Nanomedicine pp 365-384 | Cite as

Nanomedicine in Cancer Diagnosis and Therapy: Converging Medical Technologies Impacting Healthcare

  • Maya Thanou
  • Andrew D. Miller
Part of the Nanostructure Science and Technology book series (NST)


Nanomedicine is the application of nanotechnology to medicine. Nanomedicine aims to overcome unmet needs in disease management and treatment through interventions on the nanoscale that correlate with the operational scale of biological macromolecules inside cells. Although widely applicable for the diagnosis and treatment of many diseases nanomedicine is most progressed in research directed at the diagnosis and treatment of cancer. Today, researchers are constantly developing new nanomaterials, nanodevices, and nanoparticles with different applications in mind. Of particular interest here are nanoparticles that are genuine particles (approx 100 nm in dimension). These nanoparticles are intended to enable the functional delivery of therapeutic agents to disease-target cells for treatment and/or of imaging agents to disease-target cells for diagnosis. They are assembled typically from “tool-kits” of different chemical components that act collectively to overcome biological barriers (biobarriers). The functional capabilities of nanoparticles should vary according to functional requirements. Fortunately the nanoscale allows for an impressive level of diversity in capabilities to enable corresponding nanoparticles to address an equally diverse range of functional requirements. Therefore, nanoparticles are now considered appropriate vehicles to lead to an integrated, personalized approach to diagnosis and therapy in healthcare, most especially where future cancer disease management is concerned.


Nanomedicine Nanoparticles Cancer nanotechnology Triggerability Ultrasound 


  1. 1.
    Ferrari M (2005) Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 5(3):161–171. doi: 10.1038/nrc1566 Google Scholar
  2. 2.
    Srinivas PR, Barker P, Srivastava S (2002) Nanotechnology in early detection of cancer. Lab Investig J Tech Methods Pathol 82(5):657–662Google Scholar
  3. 3.
    Nie S, Xing Y, Kim GJ, Simons JW (2007) Nanotechnology applications in cancer. Annu Rev Biomed Eng 9:257–288. doi: 10.1146/annurev.bioeng.9.060906.152025 Google Scholar
  4. 4.
    Wang MD, Shin DM, Simons JW, Nie S (2007) Nanotechnology for targeted cancer therapy. Expert Rev Anticancer Ther 7(6):833–837. doi: 10.1586/14737140.7.6.833 Google Scholar
  5. 5.
    Anon (2007) Cancer nanotechnology: small, but heading for the big time. Nat Rev Drug Discov 6(3):174–175. doi: 10.1038/nrd2285 Google Scholar
  6. 6.
    EPT Nanomedicine (2009) Roadmaps in nanomedicine towards 2020. Accessed 22 June 2014
  7. 7.
    Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES (1999) Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286(5439):531–537Google Scholar
  8. 8.
    Ross DT, Scherf U, Eisen MB, Perou CM, Rees C, Spellman P, Iyer V, Jeffrey SS, Van de Rijn M, Waltham M, Pergamenschikov A, Lee JC, Lashkari D, Shalon D, Myers TG, Weinstein JN, Botstein D, Brown PO (2000) Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet 24(3):227–235. doi: 10.1038/73432 Google Scholar
  9. 9.
    Scherf U, Ross DT, Waltham M, Smith LH, Lee JK, Tanabe L, Kohn KW, Reinhold WC, Myers TG, Andrews DT, Scudiero DA, Eisen MB, Sausville EA, Pommier Y, Botstein D, Brown PO, Weinstein JN (2000) A gene expression database for the molecular pharmacology of cancer. Nat Genet 24(3):236–244. doi: 10.1038/73439 Google Scholar
  10. 10.
    Rubin MA (2001) Use of laser capture microdissection, cDNA microarrays, and tissue microarrays in advancing our understanding of prostate cancer. J Pathol 195(1):80–86. doi: 10.1002/path.892 Google Scholar
  11. 11.
    Evans WE, Relling MV (2004) Moving towards individualized medicine with pharmacogenomics. Nature 429(6990):464–468. doi: 10.1038/nature02626 Google Scholar
  12. 12.
    Petros WP, Evans WE (2004) Pharmacogenomics in cancer therapy: is host genome variability important? Trends Pharmacol Sci 25(9):457–464. doi: 10.1016/ Google Scholar
  13. 13.
