Targeted, Multifunctional Hydrogel Nanoparticles for Imaging and Treatment of Cancer

Chapter
Part of the Nanostructure Science and Technology book series (NST)

Abstract

Use of nanoparticles as a platform for carrying drugs, image contrast agents, or both has been considered to be a revolutionary approach for cancer diagnosis and therapy. Especially, hydrogel nanoparticles have drawn considerable interest as a very promising platform because of their favorable characteristics, based on the conceptual combination of nanoparticle and hydrogel. Nanoparticles can carry high payloads and target selectively to tumors because of their nanosize and engineering capability. The hydrogel characteristics, including hydrophilicity and reversible, stimuli-responsive swelling/deswelling, enable long plasma circulation times and controlled drug release. Hydrogel nanoparticles made of natural, synthetic, or combinations of both polymers have been designed, prepared, and applied for treatment and imaging of cancer with various therapeutic and imaging modalities. This chapter describes various types of hydrogel nanoparticles developed for cancer applications and their preparation methods and analyzes their characteristics which make them suitable for cancer therapy and imaging. It also presents selected applications of hydrogel nanoparticles for imaging (for diagnosis and surgical delineation) and therapeutic modalities as well as for integrated therapy and imaging.

References

  1. 1.
    American Cancer Society (2010) Cancer facts & figures 2010. American Cancer Society, AtlantaGoogle Scholar
  2. 2.
    Nimsky C, Ganslandt O, Kober H, Buchfelder M, Fahlbusch R (2001) Intraoperative magnetic resonance imaging combined with neuronavigation: a new concept. Neurosurgery 48:1082–1089CrossRefGoogle Scholar
  3. 3.
    Izquierdo MA, Scheffer GL, Flens MJ, Shoemaker RH, Rome LH, Scheper RJ (1996) Relationship of LRP-human major vault protein to in vitro and clinical resistance to anticancer drugs. Cytotechnology 19:191–197CrossRefGoogle Scholar
  4. 4.
    Gatmaitan ZC, Arias IM (1993) Structure and function of P-glycoprotein in normal liver and small intestine. Adv Pharmacol 24:77–97CrossRefGoogle Scholar
  5. 5.
    Allen TM (2002) Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer 2:750–763CrossRefGoogle Scholar
  6. 6.
    Maeda H (2001) The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 41:189–207CrossRefGoogle Scholar
  7. 7.
    Hong S, Leroueil PR, Majoros IJ, Orr BG, Baker JR, Holl MMB (2007) The binding avidity of a nanoparticle-based multivalent targeted drug delivery platform. Chem Biol 14:107–115CrossRefGoogle Scholar
  8. 8.
    Harrell JA, Kopelman R (2000) Biocompatible probes measure intracellular activity. Biophotonics Int 7:22–24Google Scholar
  9. 9.
    Xu H, Buck SM, Kopelman R, Philbert MA, Brasuel M, Ross B, Rehemtulla A, Festschrift J (2004) Photo-excitation based nano-explorers: chemical analysis inside live cells and photodynamic therapy. Isr J Chem 44:317–337CrossRefGoogle Scholar
  10. 10.
    Ross B, Rehemtulla A, Koo Y-EL, Reddy R, Kim G, Behrend C, Buck S, Schneider RJ, Philbert MA, Weissleder R, Kopelman R (2004) Photonic and magnetic nanoexplorers for biomedical use: from subcellular imaging to cancer diagnostics and therapy. Proc SPIE 5331:76–83CrossRefGoogle Scholar
  11. 11.
    Kopelman R, Koo YL, Philbert M, Moffat BA, Reddy GR, McConville P, Hall DE, Chenevert TL, Bhojani MS, Buck SM, Rehemtulla A, Ross BD (2005) Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer. J Magn Magn Mater 293:404–410CrossRefGoogle Scholar
  12. 12.
    Reddy GR, Bhojani MS, McConville P, Moody J, Moffat BA, Hall DE, Kim G, Koo Y-E, Woolliscroft MJ, Sugai JV, Johnson TD, Philbert MA, Kopelman R, Rehemtulla A, Ross BD (2006) Vascular targeted nanoparticles for imaging and treatment of brain tumors. Clin Cancer Res 12:6677–6686CrossRefGoogle Scholar
  13. 13.
    Hamidi M, Azadi A, Rafiei P (2008) Hydrogel nanoparticles in drug delivery. Adv Drug Deliv Rev 60:1638–1649CrossRefGoogle Scholar
  14. 14.
    Kashyap N, Kumar N, Kumar MNVR (2005) Hydrogels for pharmaceutical and biomedical applications. Crit Rev Ther Drug Carrier Syst 22:107–149CrossRefGoogle Scholar
  15. 15.
