logo

SCIENCE CHINA Materials, Volume 60, Issue 6: 554-562(2017) https://doi.org/10.1007/s40843-017-9056-1

Albumin nanoreactor-templated synthesis of Gd2O3/CuS hybrid nanodots for cancer theranostics

More info
  • ReceivedApr 15, 2017
  • AcceptedMay 25, 2017
  • PublishedJun 2, 2017

Abstract

It remains a great challenge to explore the facile way to fabricate multi-component nanoparticles in theranostic nanomedicine. Herein, an albumin nanoreactor templated synthesis of theranostic Gd2O3/CuS hybrid nanodots (NDs) has been developed for multimodal imaging guided photothermal tumor ablation. Gd2O3/CuS NDs are found to possess particle size of 4.4 ± 1.1 nm, enhanced longitudinal relaxivity, effective photothermal conversion of 45.5%, as well as remarkable near-infrared fluorescence (NIRF) from Cy7.5-conjugated on albumin corona. The Gd2O3/CuS NDs further exhibited good photostability, enhanced cellular uptake, and preferable tumor accumulation. Thus, the Gd2O3/CuS NDs generate remarkable NIRF imaging and T1-weighted magnetic resonance (MR) imaging, and simultaneously result in effective photothermal tumor ablation upon irradiation. The albumin nanoreactor provides a facile and general strategy to synthesize multifunctional nanoparticles for cancer theranostics.


Funded by

National Natural Science Foundation of China(31422021,51473109,81501585)

National Basic Research Program of China(2014CB931900)

Natural Science Foundation of Jiangsu Province of China(BK20150348)

Natural Science Foundation of the Jiangsu Higher Education Institutions of China(15KJB310019)

China Postdoctoral Science Foundation(2015M570475,2016T90496)

Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)

Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases

Open Fund of CAS Key Laboratory of Nano-Bio Interface(16NBI02)

Jiangsu Undergraduates Innovation and Entrepreneurship Program(20150285075Y)


Acknowledgment

This work was financially supported by the National Natural Science Foundation of China (31422021, 51473109, and 81501585), National Basic Research Program of China (2014CB931900), Natural Science Foundation of Jiangsu Province of China (BK20150348), Natural Science Foundation of the Jiangsu Higher Education Institutions of China (15KJB310019), China Postdoctoral Science Foundation (2015M570475 and 2016T90496), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Open Fund of CAS Key Laboratory of Nano-Bio Interface (16NBI02), and Jiangsu Undergraduates Innovation and Entrepreneurship Program (20150285075Y).


Interest statement

The authors declare that they have no conflict of interest.


Contributions statement

Chen H and Shen J designed the study; Wen R prepared the samples; Wen R, Lv X and Bai X performed the characterizations, cell and animal experiments; Wen R and Li Y carried out the imaging experiments; Ke H and Chen H wrote the paper with support from Yang T and Tang Y. All authors contributed to the general discussion.


Author information

Ru Wen is currently a Master candidate at the Department of Radiology, Second Affiliated Hospital of Soochow University. Her research interests include the development and medical application of novel magnetic resonance imaging agents.


Xiaoyan Lv is currently a Master candidate at the College of Pharmaceutical Sciences, Soochow University. Her research interests focus on the development of multifunctional nanoparticles for multimodal cancer imaging and photothermal therapy.


Hengte Ke is currently an assistant professor at the College of Pharmaceutical Sciences, Soochow University. He received his PhD degree of biomedical engineering from Harbin Institute of Technology in 2014, and worked as a visiting scholar at the University of Massachusetts, USA from 2012 to 2013. His research focuses on theranostic nanomedicine and multimodal imaging probes.


Junkang Shen is currently a full professor and chief physician at the Department of Radiology, Second Affiliated Hospital of Soochow University. He received his Master degree of medicine in 1999. His research focuses on clinical magnetic resonance imaging diagnosis.


Huabing Chen is currently a full professor at the College of Pharmaceutical Sciences, Soochow University. He received his PhD degree of biopharmaceutical engineering in 2008 from Huazhong University of Science & Technology. Then he worked as a postdoc at the University of Texas Southwestern Medical Center at Dallas and University of Tokyo from 2008 to 2012. His research interests include biomimetic protein nanoparticles for cancer theranostics and self-assembled nanoparticles for photo-induced cancer therapy.


Supplement

Supplementary information

Additional experimental details and supporting data are available in the online version of the paper.


