摘要
聚酰胺-胺(polyamidoamine,PAMAM)树枝形分子是一种20世纪80年代中期人工合成的特殊结构的新型纳米级高分子化合物,呈辐射状对称的球体结构。与传统高分子相比,PAMAM具有对称、高度支化、单分散、精确的分子结构、易控的纳米尺寸等多种独特性质。PAMAM表面具有大量可修饰的官能团,内部具有大量空腔,且水溶性好,这些特点使PAMAM在催化剂载体、药物和基因载体、纳米材料合成模板等领域取得了广泛的应用。这些树枝形分子的应用大部分是以树枝形分子为主体,通过非共价作用结合客体分子来实现的,目前树枝形分子的主-客体相互作用研究已经发展成为高分子物理化学领域的研究热点。
本文主要利用核磁共振波谱,对树枝形分子与客体分子的相互作用进行研究,重点关注的是树枝形分子与客体分子的结合动力学、结合位点、内部包裹和外表结合的转换等方面。主要研究工作及结论介绍如下；
(1)应用1H-NMR, diffusion以及NOE核磁共振技术对PAMAM树枝形分子与表面活性剂十二烷基硫酸钠(SDS)之间的相互作用机制进行了详细的研究。结果表明随着SDS的加入,树枝形分子与SDS之间形成不同形态的聚集体,低SDS浓度时的主要形成包合物结构,中间浓度时SDS以脂双层形式与PAMAM树枝形分子表面结合,高浓度条件下,SDS以胶团形式与树枝形分子结合并形成超分子结构。1H-NMR对PAMAM/SDS的主-客体结合动力学分析表明,PAMAM-SDS聚集体结构中存在快交换与慢交换的转换,NOE结果验证了SDS装载在PAMAM内部空腔形成包合物结构,PAMAM与SDS分子之间的相互作用力包括PAMAM内部空腔与SDS烷基链之间的疏水相互作用以及PAMAM表面与SDS单体或胶团之间的静电或氢键相互作用。
(2)应用NOE NMR方法研究了构成DNA/RNA的基本单元单磷酸鸟苷(GMP)与PAMAM树枝形分子之间的相互作用,获得了GMP分子在G5PAMAM中的确切的结合定位信息。结果表明GMP在树枝形分子表面以及内部空腔之间存在结合平衡。并且这种结合平衡收到溶液酸碱度的调控：碱性条件下,GMP主要结合在树枝形分子的表面；中性条件或弱酸性条件下GMP可以进入树枝形分子的内部空腔；而在强酸性条件下,GMP以游离态的形式存在于体系中不与主体结合。这种结合/封装的转换主要依赖于树枝形分子表面和内部的电荷密度,以及客体分子的带电状态。
(3)应用1H-NMR以及NOE核磁共振方法研究了完全乙酰化的PAMAM树枝形分子与携带多个电荷的客体分子如刚果红(CR)及吲哚菁绿(ICG)之间的相互作用。表面为伯胺基团的阳离子PAMAM树枝形分子与CR或ICG在溶液中形成交联的超分子结构,产生沉淀,而乙酰化修饰的树枝形分子可以避免这种不稳定的复合物的形成。NOE核磁共振结果表明在弱酸性条件下,乙酰化的树枝形分子与CR和ICG能形成稳定的复合物,乙酰化的树枝形分子具有较强的包裹携带多个电荷且分子量较大的客体分子的能力。UV-Vis-NIR研究进一步验证了乙酰化的树枝形分子能显著提高ICG水溶液的光稳定性,抑制ICG的J型聚集体的形成。
这些研究表明核磁共振在研究树枝形分子的主-客体相互作用过程中是一种灵敏,高效,便捷的方法；为树枝形分子的主—客体系统提供了新的物理化学视角以及新的研究思路；同时,通过本文的研究,也为基于树枝形分子的药物输送系统的设计奠定了重要的理论支持。
Polyamidoamine (PAMAM) dendrimers is a new class of artificial polymers with nano-scale size and symmetrical globular shape which are synthesized by Tomalia in1985. Compared to the traditional polymers, PAMAM dendrimer has several unique properties such as symmetrical, well-defined and hyperbranched structure, extremely low polydispersity, well-defined size, well solubility, multiple hollow relative non-polar cavities and number of peripheral groups. Due to these structural properties, PAMAM dendrimers have been widely applied in many fields include catalyst, drug and gene delivery, and the template of the nanopartical synthesis. These applications of PAMAM dendrimer are based on the non-covalent host-guest interactions between dendrimers and guest molecules. Nowadays, the study of the host-guest interaction based on PAMAM dendrimer is a hotspot in the polymeric chemistry and physics fields.