    Koo Y-EL, Reddy GR, Bhojani M, Schneider R, Philbert MA, Rehemtulla A, Ross BD, Kopelman R (2006) Brain cancer diagnosis and therapy with nano-platforms. Adv Drug Deliv Rev 58:1556–1577CrossRefGoogle Scholar
  16. 16.
    Qiu Y, Park K (2001) Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev 53:321–339CrossRefGoogle Scholar
  17. 17.
    Koo Lee Y-E, Smith R, Kopelman R (2009) Nanoparticle PEBBLE sensors in live cells and in vivo. Annu Rev Anal Chem 2:57–76CrossRefGoogle Scholar
  18. 18.
    Lee KY, Mooney DJ (2001) Hydrogels for tissue engineering. Chem Rev 101:1869–1879CrossRefGoogle Scholar
  19. 19.
    Wu Y, MacKay JA, McDaniel JR, Chilkoti A, Clark RL (2009) Fabrication of elastin-like polypeptide nanoparticles for drug delivery by electrospraying. Biomacromolecules 10:19–24CrossRefGoogle Scholar
  20. 20.
    Maitra A (1984) Determination of size parameters of water-aerosol OT-oil reverse micelles from their nuclear magnetic resonance data. J Phys Chem 88:5122–5125CrossRefGoogle Scholar
  21. 21.
    Munshi N, De TK, Maitra A (1997) Size modulation of polymeric nanoparticles under controlled dynamics of microemulsion droplets. J Colloid Interface Sci 190:387–391CrossRefGoogle Scholar
  22. 22.
    Bharali DJ, Sahoo SK, Mozumdar S, Maitra A (2003) Cross-linked polyvinylpyrrolidone nanoparticles: a potential carrier for hydrophilic drugs. J Colloid Interface Sci 258:415–423CrossRefGoogle Scholar
  23. 23.
    Ohya Y, Shiratani M, Kobayashi H, Ouchi T (1994) Release behavior of 5-fluorouracil from chitosan-gel nanospheres immobilizing 5-fluorouracil coated with polysaccharides and their cell specific cytotoxicity. Pure Appl Chem A31:629–642Google Scholar
  24. 24.
    Pitarresi G, Craparo EF, Palumbo FS, Carlisi B, Giammona G (2007) Composite nanoparticles based on hyaluronic acid chemically cross-linked with α, β-polyaspartylhydrazide. Biomacromolecules 8:1890–1898CrossRefGoogle Scholar
  25. 25.
    Lee H, Mok H, Lee S, Oh Y-K, Park TG (2007) Target-specific intracellular delivery of siRNA using degradable hyaluronic acid nanogels. J Control Release 119:245–252CrossRefGoogle Scholar
  26. 26.
    Khdair A, Gerard B, Handa H, Mao G, Shekhar MPV, Panyam J (2008) Surfactant-polymer nanoparticles enhance the effectiveness of anticancer photodynamic therapy. Mol Pharm 5:795–807CrossRefGoogle Scholar
  27. 27.
    Jain A, Jain SK (2008) In vitro and cell uptake studies for targeting of ligand anchored nanoparticles for colon tumors. Eur J Pharm Sci 35:404–416CrossRefGoogle Scholar
  28. 28.
    Zhang H, Mardyani S, Chan WCW, Kumacheva E (2006) Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics. Biomacromolecules 7:1568–1572CrossRefGoogle Scholar
  29. 29.
    Zhou X, Liu B, Yu X, Zha X, Zhang X, Chen Y, Wang X, Jin Y, Wu Y, Chen Y, Shan Y, Chen Y, Liu J, Kong W, Shen J (2007) Controlled release of PEI/DNA complexes from mannose-bearing chitosan microspheres as a potent delivery system to enhance immune response to HBV DNA vaccine. J Control Release 121:200–207CrossRefGoogle Scholar
  30. 30.
    Boddohi S, Moore N, Johnson PA, Kipper MJ (2009) Polysaccharide-based polyelectrolyte complex nanoparticles from chitosan, heparin, and hyaluronan. Biomacromolecules 10:1402–1409CrossRefGoogle Scholar
  31. 31.
    Duceppe N, Tabrizian M (2009) Factors influencing the transfection efficiency of ultra low molecular weight chitosan/hyaluronic acid nanoparticles. Biomaterials 30:2625–2631CrossRefGoogle Scholar
  32. 32.
    Rajaonarivony M, Vauthier C, Couarraze G, Puisieux F, Couvreur P (1993) Development of a new drug carrier made from alginate. J Pharm Sci 82:912–917CrossRefGoogle Scholar
  33. 33.
