Nano Research

, Volume 10, Issue 9, pp 3124–3135 | Cite as

Gram-scale synthesis of nanotherapeutic agents for CT/T1-weighted MRI bimodal imaging guided photothermal therapy

  • Xianguang Ding
  • Xiaoxia Hao
  • Dongdong Fu
  • Mengxin Zhang
  • Tian Lan
  • Chunyan Li
  • Renjun Huang
  • Zhijun Zhang
  • Yonggang Li
  • Qiangbin Wang
  • Jiang Jiang
Research Article

Abstract

Theranostic nanomedicine, which uses both imaging and therapeutic components for simultaneous disease diagnosis and treatment, is expected to improve patient treatment safety and outcomes by offering a more personalized approach to medicine. However, the poor reproducibilities of nanomedicines synthesized for optimized bioavailability and their potential toxicity are impeding clinical development. Moreover, milligram-scale synthetic methods are often inconsistent when transferred to mass production. To address these challenges, a facile, room temperature, aqueous phase synthesis of nanotheranostic agents using clinically validated mesoporous silica and naturally derived polydopamine has been developed. Since the synthetic procedure is simple and robust, and requires only simple mixing under ambient conditions, excellent batch-to-batch consistency has been achieved. As a result, this process can be easily scaled-up to produce gram-scale batches with physicochemical parameters similar to those of materials synthesized in smaller batches. The resulting nanotheranostic agents exhibit efficient X-ray tomography and T1-weighted magnetic resonance image contrast enhancing abilities due to their chemically ligated, benign Bi3+ and Fe3+ ions. Furthermore, the inclusion of a polydopamine shell makes the nanoparticle surface easy to functionalize and renders these materials highly efficient as photothermal agents. These nanotheranostic agents are suitable for mass production and for potential applications in multimodal imaging-guided therapy in clinical settings.

Keywords

mesoporous silica polydopamine theranostic multimodal imaging mass production 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

12274_2017_1530_MOESM1_ESM.pdf (2.7 mb)
Gram-scale synthesis of nanotherapeutic agents for CT/T1-weighted MRI bimodal imaging guided photothermal therapy