In this dissertation, the host-guest interactions between PAMAM dendrimer and guest molecules are investigated by the nuclear magnetic response (NMR) techniques. The focuses of this dissertation are the binding kinetics between dendrimer and the guests, the binding sites, the surface binding/encapsulation transitions and the structure of the aggregates. The main research works and conclusions are organized as followings:
(1) The detailed interaction mechanisms between PAMAM dendrimer and surfactants (sodium dodecyl sulfate, SDS) in aqueous solutions are investigated by a combination of1H-NMR, diffusion measurements (PFG), and NOE techniques. The diffusion studies suggested that different types of dendrimer-surfactant aggregates were formed by varying the surfactant concentrations in the dendrimer solution. A inclusion structure is formed at a low SDS concentration. With the addition of the SDS, the bilayer micelles of SDS are formed and binded at the surface of PAMAM dendrimer and the supermolecular aggregates are formed at last. The1H NMR analysis for the binding kinetics between dendrimer and the guests further proved the presence of fast exchange/slow exchange transitions in the dendrimer-surfactant aggregates. The formation of molecular inclusions in the dendrimer/SDS complex is concluded by the NOE measurements. The supramolecular structure of the aggregate was based on the hydrophobic interactions between the dendrimer scaffold and the surfactant aliphatic chain, as well as electrostatic/hydrogen-bond interactions between dendrimers and SDS monomers, bilayer or globular micelles.
(2) The interaction between G5PAMAM dendrimer and the guano sine monophosphate (GMP) which is a basic unit of DNA and RNA, is investigated by NOE NMR techniques and the precise information of the binding sites between PAMAM dendrimer and GMP molecules is obtained. The NOE results indicated that a balance occurs between the surface binding of GMP on the dendrimer and the encapsulation in the cavities of dendrimer and this balance is controlled by the solution pH value. The GMP molecules are binding on the surface of dendrimers in the basic solutions, and the encapsulation of the GMP by the dendrimer cavities occurs at the neutral and mild acidic conditions. GMP molecules are in a free-state and do not bind with host molecules in the strong acidic solution. The binding/encapsulation transitions are depended on the surface and interior charge densities of the dendrimer and the charged state of the guest molecules.
(3) The NMR techniques including1H NMR and1H-1H NOESY are used to characterize the host-guest interaction between fully acetylated PAMAM dendrimers and the congo red (CR) and indocyanine green (ICG) molecules bearing multiple. The cationic PAMAM dendrimers with amine groups at their surfaces are found to form precipitate with CR and ICG, but acetylated PAMAM dendrimers avoid the formation of cross-linking structures in aqueous solutions. NOESY studies revealed that the stable complexes are formed between acetylated dendrimers and CR/ICG at the mild acidic conditions and acetylated dendrimers show much stronger ability to encapsulate the guest molecules with multiple charges and large molecular weight than cationic ones. Also, UV-Vis-NIR studies suggested that acetylated dendrimers significantly improve the photo-stability of indocyanine green and prevent the formation of indocyanine green J-aggregates in aqueous solutions.
These results show that NMR technique is a sensitive, high-efficiency and convenient method for the investigation of the intermolecular interaction between dendrimers and guests, and can provide a new physical-chemical view and a new idea for the host-guest system of the dendrimers. This research can also give some important theoretical supports for the drug delivery development based on dendrimers.
引文
Agarwal, A., S. Saraf, A. Asthana, U. Gupta, V. Gajbhiye and N. K. Jain (2008). "Ligand based dendritic systems for tumor targeting." International Journal of Pharmaceutics 350(1-2): 3-13.
Aharoni, S. M., C. R. Crosby and E. K. Walsh (1982). "Size and solution properties of globular tert-butyloxycarbonyl-poly(α,iε-L-lysine)." Macromolecules 15(4):1093-1098.
Bakshi, M. S. and A. Kaura (2005). "Fluorescence studies of interactions of ionic surfactants with poly (amidoamine) dendrimers." Journal of Colloid and Interface Science 284(2): 680-686.