    Sarmento B, Ribeiro AJ, Veiga F, Ferreira DC, Neufeld RJ (2007) Insulin-loaded nanoparticles are prepared by alginate ionotropic pregelation followed by chitosan polyelectrolyte complexation. J Nanosci Nanotechnol 7:2833–2841CrossRefGoogle Scholar
  34. 34.
    Ahmad Z, Sharma S, Khuller GK (2007) Chemotherapeutic evaluation of alginate nanoparticle-encapsulated azole antifungal and antitubercular drugs against murine tuberculosis. Nanomedicine 3:239–243Google Scholar
  35. 35.
    Besheer A, Hause G, Kressler J, Maeder K (2007) Hydrophobically modified hydroxyethyl starch: synthesis, characterization, and aqueous self-assembly into nano-sized polymeric micelles and vesicles. Biomacromolecules 8:359–367CrossRefGoogle Scholar
  36. 36.
    Hornig S, Heinze T (2008) Efficient approach to design stable water-dispersible nanoparticles of hydrophobic cellulose esters. Biomacromolecules 9:1487–1492CrossRefGoogle Scholar
  37. 37.
    Akiyoshi K, Deguchi S, Moriguchi N, Yamaguchi S, Sunamoto J (1993) Self-aggregates of hydrophobized polysaccharides in water. Formation and characteristics of nanoparticles. Macromolecules 26:3062–3068CrossRefGoogle Scholar
  38. 38.
    Kuroda K, Fujimoto K, Sunamoto J, Akiyoshi K (2002) Hierarchical self-assembly of hydrophobically modified pullulan in water: gelation by networks of nanoparticles. Langmuir 18:3780–3786CrossRefGoogle Scholar
  39. 39.
    Choi KY, Lee S, Park K, Kim K, Park JH, Kwon IC, Jeong SY (2008) Preparation and characterization of hyaluronic acid-based hydrogel nanoparticles. J Phys Chem Solids 69:1591–1595CrossRefGoogle Scholar
  40. 40.
    Lee H, Ahn C-H, Park TG (2009) Poly[lactic-co-(glycolic acid)]-grafted hyaluronic acid copolymer micelle nanoparticles for target-specific delivery of doxorubicin. Macromol Biosci 9:336–342CrossRefGoogle Scholar
  41. 41.
    Yadav AK, Mishra P, Mishra AK, Mishra P, Jain S, Agrawal GP (2007) Development and characterization of hyaluronic acid-anchored PLGA nanoparticulate carriers of doxorubicin. Nanomedicine 3:246–257Google Scholar
  42. 42.
    Yadav AK, Mishra P, Jain S, Mishra P, Mishra AK, Agrawal GP (2008) Preparation and characterization of HA–PEG–PCL intelligent core–corona nanoparticles for delivery of doxorubicin. J Drug Target 16:464–478CrossRefGoogle Scholar
  43. 43.
    Westedt U, Kalinowski M, Wittmar M, Merdan T, Unger F, Fuchs J, Schäller S, Bakowsky U, Kissel T (2007) Poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) nanoparticles for local delivery of paclitaxel for restenosis treatment. J Control Release 119:41–51CrossRefGoogle Scholar
  44. 44.
    Vinogradov SV, Tatiana KTK, Kabanov AV (2002) Nanosized cationic hydrogels for drug delivery: preparation, properties and interactions with cells. Adv Drug Deliv Rev 54:135–147CrossRefGoogle Scholar
  45. 45.
    Nagahama K, Mori Y, Ohya Y, Ouchi T (2007) Biodegradable nanogel formation of polylactide-grafted dextran copolymer in dilute aqueous solution and enhancement of its stability by stereocomplexation. Biomacromolecules 8:2135–2141CrossRefGoogle Scholar
  46. 46.
    Oh JK, Lee DI, Park JM (2009) Biopolymer-based microgels/nanogels for drug delivery applications. Prog Polym Sci 34:1261–1282CrossRefGoogle Scholar
  47. 47.
    Huang G, Gao J, Hu ZB, John JVS, Ponder BC, Moro D (2004) Controlled drug release from hydrogel nanoparticle networks. J Control Release 94:303–311CrossRefGoogle Scholar
  48. 48.
    Vihola H, Laukkanen A, Hirvonen J, Tenhu H (2002) Binding and release of drugs into and from thermosensitive poly(N-vinyl caprolactam) nanoparticles. Eur J Pharm Sci 16:69–74CrossRefGoogle Scholar
  49. 49.
    Bodnar M, Hartmann JF, Borbely J (2006) Synthesis and study of cross-linked chitosan-N-poly(ethylene glycol) nanoparticles. Biomacromolecules 11:3030–3036CrossRefGoogle Scholar
  50. 50.
    Shen X, Zhang L, Jiang X, Hu Y, Guo J (2007) Reversible surface switching of nanogel triggered by external stimuli. Angew Chem Int Ed 46:7104–7107CrossRefGoogle Scholar
  51. 51.
