Remotely Triggered Nanotheranostics

  • Abdul K. Parchur
  • Jaidip M. Jagtap
  • Gayatri Sharma
  • Venkateswara Gogineni
  • Sarah B. WhiteEmail author
  • Amit JoshiEmail author
Part of the Bioanalysis book series (BIOANALYSIS, volume 5)


The emerging field of nanotheranostics refers to tens to hundreds of nanometer size constructs that combine diagnostic and therapeutic agents. The favorable and tunable bio-distribution of nanotheranostic agents to disease site can enable seamless image-guided therapies and achieve spatial control of drug delivery. Remotely triggered nanotheranostics with specific material composition build upon these emerging nanomedicine agents to enable external field directed drug release or tumor ablation, thereby achieving complete spatiotemporal control of therapeutic action. In recent years, a multitude of external field-triggered nanotheranostic agents have been proposed for the imaging and treatment of cancer. In this chapter, we provide a concise review of nanotheranostics triggered by electromagnetic, ultrasonic, or thermal fields, including their progress from preclinical validation of clinical trials and the challenges and outlook for remotely triggered nanomedicine. A survey of the literature covered in the chapter indicates extensive progress in preclinical validation and exceptional efficacy of solid tumor-directed nanotheranostics, especially with thermal or photochemically ablative modalities. Clinical studies are currently limited to hyperthermia-based chemotherapy release from nanocarriers, but with increased interest and investments, translation of a wide gamut of remotely triggered nanotheranostics is feasible.


Ablation Biodistribution Cancer therapy Chemotherapy Clinical trials Contrast agents Drug delivery Drug release Fluorescence Gold nanorods Hyperthermia Imaging Image guided Liposomes Magnetic nanoparticles Microwave Nanoparticles Nanotheranostics Photodynamic therapy Photothermal therapy Plasmonic Radiation Remotely triggered Theranostic Ultrasound Uptake 


  1. 1.
    American Cancer Society: Cancer Facts & Figures 2016. American Cancer Society, Atlanta (2016)Google Scholar
  2. 2.
    Clark, A.J., Wiley, D.T., Zuckerman, J.E., Webster, P., Chao, J., Lin, J., Yen, Y., Davis, M.E.: CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing. Proc. Natl. Acad. Sci. U. S. A. 113(14), 3850–3854 (2016). Scholar
  3. 3.
    Apply nanotech to up industrial, agri output. The Daily Star (Bangladesh), April 17, 2012Google Scholar
  4. 4.
    Cuenca, A.G., Jiang, H., Hochwald, S.N., Delano, M., Cance, W.G., Grobmyer, S.R.: Emerging implications of nanotechnology on cancer diagnostics and therapeutics. Cancer. 107(3), 459–466 (2006). Scholar
  5. 5.
    Siegel, R.L., Miller, K.D., Jemal, A.: Cancer statistics, 2016. CA Cancer J. Clin. 66(1), 7–30 (2016). Scholar
  6. 6.
    Miller, S.M., Wang, A.Z.: Nanomedicine in chemoradiation. Ther. Deliv. 4(2), 239–250 (2013). Scholar
  7. 7.
    American Cancer Society: Cancer Treatment & Survivorship Facts & Figures 2016–2017. American Cancer Society, Atlanta (2016)Google Scholar
  8. 8.
    Nanomaterials in Theranostics: Global Markets. PR Newswire, New York (2013)Google Scholar
  9. 9.
    Albanese, A., Tang, P.S., Chan, W.C.: The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu. Rev. Biomed. Eng. 14, 1–16 (2012). Scholar
  10. 10.
    Muhanna, N., Jin, C.S., Huynh, E., Chan, H., Qiu, Y., Jiang, W., Cui, L., Burgess, L., Akens, M.K., Chen, J., Irish, J.C., Zheng, G.: Phototheranostic porphyrin nanoparticles enable visualization and targeted treatment of head and neck cancer in clinically relevant models. Theranostics. 5(12), 1428–1443 (2015). Scholar
  11. 11.
    Caldorera-Moore, M., Guimard, N., Shi, L., Roy, K.: Designer nanoparticles: incorporating size, shape and triggered release into nanoscale drug carriers. Expert Opin. Drug Deliv. 7(4), 479–495 (2010). Scholar
  12. 12.
    Alexandra, S., Derek, V., Paliwal, S., Prakash, R.: Remotely triggered nano-theranostics for cancer applications. Nano. 2017(1), 1–22 (2016). Scholar
  13. 13.
