Advertisement

From Polymers to Nanomedicines: New Materials for Future Vaccines

  • Philipp Heller
  • David Huesmann
  • Martin Scherer
  • Matthias Barz

Abstract

Nanomedicine is the medical application of nanotechnology and therefore covers various kinds of nanoparticles. In this chapter, we would like to provide a brief introduction and overview of nanoparticles for the modulation of the immune system. In general, these nano-sized objects can be inorganic colloids, organic colloids (synthesized by emulsion polymerization or mini-/nanoemulsion techniques), polymeric aggregates (micelles or polymersomes), core cross-linked aggregates (nanohydrogels, crosslinked micelles, or polyplexes), multifunctional polymer coils, dendritic polymers or perfect dendrimers. A special focus is set on polymeric materials, because the chemical composition of the particle corona will shape particle properties by providing steric stabilization, avoiding protein adsorption and particle aggregation in vivo. Besides synthesis of new materials, particle characterization is equally important and might be the key to a more detailed understanding of the behavior of nano-sized systems. In addition, we would like to highlight approaches towards nanoparticle-based immunotherapies.

Keywords

Block Copolymer West Nile Virus Atom Transfer Radical Polymerization Atom Transfer Radical Polymerization Lower Critical Solution Temperature 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Duffus, J.H., Nordberg, M., Templeton, D.M.: Glossary of terms used in toxicology, 2nd edition (IUPAC Recommendations 2007). Pure Appl. Chem. 79, 1153–1344 (2007)Google Scholar
  2. 2.
    Duncan, R., Gaspar, R.: Nanomedicine(s) under the microscope. Mol. Pharm. 8, 2101–2141 (2011)PubMedGoogle Scholar
  3. 3.
    Johnston, A.P.R., Such, G.K., Ng, S.L., Caruso, F.: Challenges facing colloidal delivery systems: from synthesis to the clinic. Curr. Opin. Colloid In.. 16, 171–181 (2011)Google Scholar
  4. 4.
    Torchilin, V.P.: Micellar nanocarriers: pharmaceutical perspectives. Pharm. Res. 24, 1–16 (2007)PubMedGoogle Scholar
  5. 5.
    Lasic, D.D., Martin, F.J.: Stealth Liposomes. CRC Press, Boca Raton (1995)Google Scholar
  6. 6.
    Hobbs, S.K., et al.: Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc. Natl. Acad. Sci. U. S. A. 95, 4607–4612 (1998)PubMedGoogle Scholar
  7. 7.
    Torchilin, V.P.: Targeted polymeric micelles for delivery of poorly soluble drugs. Cell. Mol. Life Sci. 61, 2549–2559 (2004)PubMedGoogle Scholar
  8. 8.
    Nagasaki, Y., Yasugi, K., Yamamoto, Y., Harada, A., Kataoka, K.: Sugar-installed block copolymer micelles: their preparation and specific interaction with lectin molecules. Biomacromolecules 2, 1067–1070 (2001)PubMedGoogle Scholar
  9. 9.
    Ogris, M., Brunner, S., Schuller, S., Kircheis, R., Wagner, E.: PEGylated DNA/transferrin-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther. 6, 595–605 (1999)PubMedGoogle Scholar
  10. 10.
    Leamon, C.P., Weigl, D., Hendren, R.W.: Folate copolymer-mediated transfection of cultured cells. Bioconjug. Chem. 10, 947–957 (1999)PubMedGoogle Scholar
  11. 11.
    Hopewell, J.W., Duncan, R., Wilding, D., Chakrabarti, K.: Preclinical evaluation of the cardiotoxicity of PK2: a novel HPMA copolymer–doxorubicin–galactosamine conjugate antitumour agent. Hum. Exp. Toxicol. 20, 461–470 (2001)Google Scholar
  12. 12.
    Ahmed, F., et al.: Shrinkage of a rapidly growing tumor by drug-loaded polymersomes: pH-triggered release through copolymer degradation. Mol. Pharm. 3, 340–350 (2006)PubMedGoogle Scholar
  13. 13.
    Saito, G., Swanson, J.A., Lee, K.-D.: Drug delivery strategy utilizing conjugation via reversible disulfide linkages: role and site of cellular reducing activities. Adv. Drug Deliv. Rev. 55, 199–215 (2003)PubMedGoogle Scholar
  14. 14.
    Thornton, P.D., Mart, R.J., Webb, S.J., Ulijn, R.V.: Enzyme-responsive hydrogel particles for the controlled release of proteins: designing peptide actuators to match payload. Soft Matter 4, 821–827 (2008)Google Scholar
  15. 15.
    Ishida, O., Maruyama, K., Yanagie, H., Iwatsuru, M., Eriguchi, M.: Targeting chemotherapy to solid tumors with long circulating thermosensitive liposomes and local hyperthermia. Jpn. J. Cancer Res. 91, 118–126 (2000)PubMedGoogle Scholar
  16. 16.
    Edelman, E.R., Kost, J., Bobeck, H., Langer, R.: Regulation of drug release from polymer matrices by oscillating magnetic fields. J. Biomed. Mater. Res. 19, 67–83 (1985)PubMedGoogle Scholar
  17. 17.
    Langer, R.: New methods of drug delivery. Science 249, 1527–1533 (1990)PubMedGoogle Scholar
  18. 18.
    Uhrich, K.E., Cannizzaro, S.M., Langer, R.S., Shakesheff, K.M.: Polymeric systems for controlled drug release. Chem. Rev. 99, 3181–3198 (1999)PubMedGoogle Scholar
  19. 19.
    Little, S.R.: Reorienting our view of particle-based adjuvants for subunit vaccines. Proc. Natl. Acad. Sci. 109, 999–1000 (2012)PubMedGoogle Scholar
  20. 20.
    Moon, J.J., et al.: Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells and promote germinal center induction. Proc. Natl. Acad. Sci. U. S. A. 109, 1080–1085 (2012)PubMedGoogle Scholar
  21. 21.
    Prokop, A., Davidson, J.M.: Nanovehicular intracellular delivery systems. J. Pharm. Sci. 97, 3518–3590 (2008)PubMedGoogle Scholar
  22. 22.
    Gref, R., et al.: Biodegradable long-circulating polymeric nanospheres. Science 263, 1600–1603 (1994)PubMedGoogle Scholar
  23. 23.
    Owens, D.E., Peppas, N.A.: Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm. 307, 93–102 (2006)PubMedGoogle Scholar
  24. 24.
    Frank, M., Fries, L.: The role of complement in inflammation and phagocytosis. Immunol. Today 12, 322–326 (1991)PubMedGoogle Scholar
  25. 25.
    Johnson, R.J.: The complement system. In: Ratner, B.D., Hoffman, A.S., Schoen, F.J., Lemons, J.E. (eds.) Biomaterials Science: An Introduction to Materials in Medicine, pp. 318–328. Elsevier/Academic, Amsterdam (2004)Google Scholar
  26. 26.
    Ostuni, E., Chapman, R.G., Holmlin, R.E., Takayama, S., Whitesides, G.M.: A survey of structure–property relationships of surfaces that resist the adsorption of protein. Langmuir 17, 5605–5620 (2001)Google Scholar
  27. 27.
    Scheibe, P., Barz, M., Hemmelmann, M., Zentel, R.: Langmuir-Blodgett films of biocompatible poly (HPMA)-block-poly(lauryl methacrylate) and poly(HPMA)-random-poly(lauryl methacrylate): influence of polymer structure on membrane formation and stability. Langmuir 26, 5661–5669 (2010)PubMedGoogle Scholar
  28. 28.
    Kelsch, A., et al.: HPMA copolymers as surfactants in the preparation of biocompatible nanoparticles for biomedical application. Biomacromolecules 13, 4179–4187 (2012)PubMedGoogle Scholar
  29. 29.
    Riess, G.: Micellization of block copolymers. Prog. Polym. Sci. 28, 1107–1170 (2003)Google Scholar
  30. 30.