    Coester CJ, Langer K, Von Briesen H, Kreuter J (2000) Gelatin nanoparticles by two step desolvation a new preparation method, surface modifications and cell uptake. J Microencapsul 17:187–193CrossRefGoogle Scholar
  52. 52.
    Maham A, Tang Z, Wu H, Wang J, Lin Y (2009) Protein-based nanomedicine platforms for drug delivery. Small 5:1706–1721CrossRefGoogle Scholar
  53. 53.
    Davis ME, Chen Z, Shin DM (2008) Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7:771–782CrossRefGoogle Scholar
  54. 54.
    Hah HJ, Kim G, Koo Lee Y-E, Orringer DA, Sagher O, Philbert MA, Kopelman R (2011) Methylene blue-conjugated hydrogel nanoparticles and tumor-cell targeted photodynamic therapy. Macromol Biosci 11:90–99CrossRefGoogle Scholar
  55. 55.
    Montet X, Funovics M, Montet-Abou K, Weissleder R, Josephson L (2006) Multivalent effects of RGD peptides obtained by nanoparticle display. J Med Chem 49:6087–6093CrossRefGoogle Scholar
  56. 56.
    Kataoka K, Miyazaki H, Bunya M, Okano T, Sakurai Y (1998) Totally synthetic polymer gels responding to external glucose concentration: their preparation and application to on-off regulation of insulin release. J Am Chem Soc 120:12694–12695CrossRefGoogle Scholar
  57. 57.
    Miyata T, Asami N, Uragami T (1999) A reversibly antigen-responsive hydrogel. Nature 399:766–769CrossRefGoogle Scholar
  58. 58.
    Bromberg LE, Ron ES (1998) Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery. Adv Drug Deliv Rev 31:197–221CrossRefGoogle Scholar
  59. 59.
    Tanaka T, Nishio I, Sun S-T, Ueno-Nishio S (1982) Collapse of gels in an electric field. Science 218:467–469CrossRefGoogle Scholar
  60. 60.
    Suzuki A, Tanaka T (1990) Phase transition in polymer gels induced by visible light. Nature 346:345–347CrossRefGoogle Scholar
  61. 61.
    Mamada A, Tanaka T, Kungwatchakun D, Irie M (1990) Photoinduced phase-transition of gel. Macromolecules 23:1517–1519CrossRefGoogle Scholar
  62. 62.
    Duncan R (2006) Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer 6:688–701CrossRefGoogle Scholar
  63. 63.
    Wang J, Gan D, El-Sayed MA (2001) Temperature-jump investigations of the kinetics of hydrogel nanoparticle volume phase transitions. J Am Chem Soc 123:11284–11289CrossRefGoogle Scholar
  64. 64.
  65. 65.
    Service RF (2010) Nanotechnology: nanoparticle Trojan horses gallop from the lab into the clinic. Science 330:314–315CrossRefGoogle Scholar
  66. 66.
    Winer I, Wang S, Koo Lee Y-E, Fan W, Gong Y, Burgos-Ojeda D, Spahlinger G, Kopelman R, Buckanovich RJ (2010) F3-targeted cisplatin-hydrogel nanoparticles as an effective therapeutic that targets both murine and human ovarian tumor endothelial cells in vivo. Cancer Res 70:8674–8683CrossRefGoogle Scholar
  67. 67.
    Guowei D, Adriane K, Chen X, Jie C, Yinfeng L (2007) PVP magnetic nanospheres: biocompatibility, in vitro and in vivo bleomycin release. Int J Pharm 328:78–85CrossRefGoogle Scholar
  68. 68.
    Huang S-J, Sun S-L, Feng T-H, Sung K-H, Lui W-L, Wang L-F (2009) Folate-mediated chondroitin sulfate-Pluronic® 127 nanogels as a drug carrier. Eur J Pharm Sci 38:64–73CrossRefGoogle Scholar
  69. 69.
    Li X, Li R, Qian X, Ding Y, Tu Y, Guo R, Hu Y, Jiang X, Guo W, Liu B (2008) Superior antitumor efficiency of cisplatin-loaded nanoparticles by intratumoral delivery with decreased tumor metabolism rate. Eur J Pharm Biopharm 70:726–734CrossRefGoogle Scholar
  70. 70.
    Hidaka M, Kanematsu T, Ushio K, Sunamoto J (2006) Selective and effective cytotoxicity of folic acid-conjugated cholesteryl pullulan hydrogel nanoparticles complexed with doxorubicin in in vitro and in vivo studies. J Bioact Compat Polym 21:591–602CrossRefGoogle Scholar
  71. 71.