Baxter, N. J., T. H. Lilley, E. Haslam and M. P. Williamson (1997). "Multiple interactions between polyphenols and a salivary proline-rich protein repeat result in complexation and precipitation." Biochemistry 36:5566-5577.
Boisselier, E., C. Ornelas, I. Pianet, J. R. Aranzaes and D. Astruc (2008). "Four generations of water-soluble dendrimers with 9 to 243 benzoate tethers:Synthesis and dendritic effects on their ion pairing with acetylcholine, benzyltriethylammonium, and dopamine in water." Chemistry-a European Journal 14(18):5577-5587.
Boris, D. and M. Rubinstein (1996). "A self-consistent mean field model of a starburst dendrimer: dense core vs dense shell." Macromolecules 29(22):7251-7260.
Bosman, A. W., H. M. Janssen and E. W. Meijer (1999). "About dendrimers:structure, physical properties, and applications." Chemical Reviews 99(7):1665-1688.
Brand, T., E. J. Cabrita and S. Berger (2005). "Intermolecular interaction as investigated by NOE and diffusion studies." Progress in Nuclear Magnetic Resonance Spectroscopy 46(4): 159-196.
Broeren, M. A. C., B. F. M. de Waal, M. H. P. van Genderen, H. M. H. F. Sanders, G. Fytas and E. W. Meijer (2005). "Multicomponent host-guest chemistry of carboxylic acid and phosphonic acid based guests with dendritic hosts:an NMR study." Journal of the American Chemical Society 127(29):10334-10343.
Caminade A., Laurent R. and Majoral J. (2005). "Characterization of dendrimers." Adv. Drug Delivery Rev.57(15):2130-2146.
Caminati, G., N. J. Turro and D. A. Tomalia (1990). "Photophysical investigation of starburst dendrimers and their interactions with anionic and cationic surfactants." Journal of the American Chemical Society 112(23):8515-8522.
Chai, M., Y. Niu, W. J. Youngs and P. L. Rinaldi (2000). "3D NMR studies of DAB-16 dendrimer." Macromolecules 33(15):5395-5398.
Chai, M., Y. Niu, W. J. Youngs and P. L. Rinaldi (2001). "Structure and conformation of DAB dendrimers in solution via multidimensional NMR techniques." Journal of the American Chemical Society 123(20):4670-4678.
Chai, M. H., A. K. Holley and M. Kruskamp (2007). "Encapsulating fluorescein using adipic acid self-assembly on the surface of PPI-3 dendrimer." Chemical Communications(2): 168-170.
Chauhan, A. S., N. K. Jain, P. V. Diwan and A. J. Khopade (2004). "Solubility enhancement of indomethacin with poly(amidoamine) dendrimers and targeting to inflammatory regions of arthritic rats." Journal of Drug Targeting 12(9-10):575-583.
Cheng, Y., Y. Li, Q. Wu and T. Xu (2008). "New insights into the interactions between dendrimers and surfactants by two dimensional NOE NMR spectroscopy." The Journal of Physical Chemistry B 112(40):12674-12680.
Cheng, Y., Q. Wu, Y. Li and T. Xu (2008). "External electrostatic interaction versus internal encapsulation between cationic dendrimers and negatively charged drugs:which contributes more to solubility enhancement of the drugs?" The Journal of Physical Chemistry B 112(30):8884-8890.
Cheng, Y. Y., L. B. Zhao, Y. W. Li and T. W. Xu (2011). "Design of biocompatible dendrimers for cancer diagnosis and therapy:current status and future perspectives." Chemical Society Reviews 40(5):2673-2703.
Choi, Y., A. Mecke, B. G. Orr, M. M. Banaszak Holl and J. R. Baker (2004). "DNA-directed synthesis of generation 7 and 5 PAMAM dendrimer nanoclusters." Nano Letters 4(3): 391-397.
Cohen, Y., L. Avram and L. Frish (2005). "Diffusion NMR spectroscopy in supramolecular and combinatorial chemistry:an old parameter—new insights." Angewandte Chemie International Edition 44(4):520-554.
Cram, D. J. (1988). "The design of molecular hosts, guests, and their complexes (Nobel lecture)." Angewandte Chemie-International Edition in English 27(8):1009-1020.
D'Emanuele, A. and D. Attwood (2005). "Dendrimer-drug interactions." Advanced Drug Delivery Reviews 57(15):2147-2162.