References

  1. [1]
    Janib, S. M.; Moses, A. S.; MacKay, J. A. Imaging and drug delivery using theranostic nanoparticles. Adv. Drug Deliv. Rev. 2010, 62, 1052–1063.CrossRefGoogle Scholar
  2. [2]
    MacKay, J. A.; Li, Z. B. Theranostic agents that co-deliver therapeutic and imaging agents? Adv. Drug Deliv. Rev. 2010, 62, 1003–1004.CrossRefGoogle Scholar
  3. [3]
    Chen, X. Y.; Gambhir, S. S.; Cheon, J. Theranostic nanomedicine. Acc. Chem. Res. 2011, 44, 841–841.CrossRefGoogle Scholar
  4. [4]
    Cheng, L.; Yang, K.; Li, Y. G.; Chen, J. H.; Wang, C.; Shao, M. W.; Lee, S.-T.; Liu, Z. Facile preparation of multifunctional upconversion nanoprobes for multimodal imaging and dual-targeted photothermal therapy. Angew. Chem., Int. Ed. 2011, 50, 7385–7390.CrossRefGoogle Scholar
  5. [5]
    Deng, H.; Dai, F. Y.; Ma, G. H.; Zhang, X. Theranostic gold nanomicelles made from biocompatible comb-like polymers for thermochemotherapy and multifunctional imaging with rapid clearance. Adv. Mater. 2015, 27, 3645–3653.CrossRefGoogle Scholar
  6. [6]
    McQuade, C.; Al Zaki, A.; Desai, Y.; Vido, M.; Sakhuja, T.; Cheng, Z. L.; Hickey, R. J.; Joh, D.; Park, S.-J.; Kao, G. et al. A multifunctional nanoplatform for imaging, radiotherapy, and the prediction of therapeutic response. Small 2015, 11, 834–843.CrossRefGoogle Scholar
  7. [7]
    Tian, Q. W.; Hu, J. Q.; Zhu, Y. H.; Zou, R. J.; Chen, Z. G.; Yang, S. P.; Li, R. W.; Su, Q. Q.; Han, Y.; Liu, X. G. Sub-10 nm Fe3O4@Cu2-xS core–shell nanoparticles for dual-modal imaging and photothermal therapy. J. Am. Chem. Soc. 2013, 135, 8571–8577.CrossRefGoogle Scholar
  8. [8]
    Fan, Q. L.; Cheng, K.; Hu, X.; Ma, X. W.; Zhang, R. P.; Yang, M.; Lu, X. M.; Xing, L.; Huang, W.; Gambhir, S. S., et al. Transferring biomarker into molecular probe: Melanin nanoparticle as a naturally active platform for multimodality imaging. J. Am. Chem. Soc. 2014, 136, 15185–15194.CrossRefGoogle Scholar
  9. [9]
    Xiao, Q. F.; Zheng, X. P.; Bu, W. B.; Ge, W. Q.; Zhang, S. J.; Chen, F.; Xing, H. Y.; Ren, Q. G.; Fan, W. P.; Zhao, K. L. et al. A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/ photothermal synergistic therapy. J. Am. Chem. Soc. 2013, 135, 13041–13048.CrossRefGoogle Scholar
  10. [10]
    Wang, Y.; Gu, H. C. Core–shell-type magnetic mesoporous silica nanocomposites for bioimaging and therapeutic agent delivery. Adv. Mater. 2015, 27, 576–585.CrossRefGoogle Scholar
  11. [11]
    Yildirimer, L.; Thanh, N. T. K.; Loizidou, M.; Seifalian, A. M. Toxicology and clinical potential of nanoparticles. Nano Today 2011, 6, 585–607.CrossRefGoogle Scholar
  12. [12]
    Kirsh, R.; Hood, S.; Brook, C.; Gilmartin, A.; Dell’ orco, P.; Meek, T. Will nanomedicine deliver on its promise of changing therapeutics or remain an interesting and important research tool in cell biology and physiology? Int. J. Pharm. 2013, 454, 530–531.Google Scholar
  13. [13]
    Venditto, V. J.; Szoka, F. C. Cancer nanomedicines: So many papers and so few drugs! Adv. Drug Deliv. Rev. 2013, 65, 80–88.CrossRefGoogle Scholar
  14. [14]