    Hwang SR, Ku SH, Joo MK, Kim SH, Kwon IC (2014) Theranostic nanomaterials for image-guided gene therapy. MRS Bull 39(01):44–50Google Scholar
  14. 14.
    Sun NF, Liu ZA, Huang WB, Tian AL, Hu SY (2014) The research of nanoparticles as gene vector for tumor gene therapy. Crit Rev Oncol Hematol 89(3):352–357Google Scholar
  15. 15.
    Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG (2014) Non-viral vectors for gene-based therapy. Nat Rev Genet 15(8):541–555Google Scholar
  16. 16.
    Miller AD (2008) Towards safe nanoparticle technologies for nucleic acid therapeutics. Tumori 94(2):234–245Google Scholar
  17. 17.
    Kostarelos K, Miller AD (2005) Synthetic, self-assembly ABCD nanoparticles; a structural paradigm for viable synthetic non-viral vectors. Chem Soc Rev 34(11):970–994Google Scholar
  18. 18.
    Fletcher S, Ahmad A, Perouzel E, Heron A, Miller AD, Jorgensen MR (2006) In vivo studies of dialkynoyl analogues of DOTAP demonstrate improved gene transfer efficiency of cationic liposomes in mouse lung. J Med Chem 49:349–357Google Scholar
  19. 19.
    Fletcher S, Ahmad A, Perouzel E, Jorgensen MR, Miller AD (2006) A dialkanoyl analogue of DOPE improves gene transfer of lower-charged, cationic lipoplexes. Org Biomol Chem 4:196–199Google Scholar
  20. 20.
    Fletcher S, Ahmad A, Price WS, Jorgensen MR, Miller AD (2008) Biophysical properties of CDAN/DOPE-analogue lipoplexes account for enhanced gene delivery. Chembiochem 9(3):455–463Google Scholar
  21. 21.
    Miller AD (2003) The problem with cationic liposome/micelle-based non-viral vector systems for gene therapy. Curr Med Chem 10(14):1195–1211Google Scholar
  22. 22.
    Miller AD (2004) Gene therapy needs robust synthetic nonviral platform technologies. Chembiochem 5(1):53–54Google Scholar
  23. 23.
    Miller AD (2004) Nonviral liposomes. In: Springer CJ (ed) Methods in molecular medicine, vol 90. Humana Press, Totowa, pp 107–137Google Scholar
  24. 24.
    Oliver M, Jorgensen MR, Miller AD (2004) The facile solid-phase synthesis of cholesterol-based polyamine lipids. Tetrahedron Lett 45:3105–3108Google Scholar
  25. 25.
    Spagnou S, Miller AD, Keller M (2004) Lipidic carriers of siRNA: differences in the formulation, cellular uptake, and delivery with plasmid DNA. Biochemistry 43(42):13348–13356Google Scholar
  26. 26.
    Tagawa T, Manvell M, Brown N, Keller M, Perouzel E, Murray KD, Harbottle RP, Tecle M, Booy F, Brahimi-Horn MC, Coutelle C, Lemoine NR, Alton EWFW, Miller AD (2002) Characterisation of LMD virus-like nanoparticles self-assembled from cationic liposomes, adenovirus core peptide μ (mu) and plasmid DNA. Gene Ther 9(9):564–576Google Scholar
  27. 27.
    Bharali DJ, Khalil M, Gurbuz M, Simone TM, Mousa SA (2009) Nanoparticles and cancer therapy: a concise review with emphasis on dendrimers. Int J Nanomedicine 4:1–7Google Scholar
  28. 28.
    Cho K, Wang X, Nie S, Chen ZG, Shin DM (2008) Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 14(5):1310–1316. doi: 10.1158/1078-0432.CCR-07-1441 Google Scholar
  29. 29.
    Davis ME, Chen ZG, Shin DM (2008) Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7(9):771–782. doi: 10.1038/nrd2614 Google Scholar
  30. 30.
    Farokhzad OC, Langer R (2009) Impact of nanotechnology on drug delivery. ACS Nano 3(1):16–20. doi: 10.1021/nn900002m Google Scholar
  31. 31.
