Nano Research

, Volume 7, Issue 12, pp 1719–1730 | Cite as

Harnessing the collective properties of nanoparticle ensembles for cancer theranostics

  • Yi Liu
  • Jun-Jie Yin
  • Zhihong Nie
Research Article


Individual inorganic nanoparticles (NPs) have been widely used in the fields of drug delivery, cancer imaging and therapy. There are still many hurdles that limit the performance of individual NPs for these applications. The utilization of highly ordered NP ensembles opens a door to resolve these problems, as a result of their new or advanced collective properties. The assembled NPs show several advantages over individual NP-based systems, such as improved cell internalization and tumor targeting, enhanced multimodality imaging capability, superior combination therapy arising from synergistic effects, possible complete clearance from the whole body by degradation of assemblies into original small NP building blocks, and so on. In this review, we discuss the potential of utilizing assembled NP ensembles for cancer imaging and treatment by taking plasmonic vesicular assemblies of Au NPs as an example. We first summarize the recent developments in the self-assembly of plasmonic vesicular structures of NPs from amphiphilic polymer-tethered NP building blocks. We further review the utilization of plasmonic vesicles of NPs for cancer imaging (e.g. multi-photon induced luminescence, photothermal, and photoacoustic imaging), and cancer therapy (e.g., photothermal therapy, and chemotherapy). Finally, we outline current challenges and our perspectives along this line.


vesicle nanoparticle self-assembly cancer theranostics 


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  1. [1]
    Wiedmann, T.; Sadhukha, T.; Hammer, B.; Panyam, J. Image-guided drug delivery in lung cancer. Drug Deliv. Transl. Res. 2012, 2, 31–44.CrossRefGoogle Scholar
  2. [2]
    Mitsudomi, T.; Suda, K.; Yatabe, Y. Surgery for NSCLC in the era of personalized medicine. Nat. Rev. Clin. Oncol. 2013, 10, 235–244.CrossRefGoogle Scholar
  3. [3]
    Devarakonda, S.; Morgensztern, D.; Govindan, R. Molecularly targeted therapies in locally advanced non-small-cell lung cancer. Clin. Lung Cancer 2013, 14, 467–472.CrossRefGoogle Scholar
  4. [4]
    Govindan, R.; Bogart, J.; Vokes, E. E. Locally advanced non-small cell lung cancer: The past, present, and future. J. Thorac. Oncol. 2008, 3, 917–928.CrossRefGoogle Scholar
  5. [5]
    Dean, M.; Fojo, T.; Bates, S. Tumour stem cells and drug resistance. Nat. Rev. Cancer 2005, 5, 275–284.CrossRefGoogle Scholar
  6. [6]
    Sukumar, U.; Bhushan, B.; Dubey, P.; Matai, I.; Sachdev, A.; Packirisamy, G. Emerging applications of nanoparticles for lung cancer diagnosis and therapy. Int. Nano Lett. 2013, 3, 1–17.CrossRefGoogle Scholar
  7. [7]
    Janib, S. M.; Moses, A. S.; MacKay, J. A. Imaging and drug delivery using theranostic nanoparticles. Adv. Drug Delivery Rev. 2010, 62, 1052–1063.CrossRefGoogle Scholar
  8. [8]
    Chan, W. C. W.; Nie, S. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 1998, 281, 2016–2018.CrossRefGoogle Scholar