    O’Reilly, R.K., Hawker, C.J., Wooley, K.L.: Cross-linked block copolymer micelles: functional nanostructures of great potential and versatility. Chem. Soc. Rev. 35, 1068–1083 (2006)PubMedGoogle Scholar
  31. 31.
    Kabanov, A.V., Vinogradov, S.V.: Nanogels as pharmaceutical carriers: finite networks of infinite capabilities. Angew. Chem. Int. Ed. Engl. 48, 5418–5429 (2009)PubMedGoogle Scholar
  32. 32.
    Christie, R.J., Nishiyama, N., Kataoka, K.: Delivering the code: polyplex carriers for deoxyribonucleic acid and ribonucleic acid interference therapies. Endocrinology 151, 466–473 (2010)PubMedGoogle Scholar
  33. 33.
    Miyata, K., Nishiyama, N., Kataoka, K.: Rational design of smart supramolecular assemblies for gene delivery: chemical challenges in the creation of artificial viruses. Chem. Soc. Rev. 41, 2562–2574 (2012)PubMedGoogle Scholar
  34. 34.
    Kataoka, K., Harada, A., Nagasaki, Y.: Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv. Drug Deliv. Rev. 47, 113–131 (2001)PubMedGoogle Scholar
  35. 35.
    Torchilin, V.P.: Structure and design of polymeric surfactant-based drug delivery systems. J. Control. Release 73, 137–172 (2001)PubMedGoogle Scholar
  36. 36.
    Gaucher, G., et al.: Block copolymer micelles: preparation, characterization and application in drug delivery. J. Control. Release 109, 169–188 (2005)PubMedGoogle Scholar
  37. 37.
    Nuhn, L., et al.: Cationic nanohydrogel particles as potential siRNA carriers for cellular delivery. ACS Nano 6, 2198–2214 (2012)PubMedGoogle Scholar
  38. 38.
    Fleige, E., Quadir, M.A., Haag, R.: Stimuli-responsive polymeric nanocarriers for the controlled transport of active compounds: concepts and applications. Adv. Drug Deliv. Rev. 64, 866–884 (2012)PubMedGoogle Scholar
  39. 39.
    Jesorka, A., Orwar, O.: Liposomes: technologies and analytical applications. Annu. Rev. Anal. Chem. 1, 801–832 (2008)Google Scholar
  40. 40.
    Torchilin, V.P.: Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov. 4, 145–160 (2005)PubMedGoogle Scholar
  41. 41.
    Szoka, F.C.: Comparative properties and methods of preparation of lipid vesicles (liposomes). Ann. Rev. Biophys. Bioeng. 9, 467–508 (1980)Google Scholar
  42. 42.
    Lasic, D.D.: Sterically stabilized vesicles. Angew. Chem. Int. Ed. Engl. 33, 1685–1698 (1994)Google Scholar
  43. 43.
    Allen, T.M., Cullis, P.R.: Drug delivery systems: entering the mainstream. Science 303, 1818–1822 (2004)PubMedGoogle Scholar
  44. 44.
    White, K.L., Rades, T., Furneaux, R.H., Tyler, P.C., Hook, S.: Mannosylated liposomes as antigen delivery vehicles for targeting to dendritic cells. J. Pharm. Pharmacol. 58, 729–737 (2006)PubMedGoogle Scholar
  45. 45.
    Drummond, D.C., Meyer, O., Hong, K., Kirpotin, D.B., Papahadjopoulos, D.: Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol. Rev. 51, 691–744 (1999)PubMedGoogle Scholar
  46. 46.
    Krishnamachari, Y., Geary, S.M., Lemke, C.D., Salem, A.K.: Nanoparticle delivery systems in cancer vaccines. Pharm. Res. 28, 215–236 (2011)PubMedGoogle Scholar
  47. 47.
    Gluck, R.: Immunopotentiating reconstituted influenza virosomes (IRIVs) and other adjuvants for improved presentation of small antigens. Vaccine 10, 915–919 (1992)PubMedGoogle Scholar
  48. 48.
    Moser, C., et al.: Influenza virosomes as a combined vaccine carrier and adjuvant system for prophylactic and therapeutic immunizations. Expert Rev. Vaccines 6, 711–721 (2007)PubMedGoogle Scholar
  49. 49.
    Kayser, O., Olbrich, C., Croft, S.L., Kiderlein, A.F.: Formulation and biopharmaceutical issues in the development of drug delivery systems for antiparasitic drugs. Parasitol. Res. 90, S63–S70 (2003)PubMedGoogle Scholar
  50. 50.
    Discher, D.E., Ahmed, F.: Polymersomes. Annu. Rev. Biomed. Eng. 8, 323–341 (2006)PubMedGoogle Scholar
  51. 51.
    Levine, D.H., et al.: Polymersomes: a new multi-functional tool for cancer diagnosis and therapy. Methods 46, 25–32 (2008)PubMedGoogle Scholar
  52. 52.
    Osterhaus, A., Rimmelzwaan, G.F.: Induction of virus-specific immunity by ISCOMs. Dev. Biol. Stand. 92, 49–58 (1998)PubMedGoogle Scholar
  53. 53.
    Saupe, A., McBurney, W., Rades, T., Hook, S.: Immunostimulatory colloidal delivery systems for cancer vaccines. Expert Opin. Drug Deliv. 3, 345–354 (2006)PubMedGoogle Scholar
  54. 54.
    Westesen, K., Siekmann, B.: Biodegradable colloidal drug carrier systems based on solid lipids. In: Benita, S. (ed.) Microencapsulation, pp. 213–258. Marcel Dekker, New York (1996)Google Scholar
  55. 55.
    Bunjes, H.: Lipid nanoparticles for the delivery of poorly water-soluble drugs. J. Pharm. Pharmacol. 62, 1637–1645 (2010)PubMedGoogle Scholar
  56. 56.
    Petersen, S., Steiniger, F., Fischer, D., Fahr, A., Bunjes, H.: The physical state of lipid nanoparticles affects their in vitro cell viability. Eur. J. Pharm. Biopharm. 79, 150–161 (2011)PubMedGoogle Scholar
  57. 57.
    Shi, R., et al.: Enhanced immune response to gastric cancer specific antigen peptide by coencapsulation with CpG oligodeoxynucleotides in nanoemulsion. Cancer Biol. Ther. 4, 218–242 (2005)PubMedGoogle Scholar
  58. 58.
    Gupta, S., Moulik, S.P.: Biocompatible microemulsions and their prospective uses in drug delivery. J. Pharm. Sci. 97, 22–45 (2008)PubMedGoogle Scholar
  59. 59.
    Fanun, M.: Microemulsions as delivery systems. Curr. Opin. Colloid In. 17, 306–313 (2012)Google Scholar
  60. 60.
    Sailaja, A.K., Amareshwar, P., Chakravarty, P.: Chitosan nanoparticles as a drug delivery system. Res. J. Pharm. Biol. Chem. Sci. 1, 474–484 (2010)Google Scholar
  61. 61.
    Lohse, S.E., Murphy, C.J.: Applications of colloidal inorganic nanoparticles: from medicine to energy. J. Am. Chem. Soc. 134, 15607–15620 (2012)PubMedGoogle Scholar
  62. 62.
    Landfester, K.: Synthesis of colloidal particles in miniemulsions. Annu. Rev. Mater. Res. 36, 231–279 (2006)Google Scholar
  63. 63.
    Klinger, D., Landfester, K.: Stimuli-responsive microgels for the loading and release of functional compounds: Fundamental concepts and applications. Polymer 53, 5209–5231 (2012)Google Scholar
  64. 64.
    Ugelstad, J., Mork, P.C., Kaggerud, K.H., Ellingsen, T., Berge, A.: Swelling of oligomer-polymer particles: new method of preparation of emulsions and polymer dispersions. Adv. Colloid Interface Sci. 13, 101–140 (1980)Google Scholar
  65. 65.
    Chern, C.S., Chen, T.J., Liou, Y.C.: Miniemulsion polymerization of styrene in the presence of a water-insoluble blue dye. Polymer 37, 3767–3777 (1998)Google Scholar
  66. 66.