    Lammers T, Hennink WE, Storm G (2008) Tumour-targeted nanomedicines: principles and practice. Br J Cancer 99(3):392–397. doi: 10.1038/sj.bjc.6604483 Google Scholar
  32. 32.
    Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2(12):751–760. doi: 10.1038/nnano.2007.387 Google Scholar
  33. 33.
    Tanaka T, Decuzzi P, Cristofanilli M, Sakamoto JH, Tasciotti E, Robertson FM, Ferrari M (2009) Nanotechnology for breast cancer therapy. Biomed Microdevices 11(1):49–63. doi: 10.1007/s10544-008-9209-0 Google Scholar
  34. 34.
    Youan BB (2008) Impact of nanoscience and nanotechnology on controlled drug delivery. Nanomedicine (Lond) 3(4):401–406. doi: 10.2217/17435889.3.4.401 Google Scholar
  35. 35.
    Byrne JD, Betancourt T, Brannon-Peppas L (2008) Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev 60(15):1615–1626. doi: 10.1016/j.addr.2008.08.005 Google Scholar
  36. 36.
    Zolnik BS, Sadrieh N (2009) Regulatory perspective on the importance of ADME assessment of nanoscale material containing drugs. Adv Drug Deliv Rev 61(6):422–427. doi: 10.1016/j.addr.2009.03.006 Google Scholar
  37. 37.
    Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46(12 Pt 1):6387–6392Google Scholar
  38. 38.
    Kobayashi H, Watanabe R, Choyke PL (2014) Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target? Theranostics 4(1):81–89Google Scholar
  39. 39.
    Thanou M, Duncan R (2003) Polymer-protein and polymer-drug conjugates in cancer therapy. Curr Opin Investig Drugs 4(6):701–709Google Scholar
  40. 40.
    Cohen BE, Bangham AD (1972) Diffusion of small non-electrolytes across liposome membranes. Nature 236(5343):173–174Google Scholar
  41. 41.
    Johnson SM, Bangham AD (1969) Potassium permeability of single compartment liposomes with and without valinomycin. Biochim Biophys Acta 193(1):82–91Google Scholar
  42. 42.
    Lasic D (ed) (1998) Medical applications of liposomes. Elsevier, AmsterdaamGoogle Scholar
  43. 43.
    Lin Q, Chen J, Zhang Z, Zheng G (2014) Lipid-based nanoparticles in the systemic delivery of siRNA. Nanomedicine 9(1):105–120Google Scholar
  44. 44.
    Allen TM, Cullis PR (2004) Drug delivery systems: entering the mainstream. Science 303(5665):1818–1822. doi: 10.1126/science.1095833 Google Scholar
  45. 45.
    Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4(2):145–160. doi: 10.1038/nrd1632 Google Scholar
  46. 46.
    Forssen EA, Tokes ZA (1983) Improved therapeutic benefits of doxorubicin by entrapment in anionic liposomes. Cancer Res 43(2):546–550Google Scholar
  47. 47.
    Treat J, Greenspan A, Forst D, Sanchez JA, Ferrans VJ, Potkul LA, Woolley PV, Rahman A (1990) Antitumor activity of liposome-encapsulated doxorubicin in advanced breast cancer: phase II study. J Natl Cancer Inst 82(21):1706–1710Google Scholar
  48. 48.
    Robert NJ, Vogel CL, Henderson IC, Sparano JA, Moore MR, Silverman P, Overmoyer BA, Shapiro CL, Park JW, Colbern GT, Winer EP, Gabizon AA (2004) The role of the liposomal anthracyclines and other systemic therapies in the management of advanced breast cancer. Semin Oncol 31(6 Suppl 13):106–146Google Scholar
  49. 49.
    Straubinger RM, Lopez NG, Debs RJ, Hong K, Papahadjopoulos D (1988) Liposome-based therapy of human ovarian cancer: parameters determining potency of negatively charged and antibody-targeted liposomes. Cancer Res 48(18):5237–5245Google Scholar
  50. 50.
    Allen TM, Martin FJ (2004) Advantages of liposomal delivery systems for anthracyclines. Semin Oncol 31(6 Suppl 13):5–15Google Scholar
  51. 51.