  9. [9]
    Larson, D. R.; Zipfel, W. R.; Williams, R. M.; Clark, S. W.; Bruchez, M. P.; Wise, F. W.; Webb, W. W. Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 2003, 300, 1434–1436.CrossRefGoogle Scholar
  10. [10]
    Michalet, X.; Pinaud, F. F.; Bentolila, L. A.; Tsay, J. M.; Doose, S.; Li, J. J.; Sundaresan, G.; Wu, A. M.; Gambhir, S. S.; Weiss, S. Quantum dots for live cells, in vivo imaging, and diagnostics. Science 2005, 307, 538–544.CrossRefGoogle Scholar
  11. [11]
    Chen, J. Y.; Yang, M. X.; Zhang, Q. A.; Cho, E. C.; Cobley, C. M.; Kim, C.; Glaus, C.; Wang, L. H. V.; Welch, M. J.; Xia, Y. N. Gold nanocages: A novel class of multifunctional nanomaterials for theranostic applications. Adv. Funct. Mater. 2010, 20, 3684–3694.CrossRefGoogle Scholar
  12. [12]
    Kennedy, L. C.; Bickford, L. R.; Lewinski, N. A.; Coughlin, A. J.; Hu, Y.; Day, E. S.; West, J. L.; Drezek, R. A. A new era for cancer treatment: Gold-nanoparticle-mediated thermal therapies. Small 2011, 7, 169–183.CrossRefGoogle Scholar
  13. [13]
    Dreaden, E. C.; Alkilany, A. M.; Huang, X. H.; Murphy, C. J.; El-Sayed, M. A. The golden age: Gold nanoparticles for biomedicine. Chem. Soc. Rev. 2012, 41, 2740–2779.CrossRefGoogle Scholar
  14. [14]
    Wang, Y. C.; Black, K. C. L.; Luehmann, H.; Li, W. Y.; Zhang, Y.; Cai, X.; Wan, D. H.; Liu, S. Y.; Li, M.; Kim, P.; et al. A. Comparison study of gold nanohexapods, nanorods, and nanocages for photothermal cancer treatment. ACS Nano 2013, 7, 2068–2077.CrossRefGoogle Scholar
  15. [15]
    Khlebtsov, N.; Dykman, L. Biodistribution and toxicity of engineered gold nanoparticles: A review of in vitro and in vivo studies. Chem. Soc. Rev. 2011, 40, 1647–1671.CrossRefGoogle Scholar
  16. [16]
    Nie, Z.; Petukhova, A.; Kumacheva, E. Properties and emerging applications of self-assembled structures made from inorganic nanoparticles. Nat. Nanotechnol. 2010, 5, 15–25.CrossRefGoogle Scholar
  17. [17]
    Jones, M. R.; Osberg, K. D.; Macfarlane, R. J.; Langille, M. R.; Mirkin, C. A. Templated techniques for the synthesis and assembly of plasmonic nanostructures. Chem. Rev. 2011, 111, 3736–3827.CrossRefGoogle Scholar
  18. [18]
    Glotzer, S. C.; Solomon, M. J. Anisotropy of building blocks and their assembly into complex structures. Nat. Mater. 2007, 6, 557–562.CrossRefGoogle Scholar
  19. [19]
    Bai, F.; Wang, D.; Huo, Z.; Chen, W.; Liu, L.; Liang, X.; Chen, C.; Wang, X.; Peng, Q.; Li, Y. A versatile bottom-up assembly approach to colloidal spheres from nanocrystals. Angew. Chem. Int. Ed. 2007, 46, 6650–6653.CrossRefGoogle Scholar
  20. [20]
    Zhuang, J.; Wu, H.; Yang, Y.; Cao, Y. C. Supercrystalline colloidal particles from artificial atoms. J. Am. Chem. Soc. 2007, 129, 14166–14167.CrossRefGoogle Scholar
  21. [21]
    Wang, L. B.; Xu, L. G.; Kuang, H.; Xu, C. L.; Kotov, N. A. Dynamic nanoparticle assemblies. Acc. Chem. Res. 2012, 45, 1916–1926.CrossRefGoogle Scholar
  22. [22]
    Gong, J.; Li, G.; Tang, Z. Self-assembly of noble metal nanocrystals: Fabrication, optical property, and application. Nano Today 2012, 7, 564–585.CrossRefGoogle Scholar