    Holzapfel, B. M.; Reichert, J. C.; Schantz, J.-T.; Gbureck, U.; Rackwitz, L.; Nöth, U.; Jakob, F.; Rudert, M.; Groll, J.; Hutmacher, D. W. How smart do biomaterials need to be? A translational science and clinical point of view. Adv. Drug Deliv. Rev. 2013, 65, 581–603.CrossRefGoogle Scholar
  15. [15]
    Bazile, D. V. Nanotechnologies in drug delivery—An industrial perspective. J. Drug Deliv. Sci. Technol. 2014, 24, 12–21.CrossRefGoogle Scholar
  16. [16]
    Min, Y. Z.; Caster, J. M.; Eblan, M. J.; Wang, A. Z. Clinical translation of nanomedicine. Chem. Rev. 2015, 115, 11147–11190.CrossRefGoogle Scholar
  17. [17]
    Wei, A.; Mehtala, J. G.; Patri, A. K. Challenges and opportunities in the advancement of nanomedicines. J. Controlled Release 2012, 164, 236–246.CrossRefGoogle Scholar
  18. [18]
    Marre, S.; Jensen, K. F. Synthesis of micro and nanostructures in microfluidic systems. Chem. Soc. Rev. 2010, 39, 1183–1202.CrossRefGoogle Scholar
  19. [19]
    Valencia, P. M.; Farokhzad, O. C.; Karnik, R.; Langer, R. Microfluidic technologies for accelerating the clinical translation of nanoparticles. Nat. Nanotechnol. 2012, 7, 623–629.CrossRefGoogle Scholar
  20. [20]
    Zhang, L.; Xia, Y. N. Scaling up the production of colloidal nanocrystals: Should we increase or decrease the reaction volume? Adv. Mater. 2014, 26, 2600–2606.Google Scholar
  21. [21]
    Naahidi, S.; Jafari, M.; Edalat, F.; Raymond, K.; Khademhosseini, A.; Chen, P. Biocompatibility of engineered nanoparticles for drug delivery. J. Controlled Release 2013, 166, 182–194.CrossRefGoogle Scholar
  22. [22]
    Winnik, F. M.; Maysinger, D. Quantum dot cytotoxicity and ways to reduce it. Acc. Chem. Res. 2013, 46, 672–680.CrossRefGoogle Scholar
  23. [23]
    Cheng, Z. L.; Al Zaki, A.; Hui, J. Z.; Muzykantov, V. R.; Tsourkas, A. Multifunctional nanoparticles: Cost versus benefit of adding targeting and imaging capabilities. Science 2012, 338, 903–910.CrossRefGoogle Scholar
  24. [24]
    Li, C. A targeted approach to cancer imaging and therapy. Nat. Mater. 2014, 13, 110–115.CrossRefGoogle Scholar
  25. [25]
    Tang, L.; Cheng, J. J. Nonporous silica nanoparticles for nanomedicine application. Nano Today 2013, 8, 290–312.CrossRefGoogle Scholar
  26. [26]
    Yang, P. P.; Gai, S. L.; Lin, J. Functionalized mesoporous silica materials for controlled drug delivery. Chem. Soc. Rev. 2012, 41, 3679–3698.CrossRefGoogle Scholar
  27. [27]
    Slowing, I. I.; Vivero-Escoto, J. L.; Wu, C.-W.; Lin, V. S. Y. Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv. Drug Deliv. Rev. 2008, 60, 1278–1288.CrossRefGoogle Scholar
  28. [28]
    Mamaeva, V.; Sahlgren, C.; Lindén, M. Mesoporous silica nanoparticles in medicine—Recent advances. Adv. Drug Deliv. Rev. 2013, 65, 689–702.CrossRefGoogle Scholar
  29. [29]
    Yang, S.; Chen, D. Y.; Li, N. J.; Xu, Q. F.; Li, H.; Gu, F.; Xie, J. P.; Lu, J. M. Hollow mesoporous silica nanocarriers with multifunctional capping agents for in vivo cancer imaging and therapy. Small 2016, 12, 360–370.CrossRefGoogle Scholar
  30. [30]
    Chiang, Y.-D.; Lian, H.-Y.; Leo, S.-Y.; Wang, S.-G.; Yamauchi, Y.; Wu, K. C. W. Controlling particle size and structural properties of mesoporous silica nanoparticles using the taguchi method. J. Phys. Chem. C 2011, 115, 13158–13165.CrossRefGoogle Scholar