    Sakdinawat, A., Attwood, D.: Nanoscale X-ray imaging. Nat. Photonics. 4(12), 840–848 (2010). Scholar
  14. 14.
    Cui, S., Yin, D., Chen, Y., Di, Y., Chen, H., Ma, Y., Achilefu, S., Gu, Y.: In vivo targeted deep-tissue photodynamic therapy based on near-infrared light triggered upconversion nanoconstruct. ACS Nano. 7(1), 676–688 (2013). Scholar
  15. 15.
    Urban, C., Urban, A.S., Charron, H., Joshi, A.: Externally modulated theranostic nanoparticles. Transl. Cancer. Res. 2(4), 292–308 (2013). Scholar
  16. 16.
    Liu, K., Xue, X., Furlani, E.P.: Theoretical comparison of optical properties of near-infrared colloidal plasmonic nanoparticles. Sci. Rep. 6, 34189 (2016). Scholar
  17. 17.
    Martin, K.H., Dayton, P.A.: Current status and prospects for microbubbles in ultrasound theranostics. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 5(4), 329–345 (2013). Scholar
  18. 18.
    Stern, J.M., Cadeddu, J.A.: Emerging use of nanoparticles for the therapeutic ablation of urologic malignancies. Urol. Oncol. 26(1), 93–96 (2008). Scholar
  19. 19.
    Hayashi, K., Nakamura, M., Miki, H., Ozaki, S., Abe, M., Matsumoto, T., Sakamoto, W., Yogo, T., Ishimura, K.: Magnetically responsive smart nanoparticles for cancer treatment with a combination of magnetic hyperthermia and remote-control drug release. Theranostics. 4(8), 834–844 (2014). Scholar
  20. 20.
    Starkewolf, Z.B., Miyachi, L., Wong, J., Guo, T.: X-ray triggered release of doxorubicin from nanoparticle drug carriers for cancer therapy. Chem. Commun. (Camb.). 49(25), 2545–2547 (2013). Scholar
  21. 21.
    Kascakova, S., Giuliani, A., Lacerda, S., Pallier, A., Mercere, P., Toth, E., Refregiers, M.: X-ray-induced radiophotodynamic therapy (RPDT) using lanthanide micelles: Beyond depth limitations. Nano Res. 8(7), 2373–2379 (2015). Scholar
  22. 22.
    Akamatsu, K.: Development of ‘leaky’ liposome triggered by radiation applicable to a drug reservoir and a simple radiation dosimeter. Appl. Radiat. Isot. 74, 144–151 (2013). Scholar
  23. 23.
    Ayala-Orozco, C., Urban, C., Knight, M.W., Urban, A.S., Neumann, O., Bishnoi, S.W., Mukherjee, S., Goodman, A.M., Charron, H., Mitchell, T., Shea, M., Roy, R., Nanda, S., Schiff, R., Halas, N.J., Joshi, A.: Au nanomatryoshkas as efficient near-infrared photothermal transducers for cancer treatment: benchmarking against nanoshells. ACS Nano. 8(6), 6372–6381 (2014). Scholar
  24. 24.
    Rengan, A.K., Bukhari, A.B., Pradhan, A., Malhotra, R., Banerjee, R., Srivastava, R., De, A.: In vivo analysis of biodegradable liposome gold nanoparticles as efficient agents for photothermal therapy of cancer. Nano Lett. 15(2), 842–848 (2015). Scholar
  25. 25.
    Kuo, C.Y., Liu, T.Y., Chan, T.Y., Tsai, S.C., Hardiansyah, A., Huang, L.Y., Yang, M.C., Lu, R.H., Jiang, J.K., Yang, C.Y., Lin, C.H., Chiu, W.Y.: Magnetically triggered nanovehicles for controlled drug release as a colorectal cancer therapy. Colloids Surf. B Biointerfaces. 140, 567–573 (2016). Scholar
  26. 26.
    Xiao, Q., Zheng, X., Bu, W., Ge, W., Zhang, S., Chen, F., Xing, H., Ren, Q., Fan, W., Zhao, K., Hua, Y., Shi, J.: A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy. J. Am. Chem. Soc. 135(35), 13041–13048 (2013). Scholar
  27. 27.
    Sine, J., Urban, C., Thayer, D., Charron, H., Valim, N., Tata, D.B., Schiff, R., Blumenthal, R., Joshi, A., Puri, A.: Photo activation of HPPH encapsulated in “Pocket” liposomes triggers multiple drug release and tumor cell killing in mouse breast cancer xenografts. Int. J. Nanomedicine. 10, 125–145 (2015). Scholar
  28. 28.