D'Emanuele, A., R. Jevprasesphant, J. Penny and D. Attwood (2004). "The use of a dendrimer-propranolol prodrug to bypass efflux transporters and enhance oral bioavailability." Journal of Controlled Release 95(3):447-453.
de Brabander-van den Berg, E. M. M. and E. W. Meijer (1993). "Poly(propylene imine) dendrimers:large-scale synthesis by hetereogeneously catalyzed hydrogenations." Angewandte Chemie International Edition in English 32(9):1308-1311.
Diercks, T., M. Coles and H. Kessler (2001). "Applications of NMR in drug discovery." Current Opinion in Chemical Biology 5(3):285-291.
Dietrich, B., M. W. Hosseini, J. M. Lehn and R. B. Sessions (1981). "Anion recept of molecules-synthesis and anion-binding properties of polyammonium macrocyles." Journal of the American Chemical Society 103(5):1282-1283.
Dufes, C., I. F. Uchegbu and A. G. Schatzlein (2005). "Dendrimers in gene delivery." Advanced Drug Delivery Reviews 57(15):2177-2202.
Duncan, R. and L. Izzo (2005). "Dendrimer biocompatibility and toxicity." Advanced Drug Delivery Reviews 57(15):2215-2237.
Dykes, G. M., D. K. Smith and A. Caragheorgheopol (2004). "NMR and ESR investigations of the interaction between a carboxylic acid and an amine at the focal point of 1-lysine based dendritic branches." Organic & Biomolecular Chemistry 2(6):922-926.
Emsley, J. W. and J. Feeney (2007). "Forty years of progress in nuclear magnetic resonance spectroscopy." Progress in Nuclear Magnetic Resonance Spectroscopy 50(4):179-198.
Esfand, R. and D. A. Tomalia (2001). "Poly(amidoamine) (PAMAM) dendrimers:from biomimicry to drug delivery and biomedical applications." Drug Discovery Today 6(8): 427-436.
Esumi, K., K. Kuwabara, T. Chiba, F. Kobayashi, H. Mizutani and K. Torigoe (2002). "Interactions between a hydrophobically modified poly(amidoamine)dendrimer and surfactants in aqueous solutions." Colloids and Surfaces a-Physicochemical and Engineering Aspects 197(1-3):141-146.
Fant, K., E. K. Eshjorner, A. Jenkins, M. C. Grossel, P. Lincoln and B. Norden (2010). "Effects of PEGylation and acetylation of PAMAM dendrimers on DNA binding, cytotoxicity and in vitro rransfection efficiency." Molecular Pharmaceutics 7(5):1734-1746.
Fielding, L. (2007). "NMR methods for the determination of protein-ligand dissociation constants " Progress in Nuclear Magnetic Resonance Spectroscopy 51:219-242.
Ghoreishi, S. M., Y. Li, J. F. Holzwarth, E. Khoshdel, J. Warr, D. M. Bloor and E. Wyn-Jones (1999). "The interaction between nonionic dendrimers and surfactants electromotive force and microcalorimetry studies." Langmuir 15(6):1938-1944.
Gillies, E. R. and J. M. J. Frechet (2005). "Dendrimers and dendritic polymers in drug delivery." Drug Discovery Today 10(1):35-43.
Gupta, U., H. B. Agashe, A. Asthana and N. K. Jain (2006). "Dendrimers:novel polymeric nanoarchitectures for solubility enhancement." Biomacromolecules 7(3):649-658.
Handel, H., E. Gesele, K. Gottschall and K. Albert (2003). "Application of HRMAS 1H NMR spectroscopy to investigate interactions between ligands and synthetic receptors." Angewandte Chemie International Edition 42(4):438-442.
Hawker, C. J. and J. M. J. Frechet (1990). "Preparation of polymers with controlled molecular architecture-a new convergent approach to dendritic macramolecules." Journal of the American Chemical Society 112(21):7638-7647.
Herweijer, H. and J. A. Wolff (2003). "Progress and prospects:naked DNA gene transfer and therapy." Gene Ther 10(6):453-458.
Hu, J., Y. Cheng, Q. Wu, L. Zhao and T. Xu (2009). "Host-guest chemistry of dendrimer-drug complexes.2. effects of molecular properties of guests and surface functionalities of dendrimers." The Journal of Physical Chemistry B 113(31):10650-10659.