  31. [31]
    Malgras, V.; Ji, Q. M.; Kamachi, Y.; Mori, T.; Shieh, F.-K.; Wu, K. C. W.; Ariga, K.; Yamauchi, Y. Templated synthesis for nanoarchitectured porous materials. Bull. Chem. Soc. Jpn. 2015, 88, 1171–1200.CrossRefGoogle Scholar
  32. [32]
    Wu, K. C. W.; Yamauchi, Y. Controlling physical features of mesoporous silica nanoparticles (MSNs) for emerging applications. J. Mater. Chem. 2012, 22, 1251–1256.CrossRefGoogle Scholar
  33. [33]
    Yang, G. B.; Gong, H.; Qian, X. X.; Tan, P. L.; Li, Z. W.; Liu, T.; Liu, J. J.; Li, Y. Y.; Liu, Z. Mesoporous silica nanorods intrinsically doped with photosensitizers as a multifunctional drug carrier for combination therapy of cancer. Nano Res. 2015, 8, 751–764.CrossRefGoogle Scholar
  34. [34]
    Liu, T.; Wu, G. Y.; Cheng, J. J.; Lu, Q.; Yao, Y. J.; Liu, Z. J.; Zhu, D. C.; Zhou, J.; Xu, J. R.; Zhu, J. et al. Multifunctional lymph-targeted platform based on Mn@mSiO2 nanocomposites: Combining PFOB for dual-mode imaging and DOX for cancer diagnose and treatment. Nano Res. 2016, 9, 473–489.CrossRefGoogle Scholar
  35. [35]
    Chen, Y.; Chen, H. R.; Shi, J. L. In vivo bio-safety evaluations and diagnostic/therapeutic applications of chemically designed mesoporous silica nanoparticles. Adv. Mater. 2013, 25, 3144–3176.CrossRefGoogle Scholar
  36. [36]
    Ambrogio, M. W.; Thomas, C. R.; Zhao, Y.-L.; Zink, J. I.; Stoddart, J. F. Mechanized silica nanoparticles: A new frontier in theranostic nanomedicine. Acc. Chem. Res. 2011, 44, 903–913.CrossRefGoogle Scholar
  37. [37]
    Tang, F. Q.; Li, L. L.; Chen, D. Mesoporous silica nanoparticles: Synthesis, biocompatibility and drug delivery. Adv. Mater. 2012, 24, 1504–1534.CrossRefGoogle Scholar
  38. [38]
    Benezra, M.; Penate-Medina, O.; Zanzonico, P. B.; Schaer, D.; Ow, H.; Burns, A.; DeStanchina, E.; Longo, V.; Herz, E.; Iyer, S. et al. Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma. J. Clin. Invest. 2011, 121, 2768–2780.CrossRefGoogle Scholar
  39. [39]
    Lee, H.; Dellatore, S. M.; Miller, W. M.; Messersmith, P. B. Mussel-inspired surface chemistry for multifunctional coatings. Science 2007, 318, 426–430.CrossRefGoogle Scholar
  40. [40]
    Xu, C. J.; Xu, K. M.; Gu, H. W.; Zheng, R. K.; Liu, H.; Zhang, X. X.; Guo, Z. H.; Xu, B. Dopamine as a robust anchor to immobilize functional molecules on the iron oxide shell of magnetic nanoparticles. J. Am. Chem. Soc. 2004, 126, 9938–9939.CrossRefGoogle Scholar
  41. [41]
    Hong, S.; Kim, K. Y.; Wook, H. J.; Park, S. Y.; Lee, K. D.; Lee, D. Y.; Lee, H. Attenuation of the in vivo toxicity of biomaterials by polydopamine surface modification. Nanomedicine 2011, 6, 793–801.CrossRefGoogle Scholar
  42. [42]
    Lee, H.; Rho, J.; Messersmith, P. B. Facile conjugation of biomolecules onto surfaces via mussel adhesive protein inspired coatings. Adv. Mater. 2009, 21, 431–434.CrossRefGoogle Scholar
  43. [43]
    Ju, K.-Y.; Lee, J. W.; Im, G. H.; Lee, S.; Pyo, J.; Park, S. B.; Lee, J. H.; Lee, J.-K. Bio-inspired, melanin-like nanoparticles as a highly efficient contrast agent for T1-weighted magnetic resonance imaging. Biomacromolecules 2013, 14, 3491–3497.CrossRefGoogle Scholar