  23. [23]
    Hao, X.; Shang, X.; Wu, J.; Shan, Y.; Cai, M.; Jiang, J.; Huang, Z.; Tang, Z.; Wang, H. Single-particle tracking of hepatitis B virus-like vesicle entry into cells. Small 2011, 7, 1212–1218.CrossRefGoogle Scholar
  24. [24]
    Lin, J.; Wang, S.; Huang, P.; Wang, Z.; Chen, S.; Niu, G.; Li, W.; He, J.; Cui, D.; Lu, G.; et al. Photosensitizer-loaded gold vesicles with strong plasmonic coupling effect for imaging-guided photothermal/photodynamic therapy. ACS Nano 2013, 7, 5320–5329.CrossRefGoogle Scholar
  25. [25]
    He, J.; Huang, X.; Li, Y.-C.; Liu, Y.; Babu, T.; Aronova, M. A.; Wang, S.; Lu, Z.; Chen, X.; Nie, Z. Self-assembly of amphiphilic plasmonic micelle-like nanoparticles in selective solvents. J. Am. Chem. Soc. 2013, 135, 7974–7984.CrossRefGoogle Scholar
  26. [26]
    He, J.; Liu, Y.; Babu, T.; Wei, Z.; Nie, Z. Self-assembly of inorganic nanoparticle vesicles and tubules driven by tethered linear block copolymers. J. Am. Chem. Soc. 2012, 134, 11342–11345.CrossRefGoogle Scholar
  27. [27]
    He, J.; Wei, Z.; Wang, L.; Tomova, Z.; Babu, T.; Wang, C.; Han, X.; Fourkas, J. T.; Nie, Z. Hydrodynamically driven self-assembly of giant vesicles of metal nanoparticles for remote-controlled release. Angew. Chem. Int. Ed. 2013, 52, 2463–2468.CrossRefGoogle Scholar
  28. [28]
    Chou, L. Y. T.; Zagorovsky, K.; Chan, W. C. W. DNA assembly of nanoparticle superstructures for controlled biological delivery and elimination. Nat. Nanotechnol. 2014, 9, 148–155.CrossRefGoogle Scholar
  29. [29]
    Huang, P.; Lin, J.; Li, W.; Rong, P.; Wang, Z.; Wang, S.; Wang, X.; Sun, X.; Aronova, M.; Niu, G.; et al. Biodegradable gold nanovesicles with an ultrastrong plasmonic coupling effect for photoacoustic imaging and photothermal therapy. Angew. Chem. Int. Ed. 2013, 52, 13958–13964.CrossRefGoogle Scholar
  30. [30]
    Guo, X.; Szoka, F. C. Chemical approaches to triggerable lipid vesicles for drug and gene delivery. Acc. Chem. Res. 2003, 36, 335–341.CrossRefGoogle Scholar
  31. [31]
    Sawant, R. R.; Torchilin, V. P. Liposomes as “smart” pharmaceutical nanocarriers. Soft Matter 2010, 6, 4026–4044.CrossRefGoogle Scholar
  32. [32]
    Percec, V.; Wilson, D. A.; Leowanawat, P.; Wilson, C. J.; Hughes, A. D.; Kaucher, M. S.; Hammer, D. A.; Levine, D. H.; Lim, A. J.; Bates, F. S.; et al. Self-assembly of Janus dendrimers into uniform dendrimersomes and other complex architectures. Science 2010, 328, 1009–1014.CrossRefGoogle Scholar
  33. [33]
    Zhang, X.; Rehm, S.; Safont-Sempere, M. M.; Würthner, F. Vesicular perylene dye nanocapsules as supramolecular fluorescent pH sensor systems. Nat. Chem. 2009, 1, 623–629.CrossRefGoogle Scholar
  34. [34]
    Discher, B. M.; Won, Y. Y.; Ege, D. S.; Lee, J. C. M.; Bates, F. S.; Discher, D. E.; Hammer, D. A. Polymersomes: Tough vesicles made from diblock copolymers. Science 1999, 284, 1143–1146.CrossRefGoogle Scholar
  35. [35]
    Huang, H. Y.; Remsen, E. E.; Kowalewski, T.; Wooley, K. L. Nanocages derived from shell cross-linked micelle templates. J. Am. Chem. Soc. 1999, 121, 3805–3806.CrossRefGoogle Scholar