    Han, R., Yi, H., Shi, J., Liu, Z., Wang, H., Hou, Y., Wang, Y.: pH-Responsive drug release and NIR-triggered singlet oxygen generation based on a multifunctional core-shell-shell structure. Phys. Chem. Chem. Phys. 18(36), 25497–25503 (2016). Scholar
  29. 29.
    Zhang, D., Qi, G.B., Zhao, Y.X., Qiao, S.L., Yang, C., Wang, H.: In situ formation of nanofibers from purpurin18-peptide conjugates and the assembly induced retention effect in tumor sites. Adv. Mater. 27(40), 6125–6130 (2015). Scholar
  30. 30.
    Spring, B.Q., Bryan Sears, R., Zheng, L.Z., Mai, Z., Watanabe, R., Sherwood, M.E., Schoenfeld, D.A., Pogue, B.W., Pereira, S.P., Villa, E., Hasan, T.: A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways. Nat. Nanotechnol. 11(4), 378–387 (2016). Scholar
  31. 31.
    Carter, K.A., Shao, S., Hoopes, M.I., Luo, D., Ahsan, B., Grigoryants, V.M., Song, W., Huang, H., Zhang, G., Pandey, R.K., Geng, J., Pfeifer, B.A., Scholes, C.P., Ortega, J., Karttunen, M., Lovell, J.F.: Porphyrin-phospholipid liposomes permeabilized by near-infrared light. Nat. Commun. 5, 3546 (2014). Scholar
  32. 32.
    Chen, Q., Liang, C., Wang, C., Liu, Z.: An imagable and photothermal “Abraxane-like” nanodrug for combination cancer therapy to treat subcutaneous and metastatic breast tumors. Adv. Mater. 27(5), 903–910 (2015). Scholar
  33. 33.
    Peng, H., Cui, B., Zhao, W., Wang, Y., Chang, Z.: Glycine-functionalized Fe3O4@TiO2:Er(3+),Yb(3+) nanocarrier for microwave-triggered controllable drug release and study on mechanism of loading/release process using microcalorimetry. Expert Opin. Drug Deliv. 12(9), 1397–1409 (2015). Scholar
  34. 34.
    Long, D., Liu, T.L., Tan, L.F., Shi, H.T., Liang, P., Tang, S.S., Wu, Q., Yu, J., Dou, J.P., Meng, X.W.: Multisynergistic platform for tumor therapy by mild microwave irradiation-activated chemotherapy and enhanced ablation. ACS Nano. 10(10), 9516–9528 (2016). Scholar
  35. 35.
    Oliveira, H., Perez-Andres, E., Thevenot, J., Sandre, O., Berra, E., Lecommandoux, S.: Magnetic field triggered drug release from polymersomes for cancer therapeutics. J. Control. Release. 169(3), 165–170 (2013). Scholar
  36. 36.
    Derfus, A.M., von Maltzahn, G., Harris, T.J., Duza, T., Vecchio, K.S., Ruoslahti, E., Bhatia, S.N.: Remotely triggered release from magnetic nanoparticles. Adv. Mater. 19(22), 3932–3936 (2007). Scholar
  37. 37.
    Hayashi, K., Ono, K., Suzuki, H., Sawada, M., Moriya, M., Sakamoto, W., Yogo, T.: High-frequency, magnetic-field-responsive drug release from magnetic nanoparticle/organic hybrid based on hyperthermic effect. ACS Appl. Mater. Interfaces. 2(7), 1903–1911 (2010). Scholar
  38. 38.
    Shen, S., Wang, S., Zheng, R., Zhu, X., Jiang, X., Fu, D., Yang, W.: Magnetic nanoparticle clusters for photothermal therapy with near-infrared irradiation. Biomaterials. 39, 67–74 (2015). Scholar
  39. 39.
    Wang, L., Zhang, P., Shi, J., Hao, Y., Meng, D., Zhao, Y., Yanyan, Y., Li, D., Chang, J., Zhang, Z.: Radiofrequency-triggered tumor-targeting delivery system for theranostics application. ACS Appl. Mater. Interfaces. 7(10), 5736–5747 (2015). Scholar
  40. 40.
    Somasundaram, V.H., Pillai, R., Malarvizhi, G., Ashokan, A., Gowd, S., Peethambaran, R., Palaniswamy, S., Unni, A.K.K., Nair, S., Koyakutty, M.: Biodegradable radiofrequency responsive nanoparticles for augmented thermal ablation combined with triggered drug release in liver tumors. ACS Biomater Sci. Eng. 2(5), 768–779 (2016). Scholar
  41. 41.