    Susa M, Iyer AK, Ryu K, Hornicek FJ, Mankin H, Amiji MM, Duan ZF (2009) Doxorubicin loaded polymeric nanoparticulate delivery system to overcome drug resistance in osteosarcoma. BMC Cancer 9:399CrossRefGoogle Scholar
  72. 72.
    Christian S, Pilch J, Akerman ME, Porkka K, Laakkonen P, Ruoslahti E (2003) Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels. J Cell Biol 163:871–878CrossRefGoogle Scholar
  73. 73.
    Huang Y, Shi H, Zhou H, Song X, Yuan S, Luo Y (2006) The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin. Blood 107:3564–3571CrossRefGoogle Scholar
  74. 74.
    Liechty WB, Kryscio DR, Slaughter BV, Peppas NA (2010) Polymers for drug delivery systems. Annu Rev Chem Biomol Eng 1:149–173CrossRefGoogle Scholar
  75. 75.
    Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49:6449–6465Google Scholar
  76. 76.
    Lee ES, Gao Z, Bae YH (2008) Recent progress in tumor pH targeting nanotechnology. J Control Release 132:164–170CrossRefGoogle Scholar
  77. 77.
    Park JH, Kwon S, Lee M, Chung H, Kim JH, Kim YS, Park RW, Kim IS, Seo SB, Kwon IC, Jeong SY (2006) Self-assembled nanoparticles based on glycol chitosan bearing hydrophobic moieties as carriers for doxorubicin: in vivo biodistribution and anti-tumor activity. Biomaterials 27:119–126CrossRefGoogle Scholar
  78. 78.
    Kim J-H, Kim Y-S, Park K, Lee S, Nam HY, Min KH, Jo HG, Park JH, Choi K, Jeong SY, Park R-W, Kim I-S, Kim K, Kwon IC (2008) Antitumor efficacy of cisplatin-loaded glycol chitosan nanoparticles in tumor-bearing mice. J Control Release 127:41–49CrossRefGoogle Scholar
  79. 79.
    Zhao ZM, He M, Yin LC, Bao J, Shi L, Wang B, Tang C, Yin C (2009) Biodegradable nanoparticles based on linoleic acid and poly(beta-malic acid) double grafted chitosan derivatives as carriers of anticancer drugs. Biomacromolecules 10:565–572CrossRefGoogle Scholar
  80. 80.
    Ray D, Mohapatra DK, Mohapatra RK, Mohanta GP, Sahoo PK (2008) Synthesis and colon-specific drug delivery of a poly(acrylic acid-co-acrylamide)/MBA nanosized hydrogel. J Biomater Sci Polym Ed 19:1487–1502CrossRefGoogle Scholar
  81. 81.
    Na K, Lee KH, Bae YH (2004) pH-sensitivity and pH-dependent interior structural change of self-assembled hydrogel nanoparticles of pullulan acetate/oligo-sulfonamide conjugate. J Control Release 97:513–525Google Scholar
  82. 82.
    Na K, Lee ES, Bae YH (2007) Self-organized nanogels responding to tumor extracellular pH: pH-dependent drug release and in vitro cytotoxicity against MCF-7 cells. Bioconjug Chem 18:1568–1574CrossRefGoogle Scholar
  83. 83.
    Zhang H-Z, Li X-M, Gao F-P, Liu L-R, Zhou Z-M, Zhang Q-Q (2010) Preparation of folate-modified pullulan acetate nanoparticles for tumor-targeted drug delivery. Drug Deliv 17:48–57CrossRefGoogle Scholar
  84. 84.
    Xu PS, Van Kirk EA, Murdoch WJ, Zhan YH, Isaak DD, Radosz M, Shen YQ (2006) Anticancer efficacies of cisplatin-releasing pH-responsive nanoparticles. Biomacromolecules 7:829–835CrossRefGoogle Scholar
  85. 85.
    Murthy N, Xu M, Schuck S, Kunisawa J, Shastri N, Frechet JM (2003) A macromolecular delivery vehicle for protein-based vaccines: acid-degradable protein-loaded microgels. Proc Natl Acad Sci USA 100:4995–5000CrossRefGoogle Scholar
  86. 86.
    Shi L, Khondee S, Linz TH, Berkland C (2008) Poly(N-vinylformamide) nanogels capable of pH-sensitive protein release. Macromolecules 41:6546–6554CrossRefGoogle Scholar
  87. 87.
    Fisher OZ, Peppas NA (2009) Polybasic nanomatrices prepared by UV-initiated photopolymerization. Macromolecules 42:3391–3398CrossRefGoogle Scholar
  88. 88.
    Owens DE, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102CrossRefGoogle Scholar
  89. 89.