    Reimers, J.L., Schork, F.J.: Lauroyl peroxide as a cosurfactant in miniemulsion polymerization. Ind. Eng. Chem. Res. 36, 1085–1087 (1997)Google Scholar
  67. 67.
    Landfester, K.: Recent developments in miniemulsions – formation and stability mechanisms. Macromol. Symp. 150, 171–178 (2000)Google Scholar
  68. 68.
    Tamber, H., Johansen, P., Merkle, H.P., Gander, B.: Formulation aspects of biodegradable polymeric microspheres for antigen delivery. Adv. Drug Deliv. Rev. 57, 357–376 (2005)PubMedGoogle Scholar
  69. 69.
    Mok, H., Park, T.G.: Direct plasmid DNA encapsulation within PLGA nanospheres by single oil-in-water emulsion method. Eur. J. Pharm. Biopharm. 68, 105–111 (2008)PubMedGoogle Scholar
  70. 70.
    Meyer, J.D., Manning, M.C.: Hydrophobic ion pairing: altering the solubility properties of biomolecules. Pharm. Res. 15, 188–193 (1998)PubMedGoogle Scholar
  71. 71.
    Kazzaz, J., Neidleman, J., Singh, M., Ott, G., O’Hagan, D.T.: Novel anionic microparticles are a potent adjuvant for the induction of cytotoxic T lymphocytes against recombinant p55 gag from HIV-1. J. Control. Release 67, 347–356 (2000)PubMedGoogle Scholar
  72. 72.
    Schwendeman, S.P.: Recent advances in the stabilization of proteins encapsulated in injectable PLGA delivery systems. Crit. Rev. Ther. Drug Carr. Syst. 19, 73–98 (2002)Google Scholar
  73. 73.
    Barz, M., et al.: Synthesis, characterization and preliminary biological evaluation of P(HPMA)-b-P(LLA) copolymers: a new type of functional biocompatible block copolymer. Macromol. Rapid Comm. 31, 1492–1500 (2010)Google Scholar
  74. 74.
    Barz, M., et al.: P(HPMA)-block-P(LA) copolymers in paclitaxel formulations: polylactide stereochemistry controls micellization, cellular uptake kinetics, intracellular localization and drug efficiency. J. Control. Release 163, 63–74 (2012)PubMedGoogle Scholar
  75. 75.
    Aspinall, G.O.: The Polysaccharides 35. Academic, New York (1982)Google Scholar
  76. 76.
    Leonard, M., et al.: Preparation of polysaccharide-covered polymeric nanoparticles by several processes involving amphiphilic polysaccharides. ACS Symp. Ser. 996, 322–340 (2008)Google Scholar
  77. 77.
    Artursson, P., Lindmark, T., Davis, S., Illum, L.: Effect of chitosan on the permeability of monolayers of intestinal epithelial-cells (Caco-2). Pharm. Res. 11, 1358–1361 (1994)PubMedGoogle Scholar
  78. 78.
    Domard, A., Gey, C., Rinaudo, M., Terrassin, C., et al.: C-13 and H-1-NMR spectroscopy of chitosan and Ntrimethyl chloride derivates. Int. J. Biol. Macromol. 9, 233–237 (1987)Google Scholar
  79. 79.
    Sundar, S., Kundu, J., Kundu, S.C.: Biopolymeric nanoparticles. Sci. Technol. Adv. Mater. (11) (2010)Google Scholar
  80. 80.
    Schultze, V., et al.: Safety of MF59(TM) adjuvant. Vaccine 26, 3209–3222 (2008)PubMedGoogle Scholar
  81. 81.
    Makidon, P.E., et al.: Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine. PLoS One 3, e2954 (2008)PubMedGoogle Scholar
  82. 82.
    Bielinska, A.U., et al.: Nasal immunization with a recombinant HIV gp120 and nanoemulsion adjuvant produces Th1 polarized responses and neutralizing antibodies to primary HIV type 1 isolates. AIDS Res. Hum. Retrov. 24, 271–281 (2008)Google Scholar
  83. 83.
    Ge, W., et al.: The antitumor immune responses induced by nanoemulsion encapsulated MAGE1-HSP70/SEA complex protein vaccine following different administration routes. Oncol. Rep. 22, 915–920 (2009)PubMedGoogle Scholar
  84. 84.
    Rolland, J.P., et al.: Direct fabrication and harvesting of monodisperse. Shape-specific nanobiomaterials. J. Am. Chem. Soc. 127, 10096–10100 (2005)PubMedGoogle Scholar
  85. 85.
    Gratton, S.E., et al.: Nanofabricated particles for engineered drug therapies: a preliminary biodistribution study of PRINT nanoparticles. J. Control. Release 121, 10–18 (2007)PubMedGoogle Scholar
  86. 86.
    Dunn, S.S., et al.: Reductively responsive siRNA-conjugated hydrogel nanoparticles for gene silencing. J. Am. Chem. Soc. 134, 7423–7430 (2012)PubMedGoogle Scholar
  87. 87.
    Laurent, S., et al.: Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem. Rev. 108, 2064–2110 (2008)PubMedGoogle Scholar
  88. 88.
    Dahl, J.A., Maddux, B.L.S., Hutchison, J.E.: Toward greener nanosynthesis. Chem. Rev. 107, 2228–2269 (2007)PubMedGoogle Scholar
  89. 89.
    Caragheorgheopol, A., Chechik, V.: Mechanistic aspects of ligand exchange in Au nanoparticles. Phys. Chem. Chem. Phys. 10, 5029–5041 (2008)PubMedGoogle Scholar
  90. 90.
    Bernardi, R.J., Lowery, A.R., Thompson, P.A., Blaney, S.M., West, J.L.: Immunonanoshells for targeted photothermal ablation in medulloblastoma and glioma: an in vitro evaluation using human cell lines. J. Neurooncol 86, 165–172 (2008)PubMedGoogle Scholar
  91. 91.
    Cruz, L.J., et al.: Targeting nanosystems to human DCs via Fc receptor as an effective strategy to deliver antigen for immunotherapy. Mol. Pharm. 8, 104–116 (2011)PubMedGoogle Scholar
  92. 92.
    Ito, A., Honda, H., Kobayashi, T.: Cancer immunotherapy based on intracellular hyperthermia using magnetite nanoparticles: a novel concept of “heat-controlled necrosis” with heat shock protein expression. Cancer Immunol. Immunother. 55, 320–328 (2006)PubMedGoogle Scholar
  93. 93.
    Masoudi, A., Madaah Hosseini, H.R., Shokrgozar, M.A., Ahmadi, R., Oghabian, M.A.: The effect of poly(ethylene glycol) coating on colloidal stability of superparamagnetic iron oxide nanoparticles as potential MRI contrast agent. Int. J. Pharm. 433, 129–141 (2012)PubMedGoogle Scholar
  94. 94.
    Webster, R. et al.: PEG and PEG conjugates toxicity: towards an understanding of the toxicity of PEG and its relevance to PEGylated biologicals. In: PEGylated Protein Drugs: Basic Science and Clinical Applications. Birkhäuser Verlag, Basel (2009) pp. 127–146Google Scholar
  95. 95.
    Bendele, A., Seely, J., Richey, C., Sennello, G., Shopp, G.: Short communication: renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated proteins. Toxicol. Sci. 42, 152–157 (1998)PubMedGoogle Scholar
  96. 96.
    Young, M.A., Malavalli, A., Winslow, N., Vandegriff, K.D., Winslow, R.M.: Toxicity and hemodynamic effects after single dose administration of MalPEG-hemoglobin (MP4) in rhesus monkeys. Transl. Res. 149, 333–342 (2007)PubMedGoogle Scholar
  97. 97.
    Chapman, R.G., et al.: Surveying for surfaces that resist the adsorption of proteins. J. Am. Chem. Soc. 122, 8303–8304 (2000)Google Scholar
  98. 98.