    Bariana, M., Aw, M.S., Moore, E., Voelcker, N.H., Losic, D.: Radiofrequency-triggered release for on-demand delivery of therapeutics from titania nanotube drug-eluting implants. Nanomedicine (Lond.). 9(8), 1263–1275 (2014). Scholar
  42. 42.
    Griffete, N., Fresnais, J., Espinosa, A., Wilhelm, C., Bee, A., Menager, C.: Design of magnetic molecularly imprinted polymer nanoparticles for controlled release of doxorubicin under an alternative magnetic field in athermal conditions. Nanoscale. 7(45), 18891–18896 (2015). Scholar
  43. 43.
    Kong, G., Anyarambhatla, G., Petros, W.P., Braun, R.D., Colvin, O.M., Needham, D., Dewhirst, M.W.: Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. Cancer Res. 60(24), 6950–6957 (2000)Google Scholar
  44. 44.
    Shirakura, T., Kelson, T.J., Ray, A., Malyarenko, A.E., Kopelman, R.: Hydrogel nanoparticles with thermally controlled drug release. ACS Macro Lett. 3(7), 602–606 (2014). Scholar
  45. 45.
    Manzoor, A.A., Lindner, L.H., Landon, C.D., Park, J.Y., Simnick, A.J., Dreher, M.R., Das, S., Hanna, G., Park, W., Chilkoti, A., Koning, G.A., ten Hagen, T.L., Needham, D., Dewhirst, M.W.: Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors. Cancer Res. 72(21), 5566–5575 (2012). Scholar
  46. 46.
    Paris, J.L., Cabanas, M.V., Manzano, M., Vallet-Regi, M.: Polymer-grafted mesoporous silica nanoparticles as ultrasound-responsive drug carriers. ACS Nano. 9(11), 11023–11033 (2015). Scholar
  47. 47.
    Zhang, K., Xu, H., Jia, X., Chen, Y., Ma, M., Sun, L., Chen, H.: Ultrasound-triggered nitric oxide release platform based on energy transformation for targeted inhibition of pancreatic tumor. ACS Nano. 10(12), 10816–10828 (2016). Scholar
  48. 48.
    Ektate, K., Kapoor, A., Maples, D., Tuysuzoglu, A., VanOsdol, J., Ramasami, S., Ranjan, A.: Motion compensated ultrasound imaging allows thermometry and image guided drug delivery monitoring from echogenic liposomes. Theranostics. 6(11), 1963–1974 (2016). Scholar
  49. 49.
    Antosh, M.P., Wijesinghe, D.D., Shrestha, S., Lanou, R., Huang, Y.H., Hasselbacher, T., Fox, D., Neretti, N., Sun, S., Katenka, N., Cooper, L.N., Andreev, O.A., Reshetnyak, Y.K.: Enhancement of radiation effect on cancer cells by gold-pHLIP. Proc. Natl. Acad. Sci. U. S. A. 112(17), 5372–5376 (2015). Scholar
  50. 50.
    Ghaemi, B., Mashinchian, O., Mousavi, T., Karimi, R., Kharrazi, S., Amani, A.: Harnessing the cancer radiation therapy by lanthanide-doped zinc oxide based theranostic nanoparticles. ACS Appl. Mater. Interfaces. 8(5), 3123–3134 (2016). Scholar
  51. 51.
    Jain, P.K., Lee, K.S., El-Sayed, I.H., El-Sayed, M.A.: Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine. J. Phys. Chem. B. 110, 7238–7248 (2006). Scholar
  52. 52.
    Chen, J., Saeki, F., Wiley, B.J., Cang, H., Cobb, M.J., Li, Z.-Y., Au, L., Zhang, H., Kimmey, M.B., Li, X., Xia, Y.: Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents. Nano Lett. 5, 473–477 (2005). Scholar
  53. 53.
    Radloff, C., Halas, N.J.: Plasmonic properties of concentric nanoshells. Nano Lett. 4, 1323–1327 (2004). Scholar
  54. 54.