Hu, J. J., Y. Z. Su, H. F. Zhang, T. W. Xu and Y. Y. Cheng (2011). "Design of interior-functionalized fully acetylated dendrimers for anticancer drug delivery.' Biomaterials 32(36):9950-9959.
Jackson, C. L., H. D. Chanzy, F. P. Booy, B. J. Drake, D. A. Tomalia, B. J. Bauer and E. J. Amis (1998). "Visualization of dendrimer molecules by transmission electron microscopy (TEM):staining methods and Cryo-TEM of vitrified solutions." Macromolecules 31(18): 6259-6265.
Jain, K., P. Kesharwani, U. Gupta and N. K. Jain (2010). "Dendrimer toxicity:let's meet the challenge." International Journal of Pharmaceutics 394(1-2):122-142.
Jain, N. K. and U. Gupta (2008). "Application of dendrimer-drug complexation in the enhancement of drug solubility and bioavailability." Expert Opinion on Drug Metabolism & Toxicology 4(8):1035-1052.
Jensen, L. B., K. Mortensen, G. M. Pavan, M. R. Kasimova, D. K. Jensen, V. Gadzhyeva, H. M. Nielsen and C. Foged (2010). "Molecular characterization of the interaction between siRNA and PAMAM G7 dendrimers by SAXS, ITC, and molecular dynamics simulations." Biomacromolecules 11(12):3571-3577.
Khopade, A. J. and F. Caruso (2002). "Stepwise self-assembled poly(amidoamine) dendrimer and poly(styrenesulfonate) microcapsules as sustained delivery vehicles." Biomacromolecules 3(6):1154-1162.
Kirchherr, A. K., A. Briel and K. Mader (2009). "Stabilization of indocyanine green by encapsulation within micellar systems." Molecular Pharmaceutics 6(2):480-491.
Kitchens, K., A. Foraker, R. Kolhatkar, P. Swaan and H. Ghandehari (2007). "Endocytosis and interaction of poly (amidoamine) dendrimers with Caco-2 cells." Pharmaceutical Research 24(11):2138-2145.
Kleinman, M. H., J. H. Flory, D. A. Tomalia and N. J. Turro (2000). "Effect of protonation and PAMAM dendrimer size on the complexation and dynamic mobility of 2-naphthol." The Journal of Physical Chemistry B 104(48):11472-11479.
Kolhatkar, R. B., K. M. Kitchens, P. W. Swaan and H. Ghandehari (2007). "Surface acetylation of polyamidoamine (PAMAM) dendrimers decreases cytotoxicity while maintaining membrane permeability." Bioconjugate Chemistry 18(6):2054-2060.
Kubat, P., K. Lang, P. Janda and P. Anzenbacher (2005). "Interaction of porphyrins with a dendrimer template:self-aggregation controlled by pH." Langmuir 21(21):9714-9720.
Lescanec, R. L. and M. Muthukumar (1990). "Configurational characteristics and scaling behavior of starburst molecules:a computational study." Macromolecules 23(8):2280-2288.
Li, X. F., A. Kroeger, T. Azzam and A. Eisenberg (2008). "Dendrimer influenced supramolecular structure formation-of block copolymers:II. Dendrimer concentration dependence." Langmuir 24(6):2705-2711.
Li, Y., D. M. Bloor and E. Wyn-Jones (1996). "Polymer/surfactant interactions. the controlled desorption of sodium dodecyl sulfate (SDS) from a polymer/SDS complex in aqueous solution." Langmuir 12(18):4476-4478.
Lim, Y. B., T. Kim, J. W. Lee, S. M. Kim, H. J. Kim, K. Kim and J. S. Park (2002). "Self-assembled ternary complex of cationic dendrimer, cucurbituril, and DNA: Noncovalent strategy in developing a gene delivery carrier." Bioconjugate Chemistry 13(6):1181-1185.
Ma, J.-h., C. Guo, Y.-1. Tang, H. Zhang and H.-z. Liu (2007). "Probing paeonol-pluronic polymer interactions by 1H NMR spectroscopy." The Journal of Physical Chemistry B 111(47): 13371-13378.
Majoros, I. J., B. Keszler, S. Woehler, T. Bull and J. R. Baker (2003). "Acetylation of poly(amidoamine) dendrimers." Macromolecules 36(15):5526-5529.