    Zhou, M., et al.: High throughput discovery of new fouling-resistant surfaces. J. Mater. Chem. 21, 693 (2011)Google Scholar
  99. 99.
    Fasting, C., et al.: Multivalency as a chemical organization and action principle. Angew. Chem. Int. Ed. Engl. 51, 10472–10498 (2012)PubMedGoogle Scholar
  100. 100.
    Niederhafner, P., Reinis, M., Sebestík, J., Jezek, J.: Glycopeptide dendrimers, part III: a review. Use of glycopeptide dendrimers in immunotherapy and diagnosis of cancer and viral diseases. J. Pept. Sci. 14, 556–587 (2008)PubMedGoogle Scholar
  101. 101.
    Günay, K.A., Theato, P., Klok, H.A.: Standing on the shoulders of Hermann Staudinger: post-polymerization modification from past to present. J. Polym. Sci. A1 51, 1–28 (2013)Google Scholar
  102. 102.
    Grandjean, C., Boutonnier, A., Guerreiro, C., Fournier, J.-M., Mulard, L.A.: On the preparation of carbohydrate-protein conjugates using the traceless Staudinger ligation. J. Org. Chem. 70, 7123–7132 (2005)PubMedGoogle Scholar
  103. 103.
    Xu, P., et al.: Simple, direct conjugation of bacterial O-SP-core antigens to proteins: development of cholera conjugate vaccines. Bioconjugate Chem. 22, 2179–2185 (2011)Google Scholar
  104. 104.
    Scaramuzza, S., et al.: A new site-specific monoPEGylated filgrastim derivative prepared by enzymatic conjugation: production and physicochemical characterization. J. Control. Release 164, 355–363 (2012)PubMedGoogle Scholar
  105. 105.
    Jung, B., Theato, P.: Chemical strategies for the synthesis of protein – polymer conjugates. Bio-synth. Polym. Conjugates 253, 37–70 (2013)Google Scholar
  106. 106.
    Moad, G., Rizzardo, E., Thang, S.H.: Living radical polymerization by the RAFT process. Aust. J. Chem. 58, 379 (2005)Google Scholar
  107. 107.
    Moad, G., Rizzardo, E., Thang, S.H.: Radical addition–fragmentation chemistry in polymer synthesis. Polymer 49, 1079–1131 (2008)Google Scholar
  108. 108.
    Braunecker, W.A., Matyjaszewski, K.: Controlled/living radical polymerization: features, developments, and perspectives. Prog. Polym. Sci. 32, 93–146 (2007)Google Scholar
  109. 109.
    Matyjaszewski, K., Xia, J.: Atom transfer radical polymerization. Chem. Rev. 101, 2921–2990 (2001)PubMedGoogle Scholar
  110. 110.
    York, A.W., Kirkland, S.E., McCormick, C.L.: Advances in the synthesis of amphiphilic block copolymers via RAFT polymerization: stimuli-responsive drug and gene delivery. Adv. Drug Deliv. Rev. 60, 1018–1036 (2008)PubMedGoogle Scholar
  111. 111.
    Gao, H., Matyjaszewski, K.: Synthesis of functional polymers with controlled architecture by CRP of monomers in the presence of cross-linkers: from stars to gels. Prog. Polym. Sci. 34, 317–350 (2009)Google Scholar
  112. 112.
    Marsden, H.R., Kros, A.: Polymer-peptide block copolymers – an overview and assessment of synthesis methods. Macromol. Biosci. 9, 939–951 (2009)Google Scholar
  113. 113.
    Tizzotti, M., Charlot, A., Fleury, E., Stenzel, M., Bernard, J.: Modification of polysaccharides through controlled/living radical polymerization grafting-towards the generation of high performance hybrids. Macromol. Rapid Comm. 31, 1751–1772 (2010)Google Scholar
  114. 114.
    Lutz, J.F.: Polymerization of oligo(ethylene glycol) (meth)acrylates: toward new generations of smart biocompatible materials. J. Polym. Sci. A1 46, 3459–3470 (2008)Google Scholar
  115. 115.
    Lutz, J.-F., Akdemir, O., Hoth, A.: Point by point comparison of two thermosensitive polymers exhibiting a similar LCST: is the age of poly(NIPAM) over? J. Am. Chem. Soc. 128, 13046–13047 (2006)PubMedGoogle Scholar
  116. 116.
    Tao, L., Mantovani, G., Lecolley, F., Haddleton, D.M.: Alpha-aldehyde terminally functional methacrylic polymers from living radical polymerization: application in protein conjugation “pegylation”. J. Am. Chem. Soc. 126, 13220–13221 (2004)PubMedGoogle Scholar
  117. 117.
    Lutz, J.-F., Hoth, A.: Preparation of Ideal PEG analogues with a tunable thermosensitivity by controlled radical copolymerization of 2-(2-Methoxyethoxy)ethyl methacrylate and oligo(ethylene glycol) methacrylate. Macromolecules 39, 893–896 (2006)Google Scholar
  118. 118.
    Ryan, S.M., et al.: Conjugation of salmon calcitonin to a combed-shaped end functionalized poly(poly(ethylene glycol) methyl ether methacrylate) yields a bioactive stable conjugate. J. Control. Release 135, 51–59 (2009)PubMedGoogle Scholar
  119. 119.
    Lutz, J.-F., Andrieu, J., Üzgün, S., Rudolph, C., Agarwal, S.: Biocompatible, thermoresponsive, and biodegradable: simple preparation of “all-in-one” biorelevant polymers. Macromolecules 40, 8540–8543 (2007)Google Scholar
  120. 120.
    Ishihara, K., Ziats, N.P., Tierney, B.P., Nakabayashi, N., Anderson, J.M.: Protein adsorption from human plasma is reduced on phospholipid polymers. J. Biomed. Mater. Res. A 25, 1397–1407 (1991)Google Scholar
  121. 121.
    Salvage, J.P., et al.: Novel biocompatible phosphorylcholine-based self-assembled nanoparticles for drug delivery. J. Control. Release 104, 259–270 (2005)PubMedGoogle Scholar
  122. 122.
    Murdoch, C., et al.: Internalization and biodistribution of polymersomes into oral squamous cell carcinoma cells in vitro and in vivo. Nanomedicine 5, 1025–1036 (2010)PubMedGoogle Scholar
  123. 123.
    Lomas, H., et al.: Non-cytotoxic polymer vesicles for rapid and efficient intracellular delivery. Faraday Discuss. 139, 143–159 (2008)PubMedGoogle Scholar
  124. 124.
    Lewis, A., Tang, Y., Brocchini, S., Choi, J.-W., Godwin, A.: Poly(2-methacryloyloxyethyl phosphorylcholine) for protein conjugation. Bioconjugate Chem. 19, 2144–2155 (2008)Google Scholar
  125. 125.
    Kopecek, J., Kopecková, P.: HPMA copolymers: origins, early developments, present, and future. Adv. Drug Deliv. Rev. 62, 122–149 (2010)PubMedGoogle Scholar
  126. 126.
    Barz, M., et al.: From defined reactive diblock copolymers to functional HPMA-based self-assembled nanoaggregates. Biomacromolecules 9, 3114–3118 (2008)PubMedGoogle Scholar
  127. 127.
    Barz, M., Canal, F., Koynov, K., Zentel, R., Vicent, M.J.: Synthesis and in vitro evaluation of defined HPMA folate conjugates: influence of aggregation on folate receptor (FR) mediated cellular uptake. Biomacromolecules 11, 2274–2282 (2010)PubMedGoogle Scholar
  128. 128.
    Leuchs, H.: Über die Glycin-carbonsäure. Ber. Dtsch. Chem. Ges. 39, 857–861 (1906)Google Scholar
  129. 129.
    Kricheldorf, H.R.: α-Amino acid-N-Carboxy-Anhydrides and Related Heterocycles: Syntheses, Properties, Peptide Synthesis, Polymerization. Springer, Berlin/Heidelberg/New York (1987)Google Scholar
  130. 130.