  44. [44]
    Miao, Z.-H.; Wang, H.; Yang, H. J.; Li, Z.-L.; Zhen, L.; Xu, C.-Y. Intrinsically Mn2+-chelated polydopamine nanoparticles for simultaneous magnetic resonance imaging and photothermal ablation of cancer cells. ACS Appl. Mater. Interfaces 2015, 7, 16946–16952.CrossRefGoogle Scholar
  45. [45]
    Liu, Y. L.; Ai, K. L.; Liu, J. H.; Deng, M.; He, Y. Y.; Lu, L. H. Dopamine-melanin colloidal nanospheres: An efficient near-infrared photothermal therapeutic agent for in vivo cancer therapy. Adv. Mater. 2013, 25, 1353–1359.CrossRefGoogle Scholar
  46. [46]
    Lin, L.-S.; Cong, Z.-X.; Cao, J.-B.; Ke, K.-M.; Peng, Q.-L.; Gao, J. H.; Yang, H.-H.; Liu, G.; Chen, X. Y. Multifunctional Fe3O4@polydopamine core–shell nanocomposites for intracellular mRNA detection and imaging-guided photothermal therapy. ACS Nano 2014, 8, 3876–3883.CrossRefGoogle Scholar
  47. [47]
    Zheng, Q. S.; Lin, T. R.; Wu, H. Y.; Guo, L. Q.; Ye, P. R.; Hao, Y. L.; Guo, Q. Q.; Jiang, J. Z.; Fu, F. F.; Chen, G. N. Mussel-inspired polydopamine coated mesoporous silica nanoparticles as pH-sensitive nanocarriers for controlled release. Int. J. Pharm. 2014, 463, 22–26.CrossRefGoogle Scholar
  48. [48]
    Chang, D. F.; Gao, Y. F.; Wang, L. J.; Liu, G.; Chen, Y. H.; Wang, T.; Tao, W.; Mei, L.; Huang, L. Q.; Zeng, X. W. Polydopamine-based surface modification of mesoporous silica nanoparticles as pH-sensitive drug delivery vehicles for cancer therapy. J. Colloid Interface Sci. 2016, 463, 279–287.CrossRefGoogle Scholar
  49. [49]
    Ai, K. L.; Liu, Y. L.; Liu, J. H.; Yuan, Q. H.; He, Y. Y.; Lu, L. H. Large-scale synthesis of Bi2S3 nanodots as a contrast agent for in vivo X-ray computed tomography imaging. Adv. Mater. 2011, 23, 4886–4891.CrossRefGoogle Scholar
  50. [50]
    Brown, A. L.; Naha, P. C.; Benavides-Montes, V.; Litt, H. I.; Goforth, A. M.; Cormode, D. P. Synthesis, X-ray opacity, and biological compatibility of ultra-high payload elemental bismuth nanoparticle X-ray contrast agents. Chem. Mater. 2014, 26, 2266–2274.CrossRefGoogle Scholar
  51. [51]
    Rabin, O.; Manuel Perez, J.; Grimm, J.; Wojtkiewicz, G.; Weissleder, R. An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat. Mater. 2006, 5, 118–122.CrossRefGoogle Scholar
  52. [52]
    Wang, S. G.; Li, X.; Chen, Y.; Cai, X. J.; Yao, H. L.; Gao, W.; Zheng, Y. Y.; An, X.; Shi, J. L.; Chen, H. R. A facile one-pot synthesis of a two-dimensional MoS2/Bi2S3 composite theranostic nanosystem for multi-modality tumor imaging and therapy. Adv. Mater. 2015, 27, 2775–2782.CrossRefGoogle Scholar
  53. [53]
    Liu, J.; Zheng, X. P.; Yan, L.; Zhou, L. J.; Tian, G.; Yin, W. Y.; Wang, L. M.; Liu, Y.; Hu, Z. B.; Gu, Z. J. et al. Bismuth sulfide nanorods as a precision nanomedicine for in vivo multimodal imaging-guided photothermal therapy of tumor. ACS Nano 2015, 9, 696–707.CrossRefGoogle Scholar
  54. [54]
    Lee, N.; Choi, S. H.; Hyeon, T. Nano-sized CT contrast agents. Adv. Mater. 2013, 25, 2641–2660.CrossRefGoogle Scholar
  55. [55]
    Peng, Y.-K.; Liu, C.-L.; Chen, H.-C.; Chou, S.-W.; Tseng, W.-H.; Tseng, Y.-J.; Kang, C.-C.; Hsiao, J.-K.; Chou, P.-T. Antiferromagnetic iron nanocolloids: A new generation in vivo T1 MRI contrast agent. J. Am. Chem. Soc. 2013, 135, 18621–18628.CrossRefGoogle Scholar