Mansfield, M. L. and L. I. Klushin (1993). "Monte Carlo studies of dendrimer macromolecules." Macromolecules 26(16):4262-4268.
Mintzer, M. A. and M. W. Grinstaff (2011). "Biomedical applications of dendrimers:a tutorial." Chemical Society Reviews 40(1):173-190.
Mitra, A. and T. Imae (2004). "Nanogel formation consisting of DNA and poly(amido amine) dendrimer studied by static light scattering and atomic force microscopy.' Biomacromolecules 5(1):69-73.
Moreno-Bondi, M. C, G. Orellana, N. J. Turro and D. A. Tomalia (1990). "Photoinduced electron-transfer reactions to probe the structure of starburst dendrimers." Macromolecules 23(3):910-912.
Mourtzis N., Cordoyiannis G., Nounesis G. and Yannakopoulou K. (2003). "Single and double threading of congo red into cyclodextrin. solution structures and thermodynamic parameters of 1:1 and 2:2 adducts, as obtained form NMR spectroscopy and microcalorimetry." Supramol. Chem.15(7-8):639-649.
Najlah, M., S. Freeman, D. Attwood and A. D'Emanuele (2006). "Synthesis, characterization and stability of dendrimer prodrugs." International Journal of Pharmaceutics 308(1-2): 175-182.
Najlah, M., S. Freeman, D. Attwood and A. D'Emanuele (2007). "In vitro evaluation of dendrimer prodrugs for oral drug delivery." International Journal of Pharmaceutics 336(1):183-190.
Naylor, A. M., W. A. Goddard, G. E. Kiefer and D. A. Tomalia (1989). "Starburst dendrimers.5. molecular shape control." Journal of the American Chemical Society 111(6):2339-2341.
Newkome, G. R., Z. Q. Yao, G. R. Baker and V. K. Gupta (1985). "Micelles 1. cascade molecules-a new approach to micelles-a 27-arborol." Journal of Organic Chemistry 50(11): 2003-2004.
Orberg, M. L., K. Schillen and T. Nylander (2007). "Dynamic light scattering and fluorescence study of the interaction between double-stranded DNA and poly(amido amine) dendrimers." Biomacromolecules 8(5):1557-1563.
Orfi, L., M. F. Lin and C. K. Larive (1998). "Measurement of SDS micelle-peptide association using H-1 NMR chemical shift analysis and pulsed field gradient NMR spectroscopy.' Analytical Chemistry 70(7):1339-1345.
Ornelas, D. A. E. B. C. (2010). "Dendrimers designed for functions:from physical, photophysical, and supramolecular properties to applications in sensing, catalysis, molecular electronics, photonics, and nanomedicine." Chem. Rev.110:1857-1959.
Ottaviani, M. F., P. Andechaga, N. J. Turro and D. A. Tomalia (1997). "Model for the interactions between anionic dendrimers and cationic surfactants by means of the spin probe method." The Journal of Physical Chemistry B 101(31):6057-6065.
Pack, D. W., A. S. Hoffman, S. Pun and P. S. Stayton (2005). "Design and development of polymers for gene delivery." Nat Rev Drug Discov 4(7):581-593.
Pan, B., F. Gao, R. He, D. Cui and Y. Zhang (2006). "Study on interaction between poly(amidoamine) dendrimer and CdSe nanocrystal in chloroform." Journal of Colloid and Interface Science 297(1):151-156.
Pan, Z. H., P. Somasundaran, N. J. Turro and S. Jockusch (2004). "Interactions of cationic dendrimers with hematite mineral." Colloids and Surfaces 238:123-126.
Patil, M. L., M. Zhang, S. Betigeri, O. Taratula, H. He and T. Minko (2008). "Surface-modified and internally cationic polyamidoamine dendrimers for efficient siRNA delivery." Bioconjugate Chemistry 19(7):1396-1403.
Patil, M. L., M. Zhang, O. Taratula, O. B. Garbuzenko, H. He and T. Minko (2009). "Internally cationic polyamidoamine PAMAM-OH dendrimers for siRNA delivery:effect of the degree of quaternization and cancer targeting." Biomacromolecules 10(2):258-266.
Perez, A. P., E. L. Romero and M. J. Morilla (2009). "Ethylendiamine core PAMAM dendrimers/siRNA complexes as in vitro silencing agents." International Journal of Pharmaceutics 380(1-2):189-200.