    Gabizon A, Martin F (1997) Polyethylene glycol-coated (pegylated) liposomal doxorubicin. Rationale for use in solid tumours. Drugs 54(Suppl 4):15–21Google Scholar
  52. 52.
    Gabizon A, Shmeeda H, Barenholz Y (2003) Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies. Clin Pharmacokinet 42(5):419–436Google Scholar
  53. 53.
    Papahadjopoulos D, Allen TM, Gabizon A, Mayhew E, Matthay K, Huang SK, Lee KD, Woodle MC, Lasic DD, Redemann C et al (1991) Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci U S A 88(24):11460–11464Google Scholar
  54. 54.
    Woodle MC, Lasic DD (1992) Sterically stabilized liposomes. Biochim Biophys Acta 1113(2):171–199Google Scholar
  55. 55.
    Damascelli B, Cantu G, Mattavelli F, Tamplenizza P, Bidoli P, Leo E, Dosio F, Cerrotta AM, Di Tolla G, Frigerio LF, Garbagnati F, Lanocita R, Marchiano A, Patelli G, Spreafico C, Ticha V, Vespro V, Zunino F (2001) Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI-007): phase II study of patients with squamous cell carcinoma of the head and neck and anal canal: preliminary evidence of clinical activity. Cancer 92(10):2592–2602Google Scholar
  56. 56.
    Desai N, Trieu V, Yao Z, Louie L, Ci S, Yang A, Tao C, De T, Beals B, Dykes D, Noker P, Yao R, Labao E, Hawkins M, Soon-Shiong P (2006) Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res 12(4):1317–1324. doi: 10.1158/1078-0432.CCR-05-1634 Google Scholar
  57. 57.
    Miele E, Spinelli GP, Miele E, Tomao F, Tomao S (2009) Albumin-bound formulation of paclitaxel (Abraxane ABI-007) in the treatment of breast cancer. Int J Nanomedicine 4:99–105Google Scholar
  58. 58.
    Vogel SM, Minshall RD, Pilipovic M, Tiruppathi C, Malik AB (2001) Albumin uptake and transcytosis in endothelial cells in vivo induced by albumin-binding protein. Am J Physiol Lung Cell Mol Physiol 281(6):L1512–L1522Google Scholar
  59. 59.
    Hawkins MJ, Soon-Shiong P, Desai N (2008) Protein nanoparticles as drug carriers in clinical medicine. Adv Drug Deliv Rev 60(8):876–885. doi: 10.1016/j.addr.2007.08.044 Google Scholar
  60. 60.
    Davis ME (2009) The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic. Mol Pharm 6(3):659–668. doi: 10.1021/mp900015y Google Scholar
  61. 61.
    Aissaoui A, Chami M, Hussein M, Miller AD (2011) Efficient topical delivery of plasmid DNA to lung in vivo mediated by putative triggered, PEGylated pDNA nanoparticles. J Control Release 154:275–284Google Scholar
  62. 62.
    Carmona S, Jorgensen MR, Kolli S, Crowther C, Salazar FH, Marion PL, Fujino M, Natori Y, Thanou M, Arbuthnot P, Miller AD (2009) Controlling HBV replication in vivo by intravenous administration of triggered PEGylated siRNA-nanoparticles. Mol Pharm 6(3):706–717Google Scholar
  63. 63.
    Drake CR, Aissaoui A, Argyros O, Serginson JM, Monnery BD, Thanou M, Steinke JHG, Miller AD (2010) Bioresponsive small molecule polyamines as non-cytotoxic alternative to polyethylenimine. Mol Pharm 7(6):2040–2055Google Scholar
  64. 64.
    Drake CR, Aissaoui A, Argyros O, Thanou M, Steinke JH, Miller AD (2013) Examination of the effect of increasing the number of intra-disulfide amino functional groups on the performance of small molecule cyclic polyamine disulfide vectors. J Control Release 171(1): 81–90. doi: 10.1016/j.jconrel.2013.02.014
  65. 65.
    Kenny GD, Kamaly N, Kalber TL, Brody LP, Sahuri M, Shamsaei E, Miller AD, Bell JD (2011) Novel multifunctional nanoparticle mediates siRNA tumour delivery, visualisation and therapeutic tumour reduction in vivo. J Control Release 149(2):111–116. doi: 10.1016/j.jconrel.2010.09.020
  66. 66.
