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1、新型纳米材料用于难溶抗癌药物的靶向输送新型纳米材料用于难溶抗癌药物的靶向输送新型纳米材料用于难溶抗癌药物的靶向输送近年来，科研人员采用高通量筛选技术筛选出了大量应用于抗肿瘤的活性化合物，但这些化合物大多分子量高、疏水性强。据统计，目前至少有 40的药物因难溶性问题使用受到了限制。例如，紫杉醇是最具疗效的广谱抗肿瘤药物之一，但由于其水溶性差，临床上多以聚氧乙烯蓖麻油和乙醇混合物作为溶媒溶解后静脉注射进行给药。而此类给药方式会使药物分布于患者全身，引起毒副作用，同时有机溶剂的引入也会导致严重的过敏反应。Figure 1. Cellular uptake of PTX after treating
2、A549 cells with different PTX formulations for 12 h (a). The corresponding CLSM images on the right penal showing the uptake of PTXPMNTs without (b) and with (c) a magnetic field. Data represent averages, with error bars being standard deviations from three independent experiments performed in tripl
3、icate. Scale bars: 10 ? m.为解决这一难题，生化室马光辉课题组构建了一种基于磁性氧化铁纳米管的传输体系，实现了难溶抗癌药物紫杉醇的靶向输送和高效给药。通过对结晶过程的控制，可以将紫杉醇纳米晶成功地装载于纳米管内部。该体系不仅可以借助表面修饰的亲水性分子躲避内皮网状系统的识别，在体内具有较长的循环半衰期；而且能够在外加磁场的作用下展示出良好的磁靶向性，大大提高肿瘤细胞对药物的摄取量；上述纳米管在被细胞摄取后还会被溶酶体捕获，其中酸性环境能够促进氧化铁基质的降解，从而加速了难溶药物的释放。基于上述优势，该给药体系与传统商品化制剂相比显示出了更好的抗肿瘤能力和更少的毒副作用，
4、在难溶性抗肿瘤药物输送领域具有广阔的应用前景。相关结果作为封面文章发表在 Advanced Functional Materials 杂志上（Zhanguo Yue, Wei Wei, Zuoxiang You, Qinzheng Yang, Hua Yue, Zhiguo Su, and Guanghui Ma. Iron Oxide Nanotubes for Magnetically Guided Delivery and pH-Activated Release of Insoluble Anticancer Drugs. Adv. Funct. Mater. 2011, 21, 34
5、46） 。马光辉研究员带领的研究团队还在壳聚糖纳米粒子作为药物输送载体研究方面取得突破性进展。壳聚糖纳米球由于具有优越的生物兼容性、生物降解性和生物粘附性，在药物输送、组织工程和医学成像领域具有广阔的应用前景。近期研究发现，颗粒的理化性质与后续的细胞生物学效应密切相关。为了更加合理高效地应用壳聚糖纳米球，本课题组系统研究了表面电荷对细胞内吞行为及细胞内定位的影响。利用 SPG 膜乳化技术和表面沉积方法，成功制得出三种不同表面电荷的壳聚糖纳米球（N-NPs, = -45.842.18 mV; M-NPs, = 0.511.31 mV; P-NPs, =39.252.68 mV） 。在多种细胞系中
6、，壳聚糖纳米球的内吞速率及内吞量都和其表面电荷呈正相关性。进一步的细胞内定位表明，N-NPs 和 M-NPs 定位于溶酶体内；而 P-NPs 能够逃逸出溶酶体，并在核周分布。该结论为壳聚糖纳米球的设计和应用提供了重要的理论基础。相关结果发表在美国化学学会主办的刊物 Biomacromolecules 上（Zhanguo Yue, Wei Wei, Piping LV, Hua Yue, Lianyan Wang, Zhiguo Su, and Guanghui Ma. Biomacromolecules, 2011, 12：2440-2446)。该团队吴颉、王连艳、苏志国和马光辉老师老师共同发
7、表在Biomaterials 杂志上论文（Jie Wu, Wei Wei, Lianyan Wang, Zhiguo Su, Guanghui Ma. A Thermosensitive Hydrogel Based on Quaternized Chitosan and Poly(ethylene glycol) for Nasal Drug Delivery Systems. Biomaterials., 28(13), 2220-2232, 2007）还于 2011 年入选“Biomaterials 杂志 2006-2010 年 Top 50最高引用中国大陆论文“（Biomaterial
8、s Top 50 Highly Cited Articles By Chinese Mainland Authors 2006 - 2010） ，该奖项是由国际著名 Elsevier 出版集团根据Biomaterials期刊中发表文章在 SCI 数据库的他引次数评选出的。该论文自发表至今受到了国内外的广泛关注，截止目前已被引用 44 次，他引 43 次。上述研究成果得到了 973 项目（2009CB930300） ，国家自然科学基金（20820102036）和国家科技重大专项（2009 ZX09503-027）的共同资助。 2011 年该团队发表的 SCI 论文：(1) Yueling Zha