Po, H. N. and N. M. Senozan (2001). "The Henderson-Hasselbalch equation:its history and limitations." Journal of Chemical Education 78(11):1499-1503.
Pregosin, P. S., P. G. A. Kumar and I. Fernandez (2005). "Pulsed gradient spin-echo (PGSE) diffusion and H-1,F-19 heteronuclear overhauser spectroscopy (HOESY) NMR methods in inorganic and organometallic chemistry:Something old and something new." Chemical Reviews 105(8):2977-2998.
Priyam, A., D. E. Blumling and K. L. Knappenberger (2010). "Synthesis, characterization, and self-organization of dendrimer-encapsulated HgTe quantum dots." Langmuir 26(13): 10636-10644.
Rodriguez, V. B., S. M. Henry, A. S. Hoffman, P. S. Stayton, X. D. Li and S. H. Pun (2008). "Encapsulation and stabilization of indocyanine green within poly(styrene-alt-maleic anhydride) block-poly(styrene) micelles for near-infrared imaging." Journal of Biomedical Optics 13(1).
S., S. (2009). "Dendrimers as versatile platform in drug delivery applications." Eur. J. Pharm. Biopharm.71(3):445-462.
Santo, M. and M. A. Fox (1999). "Hydrogen bonding interactions between Starburst dendrimers and several molecules of biological interest." Journal of Physical Organic Chemistry 12(4):293-307.
Saxena, V., M. Sadoqi and J. Shao (2004). "Enhanced photo-stability, thermal-stability and aqueous-stability of indocyanine green in polymeric nanoparticulate systems." Journal of Photochemistry and Photobiology B-Biology 74(1):29-38.
Schutz, A. K., A. Soragni, S. Hornemann, A. Aguzzi, M. Ernst, A. Bockmann and B. H. Meier (2011). "The amyloid-congo red interface at atomic resolution." Angewandte Chemie-International Edition 50(26):5956-5960.
Shcharbin, D., M. Szwedzka and M. Bryszewska (2007). "Does fluorescence of ANS reflect its binding to PAMAM dendrimer?" Bioorganic Chemistry 35(2):170-174.
Skowronek, M., B. Stopa, L. Konieczny, J. Rybarska, B. Piekarska, E. Szneler, G. Bakalarski and I. Roterman (1998). "Self-assembly of congo red-a theoretical and experimental approach to identify its supramolecular organization in water and salt solutions." Biopolymers 46(5):267-281.
Smith, P. E. S., J. R. Brender, U. H. N. Durr, J. Xu, D. G. Mullen, M. M. Banaszak Holl and A. Ramamoorthy (2010). "Solid-state NMR reveals the hydrophobic-core location of poly(amidoamine) dendrimers in biomembranes." Journal of the American Chemical Society 132(23):8087-8097.
Sonawane, N. D., F. C. Szoka and A. S. Verkman (2003). "Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes." Journal of Biological Chemistry 278(45):44826-44831.
Staples, E, I. Tucker, J. Penfold, N. Warren, R. K. Thomas and D. J. F. Taylor (2002). "Organization of polymer-surfactant mixtures at the air-water interface:sodium dodecyl sulfate and poly(dimethyldiallylammonium chloride)." Langmuir 18(13):5147-5153.
Sukul, D., S. K. Pal, D. Mandal, S. Sen and K. Bhattacharyya (2000). "Excited state proton transfer as a probe for polymer-surfactant interaction." The Journal of Physical Chemistry B 104(26):6128-6132.
Svenson, S. and D. A. Tomalia (2005). "commentary-dendrimers in biomedical applications reflections on the field." Advanced Drug Delivery Reviews 57(15):2106-2129.
Tam, K. C. and E. Wyn-Jones (2006). "Insights on polymer surfactant complex structures during the binding of surfactants to polymers as measured by equilibrium and structural techniques." Chemical Society Reviews 35(8):693-709.
Taratula, O., O. B. Garbuzenko, P. Kirkpatrick, I. Pandya, R. Savla, V. P. Pozharov, H. X. He and T. Minko (2009). "Surface-engineered targeted PPI dendrimer for efficient intracellular and intratumoral siRNA delivery." Journal of Controlled Release 140(3):284-293.
Tekade, R. K., P. V. Kumar and N. K. Jain (2008). "Dendrimers in oncology:an expanding horizon." Chemical Reviews 109(1):49-87.