References

[1] Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer, 2005, 5: 161-171 CrossRef PubMed Google Scholar

[2] Wang X, Yang L, Chen ZG, et al. Application of nanotechnology in cancer therapy and imaging. CA-A Cancer J Clinicians, 2008, 58: 97-110 CrossRef PubMed Google Scholar

[3] Nie S, Xing Y, Kim GJ, et al. Nanotechnology applications in cancer. Annu Rev Biomed Eng, 2007, 9: 257-288 CrossRef Google Scholar

[4] Farokhzad OC, Langer R. Nanomedicine: Developing smarter therapeutic and diagnostic modalities. Adv Drug Deliver Rev, 2006, 58: 1456-1459 CrossRef PubMed Google Scholar

[5] Barreto JA, O'Malley W, Kubeil M, et al. Nanomaterials: applications in cancer imaging and therapy. Adv Mater, 2011, 23: H18-H40 CrossRef PubMed Google Scholar

[6] Warner S. Diagnostics plus therapy = theranostics. Scientist, 2004, 18: 38–39. Google Scholar

[7] Mura S, Couvreur P. Nanotheranostics for personalized medicine. Adv Drug Deliver Rev, 2012, 64: 1394-1416 CrossRef PubMed Google Scholar

[8] Chen X, Gambhir SS, Cheon J. Theranostic nanomedicine. Acc Chem Res, 2011, 44: 841-841 CrossRef PubMed Google Scholar

[9] Cheng L, Liu J, Gu X, et al. PEGylated WS2 Nanosheets as a multifunctional theranostic agent for in vivo dual-modal CT/photoacoustic imaging guided photothermal therapy. Adv Mater, 2014, 26: 1886-1893 CrossRef PubMed Google Scholar

[10] Liu T, Shi S, Liang C, et al. Iron oxide decorated MoS2 nanosheets with double PEGylation for chelator-free radiolabeling and multimodal imaging guided photothermal therapy. ACS Nano, 2015, 9: 950-960 CrossRef PubMed Google Scholar

[11] Sumer B, Gao J. Theranostic nanomedicine for cancer. Nanomedicine, 2008, 3: 137-140 CrossRef PubMed Google Scholar

[12] Melancon MP, Zhou M, Li C. Cancer theranostics with near-infrared light-activatable multimodal nanoparticles. Acc Chem Res, 2011, 44: 947-956 CrossRef PubMed Google Scholar

[13] Li Y, Bai X, Xu M, et al. Photothermo-responsive Cu7S4@polymer nanocarriers with small sizes and high efficiency for controlled chemo/photothermo therapy. Sci China Mater, 2016, 59: 254-264 CrossRef Google Scholar

[14] Mathiyazhakan M, Upputuri PK, Sivasubramanian K, et al. In situ synthesis of gold nanostars within liposomes for controlled drug release and photoacoustic imaging. Sci China Mater, 2016, 59: 892-900 CrossRef Google Scholar

[15] Tang Y, Hu J, Elmenoufy AH, et al. Highly efficient FRET system capable of deep photodynamic therapy established on X-ray excited mesoporous LaF3:Tb scintillating nanoparticles. ACS Appl Mater Interfaces, 2015, 7: 12261-12269 CrossRef Google Scholar

[16] Elmenoufy AH, Tang Y, Hu J, et al. A novel deep photodynamic therapy modality combined with CT imaging established via X-ray stimulated silica-modified lanthanide scintillating nanoparticles. Chem Commun, 2015, 51: 12247-12250 CrossRef PubMed Google Scholar

[17] Mou J, Chen Y, Ma M, et al. Facile synthesis of liposome/Cu2−xS-based nanocomposite for multimodal imaging and photothermal therapy. Sci China Mater, 2015, 58: 294-301 CrossRef Google Scholar

[18] Wang Y, Yang T, Ke H, et al. Smart albumin-biomineralized nanocomposites for multimodal imaging and photothermal tumor ablation. Adv Mater, 2015, 27: 3874-3882 CrossRef PubMed Google Scholar

[19] Wang Z, Huang P, Jacobson O, et al. Biomineralization-inspired synthesis of copper sulfide–ferritin nanocages as cancer theranostics. ACS Nano, 2016, 10: 3453-3460 CrossRef Google Scholar

[20] Xie J, Zheng Y, Ying JY. Protein-directed synthesis of highly fluorescent gold nanoclusters. J Am Chem Soc, 2009, 131: 888-889 CrossRef PubMed Google Scholar

[21] Sun C, Yang H, Yuan Y, et al. Controlling assembly of paired gold clusters within apoferritin nanoreactor for in vivo kidney targeting and biomedical imaging. J Am Chem Soc, 2011, 133: 8617-8624 CrossRef PubMed Google Scholar

[22] Yang T, Wang Y, Ke H, et al. Protein-nanoreactor-assisted synthesis of semiconductor nanocrystals for efficient cancer theranostics. Adv Mater, 2016, 28: 5923-5930 CrossRef PubMed Google Scholar