    Kolli S, Wong SP, Harbottle R, Johnston B, Thanou M, Miller AD (2013) pH-triggered nanoparticle mediated delivery of siRNA to liver cells in vitro and in vivo. Bioconjug Chem 24(3):314–332. doi: 10.1021/bc3004099 Google Scholar
  67. 67.
    Mével M, Kamaly N, Carmona S, Oliver MH, Jorgensen MR, Crowther C, Salazar FH, Marion PL, Fujino M, Natori Y, Thanou M, Arbuthnot P, Yaouanc J-J, Jaffres PA, Miller AD (2010) DODAG; a versatile new cationic lipid that mediates efficient delivery of pDNA and siRNA. J Control Release 143:222–232Google Scholar
  68. 68.
    Andreu A, Fairweather N, Miller AD (2008) Clostridium neurotoxin fragments as potential targeting moieties for liposomal gene delivery to the CNS. Chembiochem 9(2):219–231Google Scholar
  69. 69.
    Chen J, Jorgensen MR, Thanou M, Miller AD (2011) Post-coupling strategy enables true receptor-targeted nanoparticles. J RNAi Gene Silenc Int j RNA Gene Target Res 7:449–455Google Scholar
  70. 70.
    Wang M, Lowik DW, Miller AD, Thanou M (2009) Targeting the urokinase plasminogen activator receptor with synthetic self-assembly nanoparticles. Bioconjug Chem 20(1):32–40Google Scholar
  71. 71.
    Wang M, Miller AD, Thanou M (2013) Effect of surface charge and ligand organization on the specific cell-uptake of uPAR-targeted nanoparticles. J Drug Target 21(7):684–692. doi: 10.3109/1061186X.2013.805336 Google Scholar
  72. 72.
    Drummond DC, Noble CO, Guo Z, Hong K, Park JW, Kirpotin DB (2006) Development of a highly active nanoliposomal irinotecan using a novel intraliposomal stabilization strategy. Cancer Res 66(6):3271–3277. doi: 10.1158/0008-5472.CAN-05-4007 Google Scholar
  73. 73.
    Flexman JA, Yung A, Yapp DT, Ng SS, Kozlowski P (2008) Assessment of vessel size by MRI in an orthotopic model of human pancreatic cancer. Conf Proc IEEE Eng Med Biol Soc 2008:851–854. doi: 10.1109/IEMBS.2008.4649287 Google Scholar
  74. 74.
    Ting G, Chang CH, Wang HE (2009) Cancer nanotargeted radiopharmaceuticals for tumor imaging and therapy. Anticancer Res 29(10):4107–4118Google Scholar
  75. 75.
    Harrington KJ, Mohammadtaghi S, Uster PS, Glass D, Peters AM, Vile RG, Stewart JS (2001) Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. Clin Cancer Res 7(2):243–254Google Scholar
  76. 76.
    Erdogan S (2009) Liposomal nanocarriers for tumor imaging. J Biomed Nanotechnol 5(2):141–150Google Scholar
  77. 77.
    Mulder WJ, Strijkers GJ, van Tilborg GA, Griffioen AW, Nicolay K (2006) Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging. NMR Biomed 19(1):142–164. doi: 10.1002/nbm.1011 Google Scholar
  78. 78.
    Devoisselle JM, Vion-Dury J, Galons JP, Confort-Gouny S, Coustaut D, Canioni P, Cozzone PJ (1988) Entrapment of gadolinium-DTPA in liposomes. Characterization of vesicles by P-31 NMR spectroscopy. Invest Radiol 23(10):719–724Google Scholar
  79. 79.
    Unger E, Fritz T, Shen DK, Wu G (1993) Manganese-based liposomes. Comparative approaches. Invest Radiol 28(10):933–938Google Scholar
  80. 80.
    Kozlowska D, Foran P, MacMahon P, Shelly MJ, Eustace S, O’Kennedy R (2009) Molecular and magnetic resonance imaging: the value of immunoliposomes. Adv Drug Deliv Rev 61(15):1402–1411. doi: 10.1016/j.addr.2009.09.003 Google Scholar
  81. 81.