    Fan L, Li F, Zhang H, Yukun Wang Y, Cheng C, Li X, Gu C-H, Qian Yang Q, Wu H, Zhang S (2010) Co-delivery of PDTC and doxorubicin by multifunctional micellar nanoparticles to achieve active targeted drug delivery and overcome multidrug resistance. Biomaterials 31:5634–5642CrossRefGoogle Scholar
  90. 90.
    Schafer FQ, Buettner GR (2001) Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 30:1191–1212CrossRefGoogle Scholar
  91. 91.
    Oh JK, Siegwart DJ, Lee H, Sherwood G, Peteanu L, Hollinger JO, Kataoka K, Matyjaszewski K (2007) Biodegradable nanogels prepared by atom transfer radical polymerization as potential drug delivery carriers: synthesis, biodegradation, in vitro release, and bioconjugation. J Am Chem Soc 129:5939–5945CrossRefGoogle Scholar
  92. 92.
    Shah S, Pal A, Rajiv Gude R, Devi S (2010) Synthesis and characterization of thermo-responsive copolymeric nanoparticles of poly(methyl methacrylate-co-N-vinylcaprolactam). Eur Polym J 46:958–967CrossRefGoogle Scholar
  93. 93.
    van den Brom CR, Anac I, Roskamp RF, Retsch M, Jonas U, Menges B, Preece JA (2010) The swelling behaviour of thermoresponsive hydrogel/silica nanoparticle composites. J Mater Chem 20:4827–4839CrossRefGoogle Scholar
  94. 94.
    Morimoto N, Qiu X-P, Winnik FM, Akiyoshi K (2008) Dual stimuli-responsive nanogels by self-assembly of polysaccharides lightly grafted with thiol-terminated poly(N-isopropylacrylamide) chains. Macromolecules 41:5985–5987CrossRefGoogle Scholar
  95. 95.
    Ma LW, Liu MZ, Liu HL, Chen J, Cui D (2010) In vitro cytotoxicity and drug release properties of pH- and temperature-sensitive core-shell hydrogel microspheres. Int J Pharm 385:86–91CrossRefGoogle Scholar
  96. 96.
    Fan L, Wu H, Zhang H, Li F, Yang T-H, Gu C-H, Yang Q (2008) Novel super pH-sensitive nanoparticles responsive to tumor extracellular pH. Carbohydr Polym 73:390–400CrossRefGoogle Scholar
  97. 97.
    Nezhadi SH, Choong PFM, Lotfipour F, Dass CR (2009) Gelatin-based delivery systems for cancer gene therapy. J Drug Target 17:731–738CrossRefGoogle Scholar
  98. 98.
    Patil SD, Rhodes DG, Burgess DJ (2005) DNA-based therapeutics and DNA delivery systems: a comprehensive review. AAPS J 7:E61–E77CrossRefGoogle Scholar
  99. 99.
    Kommareddy S, Amiji M (2007) Antiangiogenic gene therapy with systemically administered sFlt-1 plasmid DNA in engineered gelatin-based nanovectors. Cancer Gene Ther 14:488–498CrossRefGoogle Scholar
  100. 100.
    Kaul G, Amiji M (2005) Tumor-targeted gene delivery using poly(ethylene glycol)-modified gelatin nanoparticles: in vitro and in vivo studies. Pharm Res 22:951–961CrossRefGoogle Scholar
  101. 101.
    Susa M, Iyer AK, Ryu K, Choy E, Hornicek FJ, Mankin H, Milane L, Amiji MM, Duan Z (2010) Inhibition of ABCB1 (MDR1) expression by an siRNA nanoparticulate delivery system to overcome drug resistance in osteosarcoma. PLoS One 5:e10764CrossRefGoogle Scholar
  102. 102.
    Naeye B, Raemdonck K, Remaut K, Sproat B, Demeester J, De Smedt SC (2010) PEGylation of biodegradable dextran nanogels for siRNA delivery. Eur J Pharm Sci 40:342–351CrossRefGoogle Scholar
  103. 103.
    Dickerson EB, Blackburn WH, Smith MH, Kapa LB, Lyon LA, McDonald JF (2010) Chemosensitization of cancer cells by siRNA using targeted nanogel delivery. BMC Cancer 10:10CrossRefGoogle Scholar
  104. 104.
    Day AJ, Prestwich GD (2002) Hyaluronan-binding proteins: tying up the giant. J Biol Chem 277:4585–4588CrossRefGoogle Scholar
  105. 105.
    Ossipov DA (2010) Nanostructured hyaluronic acid-based materials for active delivery to cancer. Expert Opin Drug Deliv 7:681–703CrossRefGoogle Scholar
  106. 106.