    Cole, J., Halas, N.J.: Photothermal efficiencies of nanorods and nanoshells. J. Phys. Chem. C. 113, 12090–12094 (2009)CrossRefGoogle Scholar
  55. 55.
    von Maltzahn, G., Centrone, A., Park, J.H., Ramanathan, R., Sailor, M.J., Hatton, T.A., Bhatia, S.N.: SERS-coded gold nanorods as a multifunctional platform for densely multiplexed near-infrared imaging and photothermal heating. Adv. Mater. 21(31), 3175–3180 (2009). Scholar
  56. 56.
    von Maltzahn, G., Park, J.H., Agrawal, A., Bandaru, N.K., Das, S.K., Sailor, M.J., Bhatia, S.N.: Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas. Cancer Res. 69(9), 3892–3900 (2009). Scholar
  57. 57.
    Bardhan, R., Grady, N.K., Cole, J.R., Joshi, A., Halas, N.J.: Fluorescence enhancement by Au nanostructures: nanoshells and nanorods. ACS Nano. 3(3), 744–752 (2009). Scholar
  58. 58.
    Shi, H., Niu, M., Tan, L., Liu, T., Shao, H., Fu, C., Ren, X., Ma, T., Ren, J., Li, L., Liu, H., Xu, K., Wang, J., Tang, F., Meng, X.: A smart all-in-one theranostic platform for CT imaging guided tumor microwave thermotherapy based on IL@ZrO2 nanoparticles. Chem. Sci. 6(8), 5016–5026 (2015). Scholar
  59. 59.
    Shi, H., Liu, T., Fu, C., Li, L., Tan, L., Wang, J., Ren, X., Ren, J., Meng, X.: Insights into a microwave susceptible agent for minimally invasive microwave tumor thermal therapy. Biomaterials. 44, 91–102 (2015). Scholar
  60. 60.
    Tan, L., Tang, W., Liu, T., Ren, X., Fu, C., Liu, B., Ren, J., Meng, X.: Biocompatible hollow polydopamine nanoparticles loaded ionic liquid enhanced tumor microwave thermal ablation in vivo. ACS Appl. Mater. Interfaces. 8(18), 11237–11245 (2016). Scholar
  61. 61.
    Suseela, S., Urdaneta, M., Wahid, P.: Use of magnetic nanoparticles in microwave ablation. In: Wireless and Microwave Technology Conference (WAMICON), 2015 IEEE 16th Annual, 13–15 April 2015 2015. pp 1–4.
  62. 62.
    Bijukumar, D., Girish, C.M., Sasidharan, A., Nair, S., Koyakutty, M.: Transferrin-conjugated biodegradable graphene for targeted radiofrequency ablation of hepatocellular carcinoma. ACS Biomater Sci. Eng. 1(12), 1211–1219 (2015). Scholar
  63. 63.
    Gobbo, O.L., Sjaastad, K., Radomski, M.W., Volkov, Y., Prina-Mello, A.: Magnetic nanoparticles in cancer theranostics. Theranostics. 5(11), 1249–1263 (2015). Scholar
  64. 64.
    Johnson, N.J.J., Oakden, W., Stanisz, G.J., Scott Prosser, R., van Veggel, F.C.J.M.: Size-tunable, ultrasmall NaGdF4 nanoparticles: insights into their T1 MRI contrast enhancement. Chem. Mater. 23(16), 3714–3722 (2011). Scholar
  65. 65.
    Rotz, M.W., Culver, K.S., Parigi, G., MacRenaris, K.W., Luchinat, C., Odom, T.W., Meade, T.J.: High relaxivity Gd(III)-DNA gold nanostars: investigation of shape effects on proton relaxation. ACS Nano. 9(3), 3385–3396 (2015). Scholar
  66. 66.
    Andrä, W.N., Hannes: Magnetism in Medicine: A Handbook, 1st edn, Wiley-VCH, Berlin (1998)Google Scholar
  67. 67.
    Cherukuri, P., Glazer, E.S., Curley, S.A.: Targeted hyperthermia using metal nanoparticles. Adv. Drug Deliv. Rev. 62(3), 339–345 (2010). Scholar
  68. 68.
    Chen, J., White, S.B., Harris, K.R., Li, W., Yap, J.W., Kim, D.H., Lewandowski, R.J., Shea, L.D., Larson, A.C.: Poly(lactide-co-glycolide) microspheres for MRI-monitored delivery of sorafenib in a rabbit VX2 model. Biomaterials. 61, 299–306 (2015). Scholar
  69. 69.
    Rai, P., Mallidi, S., Zheng, X., Rahmanzadeh, R., Mir, Y., Elrington, S., Khurshid, A., Hasan, T.: Development and applications of photo-triggered theranostic agents. Adv. Drug Deliv. Rev. 62(11), 1094–1124 (2010). Scholar
  70. 70.