    Kricheldorf, H.R.: Polypeptides and 100 years of chemistry of alpha-amino acid N-carboxyanhydrides. Angew. Chem. Int. Ed. Engl. 45, 5752–5784 (2006)PubMedGoogle Scholar
  131. 131.
    Hadjichristidis, N., Iatrou, H., Pitsikalis, M., Sakellariou, G.: Synthesis of well-defined polypeptide-based materials via the ring-opening polymerization of alpha-amino acid N-carboxyanhydrides. Chem. Rev. 109, 5528–5578 (2009)PubMedGoogle Scholar
  132. 132.
    Bogdanov, A.A., et al.: A new macromolecule as a contrast agent for MR angiography: preparation, properties, and animal studies. Radiology 187, 701–706 (1993)PubMedGoogle Scholar
  133. 133.
    Singer, J.W., et al.: Paclitaxel poliglumex (XYOTAX; CT-2103): an intracellularly targeted taxane. Anti-cancer Drug. 16, 243–254 (2005)Google Scholar
  134. 134.
    Harada, A., Kataoka, K.: Formation of polyion complex micelles in an aqueous milieu from a pair of oppositely-charged block copolymers with poly(ethylene glycol) segments. Macromolecules 28, 5294–5299 (1995)Google Scholar
  135. 135.
    Carlsen, A., Lecommandoux, S.: Self-assembly of polypeptide-based block copolymer amphiphiles. Curr. Opin. Colloid In. 14, 329–339 (2009)Google Scholar
  136. 136.
    Deng, J., et al.: Self-assembled cationic micelles based on PEG-PLL-PLLeu hybrid polypeptides as highly effective gene vectors. Biomacromolecules 13, 3795–3804 (2012)PubMedGoogle Scholar
  137. 137.
    Bellomo, E.G., Wyrsta, M.D., Pakstis, L., Pochan, D.J., Deming, T.J.: Stimuli-responsive polypeptide vesicles by conformation-specific assembly. Nat. Mater. 3, 244–248 (2004)PubMedGoogle Scholar
  138. 138.
    Holowka, E.P., Sun, V.Z., Kamei, D.T., Deming, T.J.: Polyarginine segments in block copolypeptides drive both vesicular assembly and intracellular delivery. Nat. Mater. 6, 52–57 (2007)PubMedGoogle Scholar
  139. 139.
    Kanzaki, T., Horikawa, Y., Makino, A., Sugiyama, J., Kimura, S.: Nanotube and three-way nanotube formation with nonionic amphiphilic block peptides. Macromol. Biosci. 8, 1026–1033 (2008)PubMedGoogle Scholar
  140. 140.
    Nowak, A.P., et al.: Rapidly recovering hydrogel scaffolds from self-assembling diblock copolypeptide amphiphiles. Nature 417, 424–428 (2002)PubMedGoogle Scholar
  141. 141.
    Takae, S., et al.: PEG-detachable polyplex micelles based on disulfide-linked block catiomers as bioresponsive nonviral gene vectors. J. Am. Chem. Soc. 130, 6001–6009 (2008)PubMedGoogle Scholar
  142. 142.
    Uchida, H., et al.: Odd-even effect of repeating aminoethylene units in the side chain of N-substituted polyaspartamides on gene transfection profiles. J. Am. Chem. Soc. 133, 15524–15532 (2011)PubMedGoogle Scholar
  143. 143.
    Sanjoh, M., et al.: Dual environment-responsive polyplex carriers for enhanced intracellular delivery of plasmid DNA. Biomacromolecules 13, 3641–3649 (2012)PubMedGoogle Scholar
  144. 144.
    Naito, M., et al.: A phenylboronate-functionalized polyion complex micelle for ATP-triggered release of siRNA. Angew. Chem. Int. Ed. Engl. 124, 10909–10913 (2012)Google Scholar
  145. 145.
    Hamaguchi, T., et al.: NK105, a paclitaxel-incorporating micellar nanoparticle formulation, can extend in vivo antitumour activity and reduce the neurotoxicity of paclitaxel. Brit. J. Cancer 92, 1240–1246 (2005)PubMedGoogle Scholar
  146. 146.
    Weissleder, R., Tung, C.H., Mahmood, U., Bogdanov, A.: In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat. Biotechnol. 17, 375–378 (1999)PubMedGoogle Scholar
  147. 147.
    Arnon, R.: The development of Cop 1 (Copaxone), an innovative drug for the treatment of multiple sclerosis: personal reflections. Immunol. Lett. 50, 1–15 (1996)PubMedGoogle Scholar
  148. 148.
    Shaffer, S.A., et al.: In vitro and in vivo metabolism of paclitaxel poliglumex: identification of metabolites and active proteases. Cancer Chemother. Pharmacol. 59, 537–548 (2007)PubMedGoogle Scholar
  149. 149.
    Hanson, J.A., et al.: Nanoscale double emulsions stabilized by single-component block copolypeptides. Nature 455, 85–88 (2008)PubMedGoogle Scholar
  150. 150.
    Matsumura, Y.: Poly (amino acid) micelle nanocarriers in preclinical and clinical studies. Adv. Drug Deliv. Rev. 60, 899–914 (2008)PubMedGoogle Scholar
  151. 151.
  152. 152.
    Li, C., Wallace, S.: Polymer-drug conjugates: recent development in clinical oncology. Adv. Drug Deliv. Rev. 60, 886–898 (2008)PubMedGoogle Scholar
  153. 153.
    Wilms, D., Stiriba, S.-E., Frey, H.: Hyperbranched polyglycerols: from the controlled synthesis of biocompatible polyether polyols to multipurpose applications. Acc. Chem. Res. 43, 129–141 (2010)PubMedGoogle Scholar
  154. 154.
    Quadir, M.A., Haag, R.: Biofunctional nanosystems based on dendritic polymers. J. Control. Release 161, 484–495 (2012)PubMedGoogle Scholar
  155. 155.
    Khandare, J., Calderón, M., Dagia, N.M., Haag, R.: Multifunctional dendritic polymers in nanomedicine: opportunities and challenges. Chem. Soc. Rev. 41, 2824–2848 (2012)PubMedGoogle Scholar
  156. 156.
    Mourey, T.H., et al.: Unique behavior of dendritic macromolecules: intrinsic viscosity of polyether dendrimers. Macromolecules 25, 2401–2406 (1992)Google Scholar
  157. 157.
    Wyszogrodzka, M., Haag, R.: Study of single protein adsorption onto monoamino oligoglycerol derivatives: a structure-activity relationship. Langmuir 25, 5703–5712 (2009)PubMedGoogle Scholar
  158. 158.
    Wyszogrodzka, M., et al.: New approaches towards monoamino polyglycerol dendrons and dendritic triblock amphiphiles. Eur. J. Org. Chem. 2008, 53–63 (2008)Google Scholar
  159. 159.
    Haag, R., Sunder, A., Stumbé, J.-F.: An approach to glycerol dendrimers and pseudo-dendritic polyglycerols. J. Am. Chem. Soc. 122, 2954–2955 (2000)Google Scholar
  160. 160.
    Sunder, A., Krämer, M., Hanselmann, R., Mülhaupt, R., Frey, H.: Molecular nanocapsules based on amphiphilic hyperbranched polyglycerols. Angew. Chem. Int. Ed. Engl. 38, 3552–3555 (1999)PubMedGoogle Scholar
  161. 161.
    Wilms, D., et al.: Hyperbranched polyglycerols with elevated molecular weights: a facile two-step synthesis protocol based on polyglycerol macroinitiators. Macromolecules 42, 3230–3236 (2009)Google Scholar
  162. 162.
    Barriau, E., et al.: Systematic investigation of functional core variation within hyperbranched polyglycerols. J. Polym. Sci. A1 46, 2049–2061 (2008)Google Scholar
  163. 163.
    Roller, S., Zhou, H., Haag, R.: High-loading polyglycerol supported reagents for Mitsunobu- and acylation-reactions and other useful polyglycerol derivatives. Mol. Divers. 9, 305–316 (2005)PubMedGoogle Scholar
  164. 164.