    Kabalka GW, Davis MA, Buonocore E, Hubner K, Holmberg E, Huang L (1990) Gd-labeled liposomes containing amphipathic agents for magnetic resonance imaging. Invest Radiol 25(Suppl 1):S63–S64Google Scholar
  82. 82.
    van Tilborg GA, Strijkers GJ, Pouget EM, Reutelingsperger CP, Sommerdijk NA, Nicolay K, Mulder WJ (2008) Kinetics of avidin-induced clearance of biotinylated bimodal liposomes for improved MR molecular imaging. Magn Reson Med 60(6):1444–1456. doi: 10.1002/mrm.21780 Google Scholar
  83. 83.
    Kamaly N, Kalber T, Kenny G, Bell J, Jorgensen M, Miller A (2010) A novel bimodal lipidic contrast agent for cellular labelling and tumour MRI. Org Biomol Chem 8(1):201–211. doi: 10.1039/b910561a Google Scholar
  84. 84.
    Kamaly N, Kalber T, Thanou M, Bell JD, Miller AD (2009) Folate receptor targeted bimodal liposomes for tumor magnetic resonance imaging. Bioconjug Chem 20(4):648–655. doi: 10.1021/bc8002259 Google Scholar
  85. 85.
    Kamaly N, Kalber T, Ahmad A, Oliver MH, So PW, Herlihy AH, Bell JD, Jorgensen MR, Miller AD (2008) Bimodal paramagnetic and fluorescent liposomes for cellular and tumor magnetic resonance imaging. Bioconjug Chem 19(1):118–129. doi: 10.1021/bc7001715 Google Scholar
  86. 86.
    Almeida AJ, Souto E (2007) Solid lipid nanoparticles as a drug delivery system for peptides and proteins. Adv Drug Deliv Rev 59(6):478–490. doi: 10.1016/j.addr.2007.04.007 Google Scholar
  87. 87.
    Cavalli R, Caputo O, Carlotti ME, Trotta M, Scarnecchia C, Gasco MR (1997) Sterilization and freeze-drying of drug-free and drug-loaded solid lipid nanoparticles. Int J Pharm 148(1):47–54Google Scholar
  88. 88.
    Muller RH, Mehnert W, Lucks JS (1995) Solid lipid nanoparticles (Sln) – an alternative colloidal carrier system for controlled drug-delivery. Eur J Pharm Biopharm 41(1):62–69Google Scholar
  89. 89.
    Morel S, Terreno E, Ugazio E, Aime S, Gasco MR (1998) NMR relaxometric investigations of solid lipid nanoparticles (SLN) containing gadolinium(III) complexes. Eur J Pharm Biopharm 45(2):157–163Google Scholar
  90. 90.
    Tomalia DA, Uppuluri S, Swanson DR (1999) Dendritic macromolecules: a fourth major class of polymer architecture – new properties driven by architecture. Mater Res Soc Symp Proc 543:289–298Google Scholar
  91. 91.
    Hawker CJ, Frechet JMJ (1990) Preparation of polymers with controlled molecular architecture – a new convergent approach to dendritic macromolecules. J Am Chem Soc 112(21):7638–7647Google Scholar
  92. 92.
    Svenson S, Tomalia DA (2005) Dendrimers in biomedical applications–reflections on the field. Adv Drug Deliv Rev 57(15):2106–2129. doi: 10.1016/j.addr.2005.09.018 Google Scholar
  93. 93.
    Wolinsky JB, Grinstaff MW (2008) Therapeutic and diagnostic applications of dendrimers for cancer treatment. Adv Drug Deliv Rev 60(9):1037–1055. doi: 10.1016/j.addr.2008.02.012 Google Scholar
  94. 94.
    Barth RF, Coderre JA, Vicente MG, Blue TE (2005) Boron neutron capture therapy of cancer: current status and future prospects. Clin Cancer Res 11(11):3987–4002. doi: 10.1158/1078-0432.CCR-05-0035 Google Scholar
  95. 95.
    Wiener EC, Brechbiel MW, Brothers H, Magin RL, Gansow OA, Tomalia DA, Lauterbur PC (1994) Dendrimer-based metal chelates: a new class of magnetic resonance imaging contrast agents. Magn Reson Med 31(1):1–8Google Scholar
  96. 96.
