剂, 引发N-异丙基丙烯酰胺(NIPAAm)和 甲基丙烯酸寡聚乙二醇酯(OEGMA)发生RAFT聚合反应, 合成了具有良好水溶性和较低临界溶解温度(LCST)的小分子基共聚物[TQF-P(NIPAAm-co-OEGMA), TPNO]. 将其直接溶于水中可制备成温敏的球形纳米粒子 TPNO NPs. 研究结果表明, TPNO NPs在温度大于LCST(35 ℃)时表现出一个明显的粒径变化和显著的荧光 增强行为(2.2倍), 并成功实现了对活体小鼠血管与肿瘤的明亮近红外二区(NIR-Ⅱ)荧光成像(FI). 同时, TPNO NPs有着良好的光热转换效率(PCE=29.8%), 通过体外细胞实验证明了其对细胞具有较好的光热治疗(PTT)效果.     

硫代部花菁类染料生物成像及诊疗的研究进展

硫代部花菁是氮杂环阳离子和末端氨基、 羟基或烷氧基通过π共轭桥连在一起的一类荧光染料, 具有优异的光学性质和生物相容性, 其近红外发射优势以及光敏特性使以硫代部花菁为骨架的荧光探针和诊疗试剂在荧光/光声成像和肿瘤治疗方面发挥着重要作用. 本文综合评述了基于硫代部花菁构建的荧光探针和诊疗分子在识别各种生命或环境分析物以及光基疗法中的研究及应用, 讨论了该领域面临的问题, 并对未来的发展趋势进行了展望.     

基于框架核酸的细胞表面受体配体相互作用研究进展

细胞表面受体与配体之间的特异性相互作用在细胞生物学过程中起着重要作用。然而,与均相溶液不同,受体分子在细胞膜上的分布是非连续的、动态的,因此细胞表面的受体配体相互作用通常呈现复杂的非线性结合模式。框架核酸作为一类具有确定几何形状的DNA纳米支架,可用于多价配体的偶联,为深入揭示受体配体相互作用机制提供了可靠的工具。利用框架核酸纳米分辨率的可寻址特性,可实现对配体数目、间距及空间构象等参数的精确调控,进而研究细胞表面受体配体的结合特性及影响因素,优化结合条件最终实现高效的分子识别及靶向治疗。本文综述了基于框架核酸的细胞表面受体配体相互作用研究进展,通过探讨细胞表面受体配体相互作用的重要影响因素及生物学应用,对该研究领域的发展前景和未来趋势予以展望。     

Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione Obtained By Employing a Nano‐MOF with CuII as the Active Center

In photodynamic therapy (PDT), the level of reactive oxygen species (ROS) produced in the cell directly determines the therapeutic effect. Improvement in ROS concentration can be realized by reducing the glutathione (GSH) level or increasing the amount of photosensitizer. However, excessive amounts photosensitizer may cause side effects. Therefore, the development of photosensitizers that reduce GSH levels through synergistically improving ROS concentration in order to strengthen the efficacy of PDT for tumor is important. We report a nano‐metal–organic framework (Cu^II‐metalated nano‐MOF {CuL‐[AlOH]₂}_n (MOF‐2, H₆L=mesotetrakis(4‐carboxylphenyl)porphyrin)) based on Cu^II as the active center for PDT. This MOF‐2 is readily taken up by breast cancer cells, and high levels of ROS are generated under light irradiation. Meanwhile, intracellular GSH is considerably decreased owing to absorption on MOF‐2; this synergistically increases ROS concentration and accelerates apoptosis, thereby enhancing the effect of PDT. Notably, based on the direct adsorption of GSH, MOF‐2 showed a comparable effect with the commercial antitumor drug camptothecin in a mouse breast cancer model. This work provides strong evidence for MOF‐2 as a promising new PDT candidate and anticancer drug.     

铂类抗癌药物的多功能纳米递送体系

以顺铂为代表的小分子铂类抗癌药物是临床应用的一线化疗药物,但其严重的毒副作用和难以克服的耐药性限制了铂类药物的临床应用和研发。运用纳米药物递送技术可以实现药物的靶向递送和可控释放,来提高药物的生物利用度,降低药物的毒副作用以及耐药性,为癌症的治疗带来新的希望。此外,丰富多样的纳米递送体系易于实现药物与具有生物学活性试剂的共运输,从而为各种治疗策略以及诊疗策略的联用提供可能,为最终实现癌症的精准治疗展现广阔前景。本文从靶向递药、药物可控释放、联合治疗、诊疗一体化四个方面对铂类抗癌药物的多功能纳米递送体系在癌症治疗中的最新研究进展进行综述,同时通过列举最新研究成果,展示了新材料、新技术以及新颖设计思想在铂基纳米递送体系中的应用。     

Poly(ethylene glycol)‐crosslinked fullerenes for high efficient phototherapy

Poly(ethylene glycol)‐crosslinked multimeric C₆₀ was developed for use in photothermal/photodynamic therapy of malignant cells. We showed that: (i) the tumor surface temperature on KB tumor‐bearing nude mice treated with multimeric C₆₀ reached about 44 °C; (ii) this hyperthermic condition and tremendous singlet oxygen generation from multimeric C₆₀ resulted in significant tumor volume regression in KB tumor‐bearing nude mice; and (iii) multimeric C₆₀ also efficiently inhibited arthritic progress in the arthritis‐induced DBA/1 J mice model. This multimeric C₆₀ may be useful for photothermal/photodynamic cell ablation in various malignant cells. Copyright © 2012 John Wiley & Sons, Ltd.