    Kainthan, R.K., Janzen, J., Levin, E., Devine, D.V., Brooks, D.E.: Biocompatibility testing of branched and linear polyglycidol. Biomacromolecules 7, 703–709 (2006)PubMedGoogle Scholar
  165. 165.
    Kainthan, R.K., Hester, S.R., Levin, E., Devine, D.V., Brooks, D.E.: In vitro biological evaluation of high molecular weight hyperbranched polyglycerols. Biomaterials 28, 4581–4590 (2007)PubMedGoogle Scholar
  166. 166.
    Kainthan, R.K., Brooks, D.E.: In vivo biological evaluation of high molecular weight hyperbranched polyglycerols. Biomaterials 28, 4779–4787 (2007)PubMedGoogle Scholar
  167. 167.
    Calderón, M., Quadir, M.A., Sharma, S.K., Haag, R.: Dendritic polyglycerols for biomedical applications. Adv. Mater. 22, 190–218 (2010)PubMedGoogle Scholar
  168. 168.
    Calderón, M., Graeser, R., Kratz, F., Haag, R.: Development of enzymatically cleavable prodrugs derived from dendritic polyglycerol. Bioorg. Med. Chem. Lett. 19, 3725–3728 (2009)PubMedGoogle Scholar
  169. 169.
    Calderón, M., et al.: Development of efficient acid cleavable multifunctional prodrugs derived from dendritic polyglycerol with a poly(ethylene glycol) shell. J. Control. Release 151, 295–301 (2011)PubMedGoogle Scholar
  170. 170.
    Papp, I., Dernedde, J., Enders, S., Haag, R.: Modular synthesis of multivalent glycoarchitectures and their unique selectin binding behavior. Chem. Commun. 4, 5851–5853 (2008)Google Scholar
  171. 171.
    Türk, H., Haag, R., Alban, S.: Dendritic polyglycerol sulfates as new heparin analogues and potent inhibitors of the complement system. Bioconjug. Chem. 15, 162–167 (2003)Google Scholar
  172. 172.
    Dernedde, J., et al.: Dendritic polyglycerol sulfates as multivalent inhibitors of inflammation. Proc. Natl. Acad. Sci. U. S. A. 44, 19679–19684 (2010)Google Scholar
  173. 173.
    Steinhilber, D., et al.: Synthesis, reductive cleavage, and cellular interaction studies of biodegradable polyglycerol nanogels. Adv. Funct. Mater. 20, 4133–4138 (2010)Google Scholar
  174. 174.
    Sisson, A.L., et al.: Biocompatible functionalized polyglycerol microgels with cell penetrating properties. Angew. Chem. Int. Ed. Engl. 48, 7540–7545 (2009)PubMedGoogle Scholar
  175. 175.
    Sisson, A.L., Papp, I., Landfester, K., Haag, R.: Functional nanoparticles from dendritic precursors: hierarchical assembly in miniemulsion. Macromolecules 42, 556–559 (2009)Google Scholar
  176. 176.
    Luxenhofer, R., et al.: Poly(2-oxazoline)s as polymer therapeutics. Macromol. Rapid Comm. 33, 1613–1631 (2012)Google Scholar
  177. 177.
    Viegas, T.X., et al.: Polyoxazoline: chemistry, properties, and applications in drug delivery. Bioconjugate Chem. 22, 976–986 (2011)Google Scholar
  178. 178.
    Knop, K., Hoogenboom, R., Fischer, D., Schubert, U.S.: Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew. Chem. Int. Ed. Engl. 49, 6288–6308 (2010)PubMedGoogle Scholar
  179. 179.
    Kempe, K., et al.: Multifunctional poly(2-oxazoline) nanoparticles for biological applications. Macromol. Rapid Comm. 31, 1869–1873 (2010)Google Scholar
  180. 180.
    Luxenhofer, R., et al.: Structure-property relationship in cytotoxicity and cell uptake of poly(2-oxazoline) amphiphiles. J. Control. Release 153, 73–82 (2011)PubMedGoogle Scholar
  181. 181.
    Donev, R., Koseva, N., Petrov, P., Kowalczuk, A., Thome, J.: Characterisation of different nanoparticles with a potential use for drug delivery in neuropsychiatric disorders. World J. Biol. Psychiatry 12, 44–51 (2011)PubMedGoogle Scholar
  182. 182.
    Tong, J., et al.: Neuronal uptake and intracellular superoxide scavenging of a fullerene (C60)-poly(2-oxazoline)s nanoformulation. Biomaterials 32, 3654–3665 (2011)PubMedGoogle Scholar
  183. 183.
    Viegas, T.X., et al.: Polyoxazoline: chemistry, properties, and applications in drug delivery. Bioconjug. Chem. 22, 976–986 (2011)PubMedGoogle Scholar
  184. 184.
    Wang, X., et al.: Synthesis, characterization and biocompatibility of poly(2-ethyl-2-oxazoline)-poly(D, L-lactide)-poly(2-ethyl-2-oxazoline) hydrogels. Acta Biomater. 7, 4149–4159 (2011)PubMedGoogle Scholar
  185. 185.
    Wang, C.-H., et al.: Extended release of bevacizumab by thermosensitive biodegradable and biocompatible hydrogel. Biomacromolecules 13, 40–48 (2012)PubMedGoogle Scholar
  186. 186.
    Cheon Lee, S., Kim, C., Chan Kwon, I., Chung, H., Young Jeong, S.: Polymeric micelles of poly(2- ethyl-2-oxazoline)-block-poly(epsilon-caprolactone) copolymer as a carrier for paclitaxel. J. Control. Release 89, 437–446 (2003)PubMedGoogle Scholar
  187. 187.
    Konradi, R., Pidhatika, B., Mühlebach, A., Textor, M.: Poly-2-methyl-2-oxazoline: a peptide-like polymer for protein-repellent surfaces. Langmuir 24, 613–616 (2008)PubMedGoogle Scholar
  188. 188.
    Pidhatika, B., et al.: The role of the interplay between polymer architecture and bacterial surface properties on the microbial adhesion to polyoxazoline-based ultrathin films. Biomaterials 31, 9462–9472 (2010)PubMedGoogle Scholar
  189. 189.
    Zhang, N., et al.: Tailored poly(2-oxazoline) polymer brushes to control protein adsorption and cell adhesion. Macromol. Biosci. 12, 926–936 (2012)PubMedGoogle Scholar
  190. 190.
    Wang, H., Li, L., Tong, Q., Yan, M.: Evaluation of photochemically immobilized poly(2-ethyl-2-oxazoline) thin films as protein-resistant surfaces. ACS Appl. Mater. Interfaces 3, 3463–3471 (2011)PubMedGoogle Scholar
  191. 191.
    Woodle, M.C., Engbers, C.M., Zalipsky, S.: New amphipathic polymer-lipid conjugates forming long-circulating reticuloendothelial system-evading liposomes. Bioconjug. Chem. 5, 493–496 (1994)PubMedGoogle Scholar
  192. 192.
    Zalipsky, S., Hansen, C.B., Oaks, J.M., Allen, T.M.: Evaluation of blood clearance rates and biodistribution of poly(2-oxazoline)-grafted liposomes. J. Pharm. Sci. 85, 133–137 (1996)PubMedGoogle Scholar
  193. 193.
    Gaertner, F.C., Luxenhofer, R., Blechert, B., Jordan, R., Essler, M.: Synthesis, biodistribution and excretion of radiolabeled poly(2-alkyl-2-oxazoline)s. J. Control. Release 119, 291–300 (2007)PubMedGoogle Scholar
  194. 194.
    Goddard, P., Hutchinson, L.: Soluble polymeric carriers for drug delivery. Part 2. Preparation and in vivo behaviour of N-acylethylenimine copolymers. J. Control. Release 10, 5–16 (1989)Google Scholar
  195. 195.
    Luxenhofer, R., et al.: Doubly amphiphilic poly(2-oxazoline)s as high-capacity delivery systems for hydrophobic drugs. Biomaterials 31, 4972–4979 (2010)PubMedGoogle Scholar
  196. 196.