    Harisinghani MG, Saksena MA, Hahn PF, King B, Kim J, Torabi MT, Weissleder R (2006) Ferumoxtran-10-enhanced MR lymphangiography: does contrast-enhanced imaging alone suffice for accurate lymph node characterization? AJR Am J Roentgenol 186(1):144–148. doi: 10.2214/AJR.04.1287 Google Scholar
  97. 97.
    Sharma R, Saini S, Ros PR, Hahn PF, Small WC, de Lange EE, Stillman AE, Edelman RR, Runge VM, Outwater EK, Morris M, Lucas M (1999) Safety profile of ultrasmall superparamagnetic iron oxide ferumoxtran-10: phase II clinical trial data. J Magn Reson Imagin JMRI 9(2):291–294Google Scholar
  98. 98.
    Islam T, Harisinghani MG (2009) Overview of nanoparticle use in cancer imaging. Cancer Biomark Sect A Dis Markers 5(2):61–67. doi: 10.3233/CBM-2009-0578 Google Scholar
  99. 99.
    Yu MK, Jeong YY, Park J, Park S, Kim JW, Min JJ, Kim K, Jon S (2008) Drug-loaded superparamagnetic iron oxide nanoparticles for combined cancer imaging and therapy in vivo. Angew Chem Int Ed Engl 47(29):5362–5365. doi: 10.1002/anie.200800857 Google Scholar
  100. 100.
    Medarova Z, Pham W, Farrar C, Petkova V, Moore A (2007) In vivo imaging of siRNA delivery and silencing in tumors. Nat Med 13(3):372–377. doi: 10.1038/nm1486 Google Scholar
  101. 101.
    Moore A, Medarova Z (2009) Imaging of siRNA delivery and silencing. Methods Mol Biol 487:93–110. doi: 10.1007/978-1-60327-547-7_5 Google Scholar
  102. 102.
    Yingyuad P, Mevel M, Prata C, Furegati S, Kontogiorgis C, Thanou M, Miller AD (2013) Enzyme-triggered PEGylated pDNA-nanoparticles for controlled release of pDNA in tumors. Bioconjug Chem 24(3):343–362. doi: 10.1021/bc300419g Google Scholar
  103. 103.
    Kong G, Anyarambhatla G, Petros WP, Braun RD, Colvin OM, Needham D, Dewhirst MW (2000) Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. Cancer Res 60(24):6950–6957Google Scholar
  104. 104.
    Poon RT, Borys N (2009) Lyso-thermosensitive liposomal doxorubicin: a novel approach to enhance efficacy of thermal ablation of liver cancer. Expert Opin Pharmacother 10(2):333–343. doi: 10.1517/14656560802677874 Google Scholar
  105. 105.
    Needham D, Anyarambhatla G, Kong G, Dewhirst MW (2000) A new temperature-sensitive liposome for use with mild hyperthermia: characterization and testing in a human tumor xenograft model. Cancer Res 60(5):1197–1201Google Scholar
  106. 106.
    Needham D, Dewhirst MW (2001) The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors. Adv Drug Deliv Rev 53(3):285–305Google Scholar
  107. 107.
    Thomas MB, Jaffe D, Choti MM, Belghiti J, Curley S, Fong Y, Gores G, Kerlan R, Merle P, O’Neil B, Poon R, Schwartz L, Tepper J, Yao F, Haller D, Mooney M, Venook A (2010) Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol 28(25):3994–4005. doi: 10.1200/JCO.2010.28.7805 Google Scholar
  108. 108.
    Wood BJ, Poon RT, Locklin JK, Dreher MR, Ng KK, Eugeni M, Seidel G, Dromi S, Neeman Z, Kolf M, Black CD, Prabhakar R, Libutti SK (2012) Phase I study of heat-deployed liposomal doxorubicin during radiofrequency ablation for hepatic malignancies. J Vasc Interv Radiol 23(2):248–255 e247. S1051-0443(11)01427-8 [pii]. doi: 10.1016/j.jvir.2011.10.018
  109. 109.
    de Smet M, Langereis S, van den Bosch S, Grull H (2010) Temperature-sensitive liposomes for doxorubicin delivery under MRI guidance. J Control Release 143(1):120–127. doi: 10.1016/j.jconrel.2009.12.002 Google Scholar
  110. 110.