    Cohen JA, Beaudette TT, Tseng WW, Bachelder EM, Mende I, Engleman EG, Frechet JMJ (2009) T-cell activation by antigen-loaded pH-sensitive hydrogel particles in vivo: the effect of particle size. Bioconjug Chem 20:111–119CrossRefGoogle Scholar
  107. 107.
    Fisher O, Kim T, Dietz S, Peppas NA (2009) Enhanced core hydrophobicity, functionalization and cell penetration of polybasic nanomatrices. Pharm Res 26:51–60CrossRefGoogle Scholar
  108. 108.
    Hu Y, Litwin T, Nagaraja AR, Kwong B, Katz J, Watson N, Irvine DJ (2007) Cytosolic delivery of membrane-impermeable molecules in dendritic cells using pH-responsive core-shell nanoparticles. Nano Lett 7:3056–3064CrossRefGoogle Scholar
  109. 109.
    Hasegawa K, Noguchi Y, Koizumi F, Uenaka A, Tanaka M, Shimono M, Nakamura H, Shiku H, Gnjatic S, Murphy R, Hiramatsu Y, Old LJ, Nakayama E (2006) In vitro stimulation of CD8 and CD4 T cells by dendritic cells loaded with a complex of cholesterol-bearing hydrophobized pullulan and NYESO-1 protein: identification of a new HLA-DR15-binding CD4 T-cell epitope. Clin Cancer Res 12:1921–1927CrossRefGoogle Scholar
  110. 110.
    Kawabata R, Wada H, Isobe M, Saika T, Sato S, Uenaka A, Miyata H, Yasuda T, Doki Y, Noguchi Y, Kumon H, Tsuji K, Iwatsuki K, Shiku H, Ritter G, Murphy R, Hoffman E, Old LJ, Monden M, Nakayama E (2007) Antibody response against NY-ESO-1 in CHPNY-ESO-1 vaccinated patients. Int J Cancer 120:2178–2184CrossRefGoogle Scholar
  111. 111.
    Shimizu T, Kishida T, Hasegawa U, Ueda Y, Imanishi J, Yamagishi H, Akiyoshi K, Otsuji E, Mazda O (2008) Nanogel DDS enables sustained release of IL-12 for tumor immunotherapy. Biochem Biophys Res Commun 367:330–335CrossRefGoogle Scholar
  112. 112.
    Severino D, Junqueira HC, Gugliotti M, Gabrielli DS, Baptista MS (2003) Influence of negatively charged interfaces on the ground and excited state properties of methylene blue. Photochem Photobiol 77:459–468CrossRefGoogle Scholar
  113. 113.
    Tanielian C, Heinrich G (1995) Effect of aggregation on the hematoporphyrin-sensitized production of singlet molecular oxygen. Photochem Photobiol 61:131–133CrossRefGoogle Scholar
  114. 114.
    Buytaert E, Dewaele M, Agostinis P (2007) Molecular effectors of multiple cell death pathways initiated by photodynamic therapy. Biochim Biophys Acta 1776:86–107Google Scholar
  115. 115.
    Tang W, Xu H, Park EJ, Philbert MA, Kopelman R (2008) Encapsulation of methylene blue in polyacrylamide nanoparticle platforms protects its photodynamic effectiveness. Biochem Biophys Res Commun 369:579–583CrossRefGoogle Scholar
  116. 116.
    Tang W, Xu H, Kopelman R, Philbert MA (2005) Photodynamic characterization and in vitro application of methylene blue-containing nanoparticle platforms. Photochem Photobiol 81:242–249CrossRefGoogle Scholar
  117. 117.
    Gao D, Agayan RR, Xu H, Philbert MA, Kopelman R (2006) Nanoparticles for two-photon photodynamic therapy in living cells. Nano Lett 6:2383–2386CrossRefGoogle Scholar
  118. 118.
    Gao D, Xu H, Philbert MA, Kopelman R (2007) Ultrafine hydrogel particles: synthetic approach and therapeutic application in living cells. Angew Chem 46:2224–2227CrossRefGoogle Scholar
  119. 119.
    Chen K, Preuß A, Hackbarth S, Wacker M, Langer K, Röder B (2009) Novel photosensitizer-protein nanoparticles for photodynamic therapy: photophysical characterization and in vitro investigations. J Photochem Photobiol B 96:66–74CrossRefGoogle Scholar
  120. 120.
    Rodrigues MMA, Simioni AR, Primo FL, Siqueira-Moura MP, Morais PC, Tedesco AC (2009) Preparation, characterization and in vitro cytotoxicity of BSA-based nanospheres containing nanosized magnetic particles and/or photosensitizer. J Magn Magn Mater 321:1600–1603CrossRefGoogle Scholar
  121. 121.
    Deda DK, Uchoa AF, Carita E, Baptista MS, Toma HE, Araki K (2009) A new micro/nanoencapsulated porphyrin formulation for PDT treatment. Int J Pharm 376:76–83CrossRefGoogle Scholar
  122. 122.