    Delgado, A.V., González-Caballero, F., Hunter, R.J., Koopal, L.K., Lyklema, J.: Measurement and interpretation of electrokinetic phenomena. J. Colloid Interface Sci. 309, 194–224 (2007)PubMedGoogle Scholar
  197. 197.
    Rausch, K., Reuter, A., Fischer, K., Schmidt, M.: Evaluation of nanoparticle aggregation in human blood serum. Biomacromolecules 11, 2836–2839 (2010)Google Scholar
  198. 198.
    Olsen, S.N.: Applications of isothermal titration calorimetry to measure enzyme kinetics and activity in complex solutions. Thermochim. Acta 448, 12–18 (2006)Google Scholar
  199. 199.
    Gourishankar, A., Shukla, S., Ganesh, K.N., Sastry, M.: Isothermal titration calorimetry studies on the binding of DNA bases and PNA base monomers to gold nanoparticles. J. Am. Chem. Soc. 126, 13186–13187 (2004)PubMedGoogle Scholar
  200. 200.
    Cedervall, T., et al.: Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc. Natl. Acad. Sci. U. S. A. 104, 2050–2055 (2007)PubMedGoogle Scholar
  201. 201.
    Tenzer, S., et al.: Nanoparticle size is a critical physicochemical determinant of the human blood plasma corona: a comprehensive quantitative proteomic analysis. ACS Nano 5, 7155–7167 (2011)PubMedGoogle Scholar
  202. 202.
    Ghoroghchian, P.P., Therien, M.J., Hammer, D.A.: In vivo fluorescence imaging: a personal perspective. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 1, 156–167 (2009)PubMedGoogle Scholar
  203. 203.
    Herzog, H., Rösch, F.: PET- und SPECT-Technik: Chemie und Physik der Bildgebung. Pharm. Unserer Zeit 34, 468–473 (2005)PubMedGoogle Scholar
  204. 204.
    Herth, M.M., et al.: Radioactive labeling of defined HPMA-based polymeric structures using [18F]FETos for in vivo imaging by positron emission tomography. Biomacromolecules 10(4), 1697–1703 (2009)PubMedGoogle Scholar
  205. 205.
    Devaraj, N.K., Keliher, E.J., Thurber, G.M., Nahrendorf, M., Weissleder, R.: 18F labeled nanoparticles for in vivo PET-CT imaging. Bioconjugate Chem. 20, 397–401 (2009)Google Scholar
  206. 206.
    Herth, M.M., Barz, M., Jahn, M., Zentel, R., Rösch, F.: 72/74As-labeling of HPMA based polymers for long-term in vivo PET imaging. Bioorg. Med. Chem. Lett. 20, 5454–5458 (2010)PubMedGoogle Scholar
  207. 207.
    Fujita, Y., Taguchi, H.: Current status of multiple antigen-presenting peptide vaccine systems: application of organic and inorganic nanoparticles. Chem. Cent. J. 5, 1–8 (2011)Google Scholar
  208. 208.
    Vogel, F.R.: Immunologic adjuvants for modern vaccine formulations. Ann. N. Y. Acad. Sci. 754, 153–160 (1995)PubMedGoogle Scholar
  209. 209.
    Petrovsky, N., Aguilar, J.: Vaccine adjuvants: current state and future trends. Immunol. Cell Biol. 82, 488–496 (2004)PubMedGoogle Scholar
  210. 210.
    Panyam, J., Labhasetwar, V.: Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv. Drug Deliv. Rev. 55, 329–347 (2003)PubMedGoogle Scholar
  211. 211.
    Lee, Y.-R., Lee, Y.-H., et al.: Biodegradable nanoparticles containing TLR3 or TLR9 agonists together with antigen enhance MHC-restricted presentation of the antigen. Arch. Pharm. Res. 33, 1859–1866 (2010)PubMedGoogle Scholar
  212. 212.
    Stone, G.W., et al.: Nanoparticle-delivered multimeric soluble CD40L DNA combined with Toll-like receptor agonists as a treatment for melanoma. PLoS One 4, e7334 (2009)PubMedGoogle Scholar
  213. 213.
    Kasturi, S.P., et al.: Programming the magnitude and persistence of antibody responses with innate immunity. Nature 470, 543–547 (2011)PubMedGoogle Scholar
  214. 214.
    Malyala, P., O’Hagan, D.T., Singh, M.: Enhancing the therapeutic efficacy of CpG oligonucleotides using biodegradable microparticles. Adv. Drug Deliv. Rev. 61, 218–225 (2009)PubMedGoogle Scholar
  215. 215.
    O’Hagan, D.T., Singh, M., Ulmer, J.B.: Microparticle-based technologies for vaccines. Methods 40, 10–19 (2006)PubMedGoogle Scholar
  216. 216.
    Sherman, M. R. et al.: Conjugation of high-molecular weight poly(ethylene glycol) to cytokines: granulocyte-macrophage colony-stimulating factors as model substrates. ACS Symposium Series, Vol. 680, pp. 155–169. (1997)Google Scholar
  217. 217.
    Alexis, F., Pridgen, E., Molnar, L.K., Farokhzad, O.C.: Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol. Pharm. 5, 505–515 (2008)PubMedGoogle Scholar
  218. 218.
    Yang, Y., Huang, C.-T., Huang, X., Pardoll, D.M.: Persistent Toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance. Nat. Immunol. 5, 508–515 (2004)PubMedGoogle Scholar
  219. 219.
    Galloway, A.L., et al.: Development of a nanoparticle-based influenza vaccine using the PRINT® technology. Nanomedicine 9(4), 523–531 (2013)PubMedGoogle Scholar
  220. 220.
    Demento, S.L., et al.: TLR9-targeted biodegradable nanoparticles as immunization vectors protect against West Nile encephalitis. J. Immunol. 185, 2989–2997 (2010)PubMedGoogle Scholar
  221. 221.
    Tyagi, R.K., Garg, N.K., Sahu, T.: Vaccination strategies against malaria: novel carrier(s) more than a tour de force. J. Control. Release 162, 242–254 (2012)PubMedGoogle Scholar
  222. 222.
    Brandt, E.R., et al.: New multi-determinant strategy for a group A streptococcal vaccine designed for the Australian Aboriginal population. Nat. Med. 6, 455–459 (2000)PubMedGoogle Scholar
  223. 223.
    Shi, L., et al.: Pharmaceutical and immunological evaluation of a single-shot hepatitis B vaccine formulated with PLGA microspheres. J. Pharm. Sci. 91, 1019–1035 (2002)PubMedGoogle Scholar
  224. 224.
    Pejawar-Gaddy, S., et al.: Generation of a tumor vaccine candidate based on conjugation of a MUC1 peptide to polyionic papillomavirus virus-like particles. Cancer Immunol. Immunother. 59, 1685–1696 (2010)PubMedGoogle Scholar
  225. 225.
    Sundgren, A., Barchi, J.: Varied presentation of the Thomsen–Friedenreich disaccharide tumor-associated carbohydrate antigen on gold nanoparticles. Carbohydr. Res. 343, 1594–1604 (2008)PubMedGoogle Scholar
  226. 226.
    Monzavi-Karbassi, B., Pashov, A., Jousheghany, F., Artaud, C., Kieber-Emmons, T.: Evaluating strategies to enhance the anti-tumor immune response to a carbohydrate mimetic peptide vaccine. Int. J. Mol. Med. 17, 1045–1052 (2006)PubMedGoogle Scholar
  227. 227.
    Reddy, S., Swartz, M., Hubbell, J.: Targeting dendritic cells with biomaterials: developing the next generation of vaccines. Trends Immunol. 27, 573–579 (2006)PubMedGoogle Scholar
  228. 228.
    Demento, S.L., et al.: Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy. Vaccine 27, 3013–3021 (2009)PubMedGoogle Scholar
  229. 229.