  36. [36]
    Nie, Z.; Fave, D.; Kumacheva E.; Zou, S.; Walker, G. C.; Rubinstein, M. Self-assembly of metal-polymer analogues of amphiphilic triblock copolymers. Nat. Mater. 2007, 6, 609–614.CrossRefGoogle Scholar
  37. [37]
    Nikolic, M. S.; Olsson, C.; Salcher, A.; Kornowski, A.; Rank, A.; Schubert, R.; Frömsdorf, A.; Weller, H.; Förster, S. Micelle and vesicle formation of amphiphilic nanoparticles. Angew. Chem. Int. Ed. 2009, 48, 2752–2754.CrossRefGoogle Scholar
  38. [38]
    Zubarev, E. R.; Xu, J.; Sayyad, A.; Gibson, J. D. Amphiphilicity-driven organization of nanoparticles into discrete assemblies. J. Am. Chem. Soc. 2006, 128, 15098–15099.CrossRefGoogle Scholar
  39. [39]
    Hu, J.; Wu, T.; Zhang, G.; Liu, S. Efficient synthesis of single gold nanoparticle hybrid amphiphilic triblock copolymers and their controlled self-assembly. J. Am. Chem. Soc. 2012, 134, 7624–7627.CrossRefGoogle Scholar
  40. [40]
    Song, J.; Cheng, L.; Liu, A.; Yin, J.; Kuang, M.; Duan, H. Plasmonic vesicles of amphiphilic gold nanocrystals self-assembly and external-stimuli-triggered destruction. J. Am. Chem. Soc. 2011, 133, 10760–10763.CrossRefGoogle Scholar
  41. [41]
    Guo, Y.; Harirchian-Saei, S.; Izumi, C. M. S.; Moffitt, M. G. Block copolymer mimetic self-assembly of inorganic nanoparticles. ACS Nano 2011, 5, 3309–3318.CrossRefGoogle Scholar
  42. [42]
    Wang, B.; Li, B.; Dong, B.; Zhao, B.; Li, C. Y. Homo- and hetero-particle clusters formed by Janus nanoparticles with bicompartment polymer brushes. Macromolecules 2010, 43, 9234–9238.CrossRefGoogle Scholar
  43. [43]
    Andala, D. M.; Shin, S. H. R.; Lee, H.-Y. Bishop, K. J. M. Templated synthesis of amphiphilic nanoparticles at the liquid-liquid interface. ACS Nano 2012, 6, 1044–1050.CrossRefGoogle Scholar
  44. [44]
    Wei, K.; Li, J.; Liu, J.; Chen, G.; Jiang, M. Reversible vesicles of supramolecular hybrid nanoparticles. Soft Matter 2012, 8, 3300–3303.CrossRefGoogle Scholar
  45. [45]
    Liu, Y.; Li, Y.; He, J.; Duelge, K. J.; Lu, Z.; Nie, Z. Entropy-driven pattern formation of hybrid vesicular assemblies made from molecular and nanoparticle amphiphiles. J. Am. Chem. Soc. 2014, 136, 2602–2610.CrossRefGoogle Scholar
  46. [46]
    Song, J.; Zhou, J.; Duan, H. Self-assembled plasmonic vesicles of SERS-encoded amphiphilic gold nanoparticles for cancer cell targeting and traceable intracellular drug delivery. J. Am. Chem. Soc. 2012, 134, 13458–13469.CrossRefGoogle Scholar
  47. [47]
    Niikura, K.; Iyo, N.; Higuchi, T.; Nishio, T.; Jinnai, H.; Fujitani, N.; Ijiro, K. Gold nanoparticles coated with semi-fluorinated oligo(ethylene glycol) produce sub-100 nm nanoparticle vesicles without templates. J. Am. Chem. Soc. 2012, 134, 7632–7635.CrossRefGoogle Scholar
  48. [48]
    Song, J.; Pu, L.; Zhou, J.; Duan, B.; Duan, H. Biodegradable theranostic plasmonic vesicles of amphiphilic gold nanorods. ACS Nano 2013, 7, 9947–9960.CrossRefGoogle Scholar
  49. [49]