9、ng, Wei Wei, Piping Lv, Lianyan Wang, Zhiguo Su, Guanghui Ma. Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin. European Journal of Pharmaceutics and Biopharmaceutics. 2011, 77(1): 11-19. (SCI IF 4.304)(2) Zhanguo Yue, Wei Wei, Zuoxiang You, Qinzheng Yang, Hu
10、a Yue, Zhiguo Su, Guanghui Ma. Iron Oxide Nanotube for Magnetically Guided Delivery and pH Activated-Release of Insoluble Anticancer Drugs. Advanced Functional Materials. 2011, 21(18): 3446-3453. (SCI IF 8.508)(3) Ying Zhang, Fei Gao, Song-Ping Zhang, Zhiguo Su, Guanghui Ma, Ping Wang. Simultaneous
11、production of 1,3-dihydroxyacetone and xylitol from glycerol and xylose using a nanoparticle-supported multi-enzyme system with in situ cofactor regeneration. Bioresource Technology. 2011, 102(2): 1837-1843. (SCI IF 4.365)(4) Zhanguo Yue, Wei Wei, Piping LV, Hua Yue, Lianyan Wang, Ma Guanghui. Surfa
12、ce Charge Affects Cellular Uptake and Intracellular Trafficking of Chitosan-based Nanoparticles. Biomacromolecules. 2011, 12 (7): 2440-2446. (SCI IF 5.327)(5) Yi Wei, Yuxia Wang Lianyan Wang, Dongxia Hao, Zhiguo Su, Guanghui Ma. Fabrication strategy for amphiphilic microcapsules with narrow size dis
13、tribution by premix membrane emulsification. Colloids and Surfaces B: Biointerfaces. 2.11, 87: 399- 408. (SCI IF 2.78)(6) Yi Wei, Yu-Xia Wang, Wei Wang, Sa V. Ho, Wei Wei, Zhiguo Su, Guanghui Ma. mPEG-PLA Microspheres with Narrow Size Distribution Increase the Controlled Release Effect of Recombinan
14、t Human Growth Hormone. J. Mater. Chem. 2011, 21: 12691-12699. (SCI IF5.101)(7) Weiqing Zhou, Juan Li, Wei Wei, Zhiguo Su, Guanghui Ma. Effect of solubilization of surfactant aggregates on pore structure in gigaporous polymeric particles. Colloids and Surfaces A: Physicochem. Eng. Aspects. 2011, 384
15、: 549-554. (SCI IF 2.13)(8) Jian-Bo Qu, Yong-Dong Huang, Guang-Lun Jing, Jian-Guo Liu, Wei-Qing Zhou, Hu Zhu. A novel matrix derivatized from hydrophilic gigaporous polystyrene-based microspheres for high-speed immobilized-metal affinity chromatography. Journal of Chromatography B. 2011, 879: 1043-1
16、048. (SCI IF 2.971)(9) Yueling Zhang, Xingyuan Jia, Lianyan Wang, Jingzhong Liu, Zhiguo Su, Guanghui Ma. Preparation of Ca-Alginate Microparticles and Its Application for Phenylketonuria Oral Therapy. Industrial and Engineering Chemistry Research. 2011, 50 (7): 4106-4112. (SCI IF 2.207)(10) Tianbao Si, Yuxia Wang, Wei Wei, Pingping Lv, Zhiguo Su, Guanghui Ma. Effect of acrylic acid weight percentage on the pore size in poly(N-Isopropyl acrylamide-co-acrylic acid) microspheres. React.