    Hamdy, S., et al.: Co-delivery of cancer-associated antigen and Toll-like receptor 4 ligand in PLGA nanoparticles induces potent CD8+ T cell-mediated anti-tumor immunity. Vaccine 26, 5046–5057 (2008)PubMedGoogle Scholar
  230. 230.
    Barton, G.M., Medzhitov, R.: Control of adaptive immune responses by Toll-like receptors. Curr. Opin. Immunol. 14, 380–383 (2002)PubMedGoogle Scholar
  231. 231.
    Akagi, T., Baba, M., Akashi, M.: Biodegradable nanoparticles as vaccine adjuvants and delivery systems: regulation of immune responses by nanoparticle-based vaccine. Adv. Polym. Sci. 247, 31–64 (2011)Google Scholar
  232. 232.
    Lee, T.Y., et al.: Oral administration of poly-gamma-glutamate induces TLR4- and dendritic cell-dependent antitumor effect. Cancer Immunol Imm. 58, 1781–1794 (2009)Google Scholar
  233. 233.
    Yoshida, M., Babensee, J.E.: Poly(lactic-co-glycolic acid) enhances maturation of human monocyte-derived dendritic cells. J. Biomed. Mater. Res. A 71, 45–54 (2004)PubMedGoogle Scholar
  234. 234.
    Tamayo, I., et al.: Poly(anhydride) nanoparticles act as active Th1 adjuvants through Toll-like receptor exploitation. Clin. Vaccine Immunol. 17, 1356–1362 (2010)PubMedGoogle Scholar
  235. 235.
    Copland, M.J., et al.: Liposomal delivery of antigen to human dendritic cells. Vaccine 21, 883–890 (2003)PubMedGoogle Scholar
  236. 236.
    Matsusaki, M., et al.: Nanosphere induced gene expression in human dendritic cells. Nano Lett. 5, 2168–2173 (2005)PubMedGoogle Scholar
  237. 237.
    Kwon, Y.J., Standley, S.M., Goh, S.L., Fréchet, J.M.J.: Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles. J. Control. Release 105, 199–212 (2005)PubMedGoogle Scholar
  238. 238.
    Sun, H., Pollock, K.G.J., Brewer, J.M.: Analysis of the role of vaccine adjuvants in modulating dendritic cell activation and antigen presentation in vitro. Vaccine 21, 849–855 (2003)PubMedGoogle Scholar
  239. 239.
    Moon, H.-J., et al.: Mucosal immunization with recombinant influenza hemagglutinin protein and poly gamma-glutamate/chitosan nanoparticles induces protection against highly pathogenic influenza A virus. Vet. Microbiol. 160, 277–289 (2012)PubMedGoogle Scholar
  240. 240.
    Geall, A., Verma, A.: Nonviral delivery of self-amplifying RNA vaccines. Proc. Natl. Acad. Sci. U. S. A. 109, 14604–14609 (2012)PubMedGoogle Scholar
  241. 241.
    Van den Berg, J.H., et al.: Shielding the cationic charge of nanoparticle-formulated dermal DNA vaccines is essential for antigen expression and immunogenicity. J. Control. Release 141, 234–240 (2010)PubMedGoogle Scholar
  242. 242.
    Varkouhi, A.K., Scholte, M., Storm, G., Haisma, H.J.: Endosomal escape pathways for delivery of biologicals. J. Control. Release 151, 220–228 (2011)PubMedGoogle Scholar
  243. 243.
    Krieg, A.M.: CpG motifs in bacterial DNA and their immune effects. Annu. Rev. Immunol. 20, 709–760 (2002)PubMedGoogle Scholar
  244. 244.
    Sudowe, S., et al.: Uptake and presentation of exogenous antigen and presentation of endogenously produced antigen by skin dendritic cells represent equivalent pathways for the priming of cellular immune responses following biolistic DNA immunization. Immunology 128, e193–e205 (2009)PubMedGoogle Scholar
  245. 245.
    Joshi, M.D., Unger, W.J., Storm, G., Van Kooyk, Y., Mastrobattista, E.: Targeting tumor antigens to dendritic cells using particulate carriers. J. Control. Release 161, 25–37 (2012)PubMedGoogle Scholar
  246. 246.
    Arigita, C., et al.: Liposomal meningococcal B vaccination: role of dendritic cell targeting in the development of a protective immune response. Infect. Immun. 71, 5210–5218 (2003)PubMedGoogle Scholar
  247. 247.
    Espuelas, S., Haller, P., Schuber, F., Frisch, B.: Synthesis of an amphiphilic tetraantennary mannosyl conjugate and incorporation into liposome carriers. Bioorg. Med. Chem. Lett. 13, 2557–2560 (2003)PubMedGoogle Scholar
  248. 248.
    Espuelas, S., Thumann, C., Heurtault, B., Schuber, F., Frisch, B.: Influence of ligand valency on the targeting of immature human dendritic cells by mannosylated liposomes. Bioconjug. Chem. 19, 2385–2393 (2008)PubMedGoogle Scholar
  249. 249.
    Sheng, K.-C., et al.: Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo. Eur. J. Immunol. 38, 424–436 (2008)PubMedGoogle Scholar
  250. 250.
    Chenevier, P., et al.: Grafting of synthetic mannose receptor-ligands onto onion vectors for human dendritic cells targeting. Chem. Commun. 20, 2446–2447 (2002)Google Scholar
  251. 251.
    Saraogi, G.K., et al.: Mannosylated gelatin nanoparticles bearing isoniazid for effective management of tuberculosis. J. Drug Target. 19, 219–227 (2011)PubMedGoogle Scholar
  252. 252.
    Brandhonneur, N., et al.: Specific and non-specific phagocytosis of ligand-grafted PLGA microspheres by macrophages. Eur. J. Pharm. Sci. 36, 474–485 (2009)PubMedGoogle Scholar
  253. 253.
    Hamdy, S., Haddadi, A., Shayeganpour, A., Samuel, J., Lavasanifar, A.: Activation of antigen-specific T cell-responses by mannan-decorated PLGA nanoparticles. Pharm. Res. 28, 2288–2301 (2011)PubMedGoogle Scholar
  254. 254.
    Raghuwanshi, D., Mishra, V., Suresh, M.R., Kaur, K.: A simple approach for enhanced immune response using engineered dendritic cell targeted nanoparticles. Vaccine 30, 7292–7299 (2012)PubMedGoogle Scholar
  255. 255.
    Fehr, T., Skrastina, D., Pumpens, P., Zinkernagel, R.M.: T cell-independent type I antibody response against B cell epitopes expressed repetitively on recombinant virus particles. Proc. Natl. Acad. Sci. U. S. A. 95, 9477–9481 (1998)PubMedGoogle Scholar
  256. 256.
    Brinãs, R.P., et al.: Design and synthesis of multifunctional gold nanoparticles bearing tumor-associated glycopeptide antigens as potential cancer vaccines. Bioconjug. Chem. 23, 1513–1523 (2012)PubMedGoogle Scholar
  257. 257.
    Hoffmann-Röder, A., et al.: Synthetic antitumor vaccines from tetanus toxoid conjugates of MUC1 glycopeptides with the Thomsen-Friedenreich antigen and a fluorine-substituted analogue. Angew. Chem. Int. Ed. Engl. 49, 8498–8503 (2010)PubMedGoogle Scholar
  258. 258.
    Gaidzik, N., et al.: Synthetic antitumor vaccines containing MUC1 glycopeptides with two immunodominant domains-induction of a strong immune response against breast tumor tissues. Angew. Chem. Int. Ed. Engl. 50, 9977–9981 (2011)PubMedGoogle Scholar
  259. 259.
    Cai, H., et al.: Variation of the glycosylation pattern in MUC1 glycopeptide BSA vaccines and its influence on the immune response. Angew. Chem. Int. Ed. Engl. 51, 1719–1723 (2012)PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Philipp Heller
    • 1
  • David Huesmann
    • 1
  • Martin Scherer
    • 1
  • Matthias Barz
    • 1
  1. 1.Institute of Organic ChemistryJohannes Gutenberg-University MainzMainzGermany

Personalised recommendations