    Xing, H., Hwang, K., Lu, Y.: Recent developments of liposomes as nanocarriers for theranostic applications. Theranostics. 6(9), 1336–1352 (2016). Scholar
  71. 71.
    Tashjian, J.A., Dewhirst, M.W., Needham, D., Viglianti, B.L.: Rationale for and measurement of liposomal drug delivery with hyperthermia using non-invasive imaging techniques. Int. J. Hyperth. 24(1), 79–90 (2008). Scholar
  72. 72.
    Song, X., Feng, L., Liang, C., Yang, K., Liu, Z.: Ultrasound triggered tumor oxygenation with oxygen-shuttle nanoperfluorocarbon to overcome hypoxia-associated resistance in cancer therapies. Nano Lett. 16(10), 6145–6153 (2016). Scholar
  73. 73.
    You, D.G., Deepagan, V.G., Um, W., Jeon, S., Son, S., Chang, H., Yoon, H.I., Cho, Y.W., Swierczewska, M., Lee, S., Pomper, M.G., Kwon, I.C., Kim, K., Park, J.H.: ROS-generating TiO2 nanoparticles for non-invasive sonodynamic therapy of cancer. Sci. Rep. 6, 23200 (2016). Scholar
  74. 74.
    Lentacker, I., Geers, B., Demeester, J., De Smedt, S.C., Sanders, N.N.: Tumor cell killing efficiency of doxorubicin loaded microbubbles after ultrasound exposure. J. Control. Release. 148(1), e113–e114 (2010). Scholar
  75. 75.
    Suzuki, R., Namai, E., Oda, Y., Nishiie, N., Otake, S., Koshima, R., Hirata, K., Taira, Y., Utoguchi, N., Negishi, Y., Nakagawa, S., Maruyama, K.: Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure. J. Control. Release. 142(2), 245–250 (2010). Scholar
  76. 76.
    Rapoport, N., Gao, Z., Kennedy, A.: Multifunctional nanoparticles for combining ultrasonic tumor imaging and targeted chemotherapy. J. Natl. Cancer Inst. 99(14), 1095–1106 (2007). Scholar
  77. 77.
    Ferrara, K., Pollard, R., Borden, M.: Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery. Annu. Rev. Biomed. Eng. 9, 415–447 (2007). Scholar
  78. 78.
    Figueiredo, M., Esenaliev, R.: PLGA nanoparticles for ultrasound-mediated gene delivery to solid tumors. J. Drug Del. 2012, 767839 (2012). Scholar
  79. 79.
    Min, H.S., You, D.G., Son, S., Jeon, S., Park, J.H., Lee, S., Kwon, I.C., Kim, K.: Echogenic glycol chitosan nanoparticles for ultrasound-triggered cancer theranostics. Theranostics. 5(12), 1402–1418 (2015). Scholar
  80. 80.
    Taniyama, Y., Azuma, J., Rakugi, H., Morishita, R.: Plasmid DNA-based gene transfer with ultrasound and microbubbles. Curr. Gene Ther. 11(6), 485–490 (2011)CrossRefGoogle Scholar
  81. 81.
    Wong, A.W., Fite, B.Z., Liu, Y., Kheirolomoom, A., Seo, J.W., Watson, K.D., Mahakian, L.M., Tam, S.M., Zhang, H., Foiret, J., Borowsky, A.D., Ferrara, K.W.: Ultrasound ablation enhances drug accumulation and survival in mammary carcinoma models. J. Clin. Invest. 126(1), 99–111 (2016). Scholar
  82. 82.
    Hanahan, D., Weinberg, R.A.: The hallmarks of cancer. Cell. 100(1), 57–70 (2000)CrossRefGoogle Scholar
  83. 83.
    Hanahan, D., Weinberg, R.A.: Hallmarks of cancer: the next generation. Cell. 144(5), 646–674 (2011). Scholar
  84. 84.
    Bisht, S., Maitra, A.: Dextran-doxorubicin/chitosan nanoparticles for solid tumor therapy. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 1(4), 415–425 (2009). Scholar
  85. 85.
    Lammers, T., Kiessling, F., Hennink, W.E., Storm, G.: Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. J. Control. Release. 161(2), 175–187 (2012). Scholar
  86. 86.
    Yan, Y., Li, G.X., Yuan, J.S.: Study on mechanism of eye-signs in blood stasis syndrome. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine/Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban. 16(4), 213–215 (1996)Google Scholar
  87. 87.