  56. [56]
    Yang, Z. Z.; Ding, X. G.; Jiang, J. Facile synthesis of magnetic–plasmonic nanocomposites as T1 MRI contrast enhancing and photothermal therapeutic agents. Nano Res. 2016, 9, 787–799.CrossRefGoogle Scholar
  57. [57]
    Tsai, M.-F.; Chang, S.-H. G.; Cheng, F.-Y.; Shanmugam, V.; Cheng, Y.-S.; Su, C.-H.; Yeh, C.-S. Au nanorod design as light-absorber in the first and second biological near-infrared windows for in vivo photothermal therapy. ACS Nano 2013, 7, 5330–5342.CrossRefGoogle Scholar
  58. [58]
    Ding, X. G.; Liow, C. H.; Zhang, M. X.; Huang, R. J.; Li, C. Y.; Shen, H.; Liu, M. Y.; Zou, Y.; Gao, N.; Zhang, Z. J. et al. Surface plasmon resonance enhanced light absorption and photothermal therapy in the second near-infrared window. J. Am. Chem. Soc. 2014, 136, 15684–15693.CrossRefGoogle Scholar
  59. [59]
    Park, J.; Brust, T. F.; Lee, H. J.; Lee, S. C.; Watts, V. J.; Yeo, Y. Polydopamine-based simple and versatile surface modification of polymeric nano drug carriers. ACS Nano 2014, 8, 3347–3356.CrossRefGoogle Scholar
  60. [60]
    Desgrosellier, J. S.; Cheresh, D. A. Integrins in cancer: Biological implications and therapeutic opportunities. Nat. Rev. Cancer 2010, 10, 9–22.CrossRefGoogle Scholar
  61. [61]
    Rüegg, C.; Alghisi, G. C. Vascular integrins: Therapeutic and imaging targets of tumor angiogenesis. In Angiogenesis Inhibition. Liersch, R.; Berdel, W. E.; Kessler, T., Eds.; Springer: Berlin Heidelberg, 2010; pp 83–101.CrossRefGoogle Scholar
  62. [62]
    Miura, Y.; Takenaka, T.; Toh, K.; Wu, S.; Nishihara, H.; Kano, M. R.; Ino, Y.; Nomoto, T.; Matsumoto, Y.; Koyama, H. et al. Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer drugs to glioblastoma through the blood–brain tumor barrier. ACS Nano 2013, 7, 8583–8592.CrossRefGoogle Scholar
  63. [63]
    Dane, K. Y.; Gottstein, C.; Daugherty, P. S. Cell surface profiling with peptide libraries yields ligand arrays that classify breast tumor subtypes. Mol. Cancer Ther. 2009, 8, 1312–1318.CrossRefGoogle Scholar
  64. [64]
    Bangari, D. S.; Mittal, S. K. Porcine adenovirus serotype 3 internalization is independent of CAR and avß3 or avß5 integrin. Virology 2005, 332, 157–166.CrossRefGoogle Scholar
  65. [65]
    Danhier, F.; Le Breton, A.; Préat, V. RGD-based strategies to target Alpha(v)Beta(3) integrin in cancer therapy and diagnosis. Mol. Pharmaceutics 2012, 9, 2961–2973.CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Xianguang Ding
    • 1
  • Xiaoxia Hao
    • 1
  • Dongdong Fu
    • 1
  • Mengxin Zhang
    • 1
  • Tian Lan
    • 1
  • Chunyan Li
    • 1
  • Renjun Huang
    • 2
  • Zhijun Zhang
    • 1
  • Yonggang Li
    • 2
  • Qiangbin Wang
    • 1
  • Jiang Jiang
    • 1
  1. 1.i-Lab and Division of Nanobiomedicine, CAS Key Laboratory of Nano-Bio Interface, CAS Center for Excellence in Nanoscience, Suzhou Institute of Nano-Tech and Nano-BionicsChinese Academy of SciencesSuzhouChina
  2. 2.Department of RadiologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina

Personalised recommendations