    Llevot, A.; Astruc, D. Applications of vectorized gold nanoparticles to the diagnosis and therapy of cancer. Chem. Soc. Rev. 2012, 41, 242–257.CrossRefGoogle Scholar
  50. [50]
    Erathodiyil, N.; Ying, J. Y. Functionalization of inorganic nanoparticles for bioimaging applications. Acc. Chem. Res. 2011, 44, 925–935.CrossRefGoogle Scholar
  51. [51]
    Cheng, Y.; Samia, A. C.; Li, J.; Kenney, M. E.; Resnick, A.; Burda, C. Delivery and efficacy of a cancer drug as a function of the bond to the gold nanoparticle surface. Langmuir 2010, 26, 2248–2255.CrossRefGoogle Scholar
  52. [52]
    Ghosh, P.; Han, G.; De, M.; Kim, C. K.; Rotello, V. M. Gold nanoparticles in delivery applications. Adv. Drug Delivery Rev. 2008, 60, 1307–1315.CrossRefGoogle Scholar
  53. [53]
    He, J.; Zhang, P.; Babu, T.; Liu, Y.; Gong, J.; Nie, Z. Near-infrared light-responsive vesicles of Au nanoflowers. Chem. Commun. 2013, 49, 576–578.CrossRefGoogle Scholar
  54. [54]
    Niikura, K.; Iyo, N.; Matsuo, Y.; Mitomo, H.; Ijiro, K. Sub-100 nm gold nanoparticle vesicles as a drug delivery carrier enabling rapid drug release upon light irradiation. ACS Appl. Mater. Inter. 2013, 5, 3900–3907.CrossRefGoogle Scholar
  55. [55]
    Song, J.; Fang, Z.; Wang, C.; Zhou, J.; Duan, B.; Pu, Lu.; Duan, H. Photolabile plasmonic vesicles assembled from amphiphilic gold nanoparticles for remote-controlled traceable drug delivery. Nanoscale 2013, 5, 5816–5824.CrossRefGoogle Scholar
  56. [56]
    Amstad, E.; Kohlbrecher, J.; Müller, E.; Schweizer, T.; Textor, M.; Reimhult, E. Triggered release from liposomes through magnetic actuation of iron oxide nanoparticle containing membranes. Nano Lett. 2011, 11, 1664–1670.CrossRefGoogle Scholar
  57. [57]
    Gopalakrishnan, G.; Danelon, C.; Izewska, P.; Prummer, M.; Bolinger, P.; Geissbühler, I.; Demurtas, D.; Dubochet, J.; Vogel, H. Multifunctional lipid/quantum dot hybrid nanocontainers for controlled targeting of live cells. Angew. Chem. Int. Ed. 2006, 45, 5478–5483.CrossRefGoogle Scholar
  58. [58]
    Al-Jamal, W. T.; Al-Jamal, K. T.; Tian, B.; Lacerda, L.; Bomans, P. H.; Frederik, P. M.; Kostarelos, K. Lipid-quantum dot bilayer vesicles enhance tumor cell uptake and retention in vitro and in vivo. ACS Nano 2008, 2, 408–418.CrossRefGoogle Scholar
  59. [59]
    Niikura, K.; Iyo, N.; Higuchi, T.; Nishio, T.; Jinnai, H.; Fujitani, N.; Ijiro, K. Gold nanoparticles coated with semi-fluorinated oligo(ethylene glycol) produce sub-100 nm nanoparticle vesicles without templates. J. Am. Chem. Soc. 2012, 134, 7632–7635.CrossRefGoogle Scholar
  60. [60]
    Bian, T.; Shang, L.; Yu, H.; Perez, M. T.; Wu, L.-Z.; Tung, C.-H.; Nie, Z.; Tang, Z.; Zhang, T. Spontaneous organization of inorganic nanoparticles into nanovesicles triggered by UV light. Adv. Mater. 2014, in press, DOI: 10.1002/adma.201401182.Google Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of Chemistry and BiochemistryUniversity of MarylandCollege ParkUSA
  2. 2.Center for Food Safety and Applied NutritionU.S. Food and Drug AdministrationCollege ParkUSA

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