    Khdair A, Handa H, Mao G, Panyam J (2009) Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro. Eur J Pharm Biopharm 71:214–222CrossRefGoogle Scholar
  123. 123.
    Gabrielli D, Belisle E, Severino D, Kowaltowski AJ, Baptista MS (2004) Binding, aggregation and photochemical properties of methylene blue in mitochondrial suspensions. Photochem Photobiol 79:227–232CrossRefGoogle Scholar
  124. 124.
    Koo Lee Y-E, Kopelman R (2010) Multifunctional nanoparticles for targeted imaging and therapy of cancer. In: Bao Y, Dattelbaum AM, Tracy JB, Yin Y (eds) Multifunctional nanoparticle systems—coupled behavior and applications. Mat Res Soc Sym Proc 1257, 1257-O07-02Google Scholar
  125. 125.
    Song H-C, Na K, Park KH, Shin C-H, Bom H-S, Kang D, Kim S, Lee ES, Lee DH (2006) Intratumoral administration of rhenium-188-labeled pullulan acetate nanoparticles (PAN) in mice bearing CT-26 cancer cells for suppression of tumor growth. J Microbiol Biotechnol 16:1491–1498Google Scholar
  126. 126.
    Hallahan D, Geng L, Qu S, Scarfone C, Giorgio T, Donnelly E, Gao X, Clanton J (2003) Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels. Cancer Cell 3:63–74CrossRefGoogle Scholar
  127. 127.
    Moffat BA, Reddy GR, McConville P, Hall DE, Chenevert TL, Kopelman RR, Philbert M, Weissleder R, Rehemtulla A, Ross BD (2003) A novel polyacrylamide magnetic nanoparticle contrast agent for molecular imaging using MRI. Mol Imaging 2:324–332CrossRefGoogle Scholar
  128. 128.
    Ma H, Shiraishi K, Minowa T, Kawano K, Yokoyama M, Hattori Y, Maitani Y (2010) Accelerated blood clearance was not induced for a gadolinium-containing PEG-poly(L-lysine)-based polymeric micelle in mice. Pharm Res 27:296–302CrossRefGoogle Scholar
  129. 129.
    Banerjee T, Singh AK, Sharma RK, Maitra AN (2005) Labeling efficiency and biodistribution of Technetium-99m labeled nanoparticles: interference by colloidal tin oxide particles. Int J Pharm 289:189–195CrossRefGoogle Scholar
  130. 130.
    Sun G, Hagooly A, Xu J, Nystrom AM, Li ZC, Rossin R, Moore DA, Wooley KL, Welch MJ (2008) Facile, efficient approach to accomplish tunable chemistries and variable biodistributions for shell cross-linked nanoparticles. Biomacromolecules 9:1997–2006CrossRefGoogle Scholar
  131. 131.
    Sun G, Xu J, Hagooly A, Rossin R, Li Z, Moore DA, Hawker CJ, Welch MJ, Wooley KL (2007) Strategies for optimized radiolabeling of nanoparticles for in vivo PET Imaging. Adv Mater 19:3157–3162CrossRefGoogle Scholar
  132. 132.
    Orringer DA, Koo Y-EL, Chen T, Kim G, Hah H, Xu H, Wang S, Keep R, Philbert MA, Sagher O, Kopelman R (2009) In vitro characterization of a targeted, dye-loaded nanodevice for intraoperative tumor delineation. Neurosurgery 64:965–972CrossRefGoogle Scholar
  133. 133.
    Orringer DA, Sagher O, Kopelman R, Koo YE (2010) Dye-loaded nanoparticles. US patent US2010/0098637Google Scholar
  134. 134.
    Wu W, Aiello M, Zhou T, Berliner A, Banerjee P, Zhou S (2010) In-situ immobilization of quantum dots in polysaccharide-based nanogels for integration of optical pH-sensing, tumor cell imaging, and drug delivery. Biomaterials 31:3023–3031CrossRefGoogle Scholar
  135. 135.
    Kim JH, Kim YS, Kim S, Park JH, Kim K, Choi K, Chung H, Jeong SY, Park RW, Kim IS, Kwon IC (2006) Hydrophobically modified glycol chitosan nanoparticles as carriers for paclitaxel. J Control Release 111:228–234CrossRefGoogle Scholar
  136. 136.
    Yang SG, Chang JE, Shin B, Park S, Na K, Shim CK (2010) 99mTc-hematoporphyrin linked albumin nanoparticles for lung cancer targeted photodynamic therapy and imaging. J Mater Chem 20:9042–9046CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of ChemistryThe University of MichiganAnn ArborUSA

Personalised recommendations