Tomalia, D. A. (2005). "Birth of a new macromolecular architecture:dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry." Progress in Polymer Science 30(3-4):294-324.
Tomalia, D. A., H. Baker, J. Dewald, M. Hall, G. Kallos, S. Martin, J. Roeck, J. Ryder and P. Smith (1985). "A new class of polymers-starburst-dendritic macromolecules." Polymer Journal 17(1):117-132.
Tomalia, D. A., A. M. Naylor and W. A. Goddard (1990). "Starburst dendrimers:molecular-level control of size, shape, surface chemistry, topology, and flexibility from atoms to macroscopic matter." Angewandte Chemie International Edition in English 29(2): 138-175.
van Heerbeek, R., P. C. J. Kamer, P. van Leeuwen and J. N. H. Reek (2002). "Dendrimers as support for recoverable catalysts and reagents." Chemical Reviews 102(10):3717-3756.
Waite, C. L., S. M. Sparks, K. E. Uhrich and C. M. Roth (2009). "Acetylation of PAMAM dendrimers for cellular delivery of siRNA." Bmc Biotechnology 9.
Wang, C. and K. C. Tam (2002). "New insights on the interaction mechanism within oppositely charged polymer/surfactant systems." Langmuir 18(17):6484-6490.
Wang, C., E. Wyn-Jones, J. Sidhu and K. C. Tam (2007). "Supramolecular complex induced by the binding of sodium dodecyl sulfate to PAMAM dendrimers." Langmuir 23(4): 1635-1639.
Watkins, D. M., Y. Sayed-Sweet, J. W. Klimash, N. J. Turro and D. A. Tomalia (1997). "Dendrimers with hydrophobic cores and the formation of supramolecular dendrimer-surfactant assemblies." Langmuir 13(12):3136-3141.
Wenz, G. (1994). "Cycledextrins as building-blocks for supramolecular structures and functional units." Angewandte Chemie International Edition in English 33(8):803-822.
White, A. R., P. Enever, M. Tayebi, R. Mushens, J. Linehan, S. Brandner, D. Anstee, J. Collinge and S. Hawke (2003). "Monoclonal antibodies inhibit prion replication and delay the development of prion disease." Nature 422(6927):80-83.
Wooley, K. L., C. J. Hawker, J. M. Pochan and J. M. J. Frechet (1993). "Physical properties of dendritic macromolecules:a study of glass transition temperature." Macromolecules 26(7): 1514-1519.
Yang, K., Y. Y. Cheng, X. Y. Feng, J. H. Zhang, Q. L. Wu and T. W. Xu (2010). "Insights into the interactions between dendrimers and multiple surfactants:5. formation of miscellaneous mixed micelles revealed by a combination of 1H NMR, diffusion, and NOE analysis." Journal of Physical Chemistry B 114(21):7265-7273.
Yang, K., L. A. Weng, Y. Y. Cheng, H. F. Zhang, J. H. Zhang, Q. L. Wu and T. W. Xu (2011). "Host-guest chemistry of dendrimer-drug complexes.6. fully acetylated dendrimers as biocompatible drug vehicles using dexamethasone 21-phosphate as a model drug." Journal of Physical Chemistry B 115(10):2185-2195.
Yaseen, M. A., J. Yu, M. S. Wong and B. Anvari (2007). "Stability assessment of indocyanine green within dextran-coated mesocapsules by absorbance spectroscopy." Journal of Biomedical Optics 12(6).
Zhao, L., Y. Cheng, J. Hu, Q. Wu and T. Xu (2009). "Host-guest chemistry of dendrimer-drug complexes.3. competitive binding of multiple drugs by a single dendrimer for combination therapy." The Journal of Physical Chemistry B 113(43):14172-14179.
Zhao, L. B., Q. L. Wu, Y. Y. Cheng, J. H. Zhang, J. H. Wu and T. W. Xu (2010). "High-throughput screening of dendrimer-binding drugs." Journal of the American Chemical Society 132(38):13182-13184.
Zheng, X. H., D. Xing, F. F. Zhou, B. Y. Wu and W. R. Chen (2011). "Indocyanine green-containing nanostructure as near infrared dual-functional targeting probes for optical imaging and photothermal therapy." Molecular Pharmaceutics 8(2):447-456.
谭惠民,罗运军(2001).树枝形聚合物：1-7.