    Negussie AH, Yarmolenko PS, Partanen A, Ranjan A, Jacobs G, Woods D, Bryant H, Thomasson D, Dewhirst MW, Wood BJ, Dreher MR (2011) Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound. Int J Hyperthermia 27(2):140–155. doi: 10.3109/02656736.2010.528140 Google Scholar
  111. 111.
    Ranjan A, Jacobs GC, Woods DL, Negussie AH, Partanen A, Yarmolenko PS, Gacchina CE, Sharma KV, Frenkel V, Wood BJ, Dreher MR (2012) Image-guided drug delivery with magnetic resonance guided high intensity focused ultrasound and temperature sensitive liposomes in a rabbit Vx2 tumor model. J Control Release 158(3):487–494. doi: 10.1016/j.jconrel.2011.12.011 Google Scholar
  112. 112.
    Partanen A, Yarmolenko PS, Viitala A, Appanaboyina S, Haemmerich D, Ranjan A, Jacobs G, Woods D, Enholm J, Wood BJ, Dreher MR (2012) Mild hyperthermia with magnetic resonance-guided high-intensity focused ultrasound for applications in drug delivery. Int J Hyperthermia 28(4):320–336. doi: 10.3109/02656736.2012.680173 Google Scholar
  113. 113.
    Kamaly N, Miller AD (2010) Paramagnetic liposome nanoparticles for cellular and tumour imaging. Int J Mol Sci 11(4):1759–1776. doi: 10.3390/ijms11041759 Google Scholar
  114. 114.
    Kamaly N, Miller AD, Bell JD (2010) Chemistry of tumour targeted T1 based MRI contrast agents. Curr Top Med Chem 10(12):1158–1183, BSP/ CTMC /E-Pub/-0067-10-11 [pii]Google Scholar
  115. 115.
    Averitt RD, Westcott SL, Halas NJ (1999) Linear optical properties of gold nanoshells. J Opt Soc Am B 16(10):1824–1832Google Scholar
  116. 116.
    Hirsch LR, Stafford RJ, Bankson JA, Sershen SR, Rivera B, Price RE, Hazle JD, Halas NJ, West JL (2003) Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc Natl Acad Sci U S A 100(23):13549–13554. doi: 10.1073/pnas.2232479100 Google Scholar
  117. 117.
    Lassiter JB, Aizpurua J, Hernandez LI, Brandl DW, Romero I, Lal S, Hafner JH, Nordlander P, Halas NJ (2008) Close encounters between two nanoshells. Nano Lett 8(4):1212–1218. doi: 10.1021/nl080271o Google Scholar
  118. 118.
    Leung K (2004) Iron oxide-ferritin nanocages. doi:NBK61993 [bookaccession]Google Scholar
  119. 119.
    von Maltzahn G, Park JH, Agrawal A, Bandaru NK, Das SK, Sailor MJ, Bhatia SN (2009) Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas. Cancer Res 69(9):3892–3900. doi: 10.1158/0008-5472.CAN-08-4242 Google Scholar
  120. 120.
    Bardhan R, Chen W, Bartels M, Perez-Torres C, Botero MF, McAninch RW, Contreras A, Schiff R, Pautler RG, Halas NJ, Joshi A (2010) Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo. Nano Lett. doi: 10.1021/nl102889y Google Scholar
  121. 121.
    Bardhan R, Lal S, Joshi A, Halas NJ (2011) Theranostic nanoshells: from probe design to imaging and treatment of cancer. Acc Chem Res 44(10):936–946. doi: 10.1021/ar200023x Google Scholar
  122. 122.
    Ye L, Yong KT, Liu L, Roy I, Hu R, Zhu J, Cai H, Law WC, Liu J, Wang K, Liu J, Liu Y, Hu Y, Zhang X, Swihart MT, Prasad PN (2012) A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots. Nat Nanotechnol 7(7):453–458. doi: 10.1038/nnano.2012.74 Google Scholar
  123. 123.
    Chen J, Lanza GM, Wickline SA (2010) Quantitative magnetic resonance fluorine imaging: today and tomorrow. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2(4):431–440. doi: 10.1002/wnan.87 Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Institute of Pharmaceutical ScienceKings College LondonLondonUK
  2. 2.GlobalAcorn LtdLondonUK

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