    McNeil, S.E.: Nanotechnology for the biologist. J. Leukoc. Biol. 78(3), 585–594 (2005). Scholar
  88. 88.
    Peng, X.H., Qian, X., Mao, H., Wang, A.Y., Chen, Z.G., Nie, S., Shin, D.M.: Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy. Int. J. Nanomedicine. 3(3), 311–321 (2008)Google Scholar
  89. 89.
    Huang, X., Peng, X., Wang, Y., Shin, D.M., El-Sayed, M.A., Nie, S.: A reexamination of active and passive tumor targeting by using rod-shaped gold nanocrystals and covalently conjugated peptide ligands. ACS Nano. 4(10), 5887–5896 (2010). Scholar
  90. 90.
    Nie, S.: Understanding and overcoming major barriers in cancer nanomedicine. Nanomedicine (Lond.). 5(4), 523–528 (2010). Scholar
  91. 91.
    Bartlett, D.W., Su, H., Hildebrandt, I.J., Weber, W.A., Davis, M.E.: Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc. Natl. Acad. Sci. U. S. A. 104(39), 15549–15554 (2007). Scholar
  92. 92.
    Dreher, M.R., Liu, W., Michelich, C.R., Dewhirst, M.W., Yuan, F., Chilkoti, A.: Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J. Natl. Cancer Inst. 98(5), 335–344 (2006). Scholar
  93. 93.
    Mamot, C., Ritschard, R., Wicki, A., Stehle, G., Dieterle, T., Bubendorf, L., Hilker, C., Deuster, S., Herrmann, R., Rochlitz, C.: Tolerability, safety, pharmacokinetics, and efficacy of doxorubicin-loaded anti-EGFR immunoliposomes in advanced solid tumours: a phase 1 dose-escalation study. Lancet Oncol. 13(12), 1234–1241 (2012). Scholar
  94. 94.
    Weiss, G.J., Chao, J., Neidhart, J.D., Ramanathan, R.K., Bassett, D., Neidhart, J.A., Choi, C.H., Chow, W., Chung, V., Forman, S.J., Garmey, E., Hwang, J., Kalinoski, D.L., Koczywas, M., Longmate, J., Melton, R.J., Morgan, R., Oliver, J., Peterkin, J.J., Ryan, J.L., Schluep, T., Synold, T.W., Twardowski, P., Davis, M.E., Yen, Y.: First-in-human phase 1/2a trial of CRLX101, a cyclodextrin-containing polymer-camptothecin nanopharmaceutical in patients with advanced solid tumor malignancies. Investig. New Drugs. 31(4), 986–1000 (2013). Scholar
  95. 95.
    Pillai, G.: Nanomedicines for cancer therapy: an update of FDA approved and those under various stages of development. Pharm. Pharm. Sci. 1(2), 13 (2014)Google Scholar
  96. 96.
    Karimi, M., Ghasemi, A., Sahandi Zangabad, P., Rahighi, R., Moosavi Basri, S.M., Mirshekari, H., Amiri, M., Shafaei Pishabad, Z., Aslani, A., Bozorgomid, M., Ghosh, D., Beyzavi, A., Vaseghi, A., Aref, A.R., Haghani, L., Bahrami, S., Hamblin, M.R.: Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems. Chem. Soc. Rev. 45(5), 1457–1501 (2016). Scholar
  97. 97.
    Stern, J.M., Kibanov Solomonov, V.V., Sazykina, E., Schwartz, J.A., Gad, S.C., Goodrich, G.P.: Initial evaluation of the safety of nanoshell-directed photothermal therapy in the treatment of prostate disease. Int. J. Toxicol. 35(1), 38–46 (2016). Scholar
  98. 98.
    Gad, S.C., Sharp, K.L., Montgomery, C., Payne, J.D., Goodrich, G.P.: Evaluation of the toxicity of intravenous delivery of auroshell particles (gold-silica nanoshells). Int. J. Toxicol. 31(6), 584–594 (2012). Scholar
  99. 99.
    Zagar, T.M., Vujaskovic, Z., Formenti, S., Rugo, H., Muggia, F., O'Connor, B., Myerson, R., Stauffer, P., Hsu, I.C., Diederich, C., Straube, W., Boss, M.K., Boico, A., Craciunescu, O., Maccarini, P., Needham, D., Borys, N., Blackwell, K.L., Dewhirst, M.W.: Two phase I dose-escalation/pharmacokinetics studies of low temperature liposomal doxorubicin (LTLD) and mild local hyperthermia in heavily pretreated patients with local regionally recurrent breast cancer. Int. J. Hyperth. 30(5), 285–294 (2014). Scholar
  100. 100.
    Church, J.W.: Celsion Presents Data on ThermoDox® plus Optimized RFA in Intermediate Primary Liver Cancer at the 3rd Asian Conference on Tumor Ablation (ACTA). Celsion Corporation (2016)Google Scholar
  101. 101.
    Maggiorella, L., Barouch, G., Devaux, C., Pottier, A., Deutsch, E., Bourhis, J., Borghi, E., Levy, L.: Nanoscale radiotherapy with hafnium oxide nanoparticles. Future Oncol. 8(9), 1167–1181 (2012). Scholar
  102. 102.
    Bonvalot, S., Le Pechoux, C., De Baere, T., Buy, X., Italiano, A., Stockle, E., Terrier, P., Lassau, N., Le Cesne, A., Sargos, P., Antoine, M., Lezghed, N., Azzouz, F., Goberna, A., Levy, L., Elsa, B., Dimitriu, M., Soria, J.-C., Deutsch, E.: Phase I study of NBTXR3 nanoparticles, in patients with advanced soft tissue sarcoma (STS). ASCO Meeting Abstracts. 32. (15_suppl, 10563 (2014)Google Scholar
  103. 103.
    Larsen, J.E., Henriksen, J.R., Bæksted, M., Andresen, T.L., Jacobsen, G.K., Jørgensen, K.: Liposome-based drug delivery using secretory phospholipase A2 as a tumor-specific release mechanism: preclinical evaluation of efficacy, pharmacokinetics, and individual patient expression profiles. Clin. Cancer Res. 12(19 Supplement), B24 (2014)Google Scholar
  104. 104.
    Cai, W., Chen, X.: Nanoplatforms for targeted molecular imaging in living subjects. Small. 3(11), 1840–1854 (2007). Scholar
  105. 105.
    Radu, C.G., Shu, C.J., Nair-Gill, E., Shelly, S.M., Barrio, J.R., Satyamurthy, N., Phelps, M.E., Witte, O.N.: Molecular imaging of lymphoid organs and immune activation by positron emission tomography with a new [18F]-labeled 2′-deoxycytidine analog. Nat. Med. 14(7), 783–788 (2008). Scholar
  106. 106.
    Schwarzenberg, J., Radu, C.G., Benz, M., Fueger, B., Tran, A.Q., Phelps, M.E., Witte, O.N., Satyamurthy, N., Czernin, J., Schiepers, C.: Human biodistribution and radiation dosimetry of novel PET probes targeting the deoxyribonucleoside salvage pathway. Eur. J. Nucl. Med. Mol. Imaging. 38(4), 711–721 (2011). Scholar
  107. 107.
    Wang, Y.X.: Superparamagnetic iron oxide based MRI contrast agents: current status of clinical application. Quant. Imaging Med. Surg. 1(1), 35–40 (2011). Scholar
  108. 108.
    Perazella, M.A.: Gadolinium-contrast toxicity in patients with kidney disease: nephrotoxicity and nephrogenic systemic fibrosis. Curr. Drug Saf. 3(1), 67–75 (2008)CrossRefGoogle Scholar
  109. 109.
    Debbage, P., Jaschke, W.: Molecular imaging with nanoparticles: giant roles for dwarf actors. Histochem. Cell Biol. 130(5), 845–875 (2008)CrossRefGoogle Scholar
  110. 110.
    Hahn, M., Singh, A., Sharma, P.: Nanoparticles as contrast agents for in-vivo bioimaging: current status and future perspectives. Anal. Bioanal. Chem. 399(1), 3–27 (2011)CrossRefGoogle Scholar
  111. 111.
    Garner, A., Colin, R.: Less is more: the human microdosing concept. Drug Discov. Today. 10(7), 1359–6446 (2005)CrossRefGoogle Scholar
  112. 112.
    A report from Grand View Research Inc.: Nanomedicine market projected to reach $344 billion by 2024 (2016)Google Scholar

Copyright information

© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019

Authors and Affiliations

  • Abdul K. Parchur
    • 1
  • Jaidip M. Jagtap
    • 1
  • Gayatri Sharma
    • 1
  • Venkateswara Gogineni
    • 1
  • Sarah B. White
    • 1
    Email author
  • Amit Joshi
    • 1
    Email author
  1. 1.Departments of Biomedical Engineering & RadiologyMedical College of WisconsinMilwaukeeUSA

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