[23] Tanford C, Buzzell JG, Rands DG, et al. The reversible expansion of bovine serum albumin in acid solutions. J Am Chem Soc, 1955, 77: 6421-6428 CrossRef Google Scholar

[24] Bro P, Singer SJ, Sturtevant JM. On the aggregation of bovine serum albumin in acid solutions. J Am Chem Soc, 1958, 80: 389-393 CrossRef Google Scholar

[25] Bridot JL, Faure AC, Laurent S, et al. Hybrid gadolinium oxide nanoparticles:  multimodal contrast agents for in vivo imaging. J Am Chem Soc, 2007, 129: 5076-5084 CrossRef PubMed Google Scholar

[26] Park JY, Baek MJ, Choi ES, et al. Paramagnetic ultrasmall gadolinium oxide nanoparticles as advanced T1 MRI contrast agent: account for large longitudinal relaxivity, optimal particle diameter, and in vivo T1 MR images. ACS Nano, 2009, 3: 3663-3669 CrossRef PubMed Google Scholar

[27] Li F, Zhi D, Luo Y, et al. Core/shell Fe3O4/Gd2O3 nanocubes as T1T2 dual modal MRI contrast agents. Nanoscale, 2016, 8: 12826-12833 CrossRef PubMed ADS Google Scholar

[28] Eurov DA, Kurdyukov DA, Kirilenko DA, et al. Core–shell monodisperse spherical mSiO2/Gd2O3:Eu3+@mSiO2 particles as potential multifunctional theranostic agents. J Nanopart Res, 2015, 17: 82 CrossRef ADS Google Scholar

[29] Xu Z, Gao Y, Huang S, et al. A luminescent and mesoporous core-shell structured Gd2O3 : Eu3+@nSiO2@mSiO2 nanocomposite as a drug carrier. Dalton Trans, 2011, 40: 4846 CrossRef PubMed Google Scholar

[30] Ananta JS, Godin B, Sethi R, et al. Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast. Nat Nanotech, 2010, 5: 815-821 CrossRef PubMed ADS Google Scholar

[31] Chu KF, Dupuy DE. Thermal ablation of tumours: biological mechanisms and advances in therapy. Nat Rev Cancer, 2014, 14: 199-208 CrossRef PubMed Google Scholar

[32] Hessel CM, Pattani VP, Rasch M, et al. Copper selenide nanocrystals for photothermal therapy. Nano Lett, 2011, 11: 2560-2566 CrossRef PubMed ADS Google Scholar

  • Figure 1

    Schematic illustration of (a) albumin nanoreactor-templated construction of Gd2O3/CuS NDs and (b) their use for cancer theranostics.

  • Figure 2

    (a) TEM image, (b) size distribution and (c) UV-vis absorbance spectrum of Gd2O3/CuS NDs; (d) relaxivity of Gd2O3/CuS NDs from T1-weighted maps in MR phantoms; (e) temperature elevations of Gd2O3/CuS NDs in 5 min at various Cu concentrations under 785 nm irradiation (1.5 W cm−2); (f) temperature elevations of Gd2O3/CuS NDs and Au NRs under five laser ON/OFF cycles (785 nm,1.5 W cm−2).

  • Figure 3

    (a) Total amount of Cu internalized by 4T1 cells after 6 and 24 h incubation with Gd2O3/CuS NDs, respectively; (b) endocytic pathway of Gd2O3/CuS NDs into 4T1 cells; (c) intracellular distribution of Cy7.5-labelled Gd2O3/CuS NDs in 4T1 cells stained by Lysotracker and Hoechst 33342; (d) cytotoxicity of Gd2O3/CuS NDs upon NIR irradiation or not (785 nm,1.5 W cm−2).

  • Figure 4

    (a) In vivo NIRF imaging and (b) calculated intensity of the mice injected with Cy7.5-Gd2O3/CuS NDs during 168 h post-injection; (c) in vivo MR imaging and (d) calculated MR intensity of the tumor areas (highlighted in yellow circles) from the mice injected with Gd2O3/CuS NDs and Gd-DTPA at 0, 2, 12 and 24 h post-injection, respectively (*p<0.05, **p<0.01).

  • Figure 5

    (a) Infrared thermography and (b) corresponding temperature elevation at tumor region of the mice injected with Gd2O3/CuS NDs at various doses under 1.5 W cm−2 irradiation (785 nm,5 min); (c) tumor growth profiles of the mice treated with Gd2O3/CuS NDs at different doses under 785 nm irradiation or not, (d) photographs of the tumors extracted from the mice at the end of experiment.

Copyright 2020 Science China Press Co., Ltd. 《中国科学》杂志社有限责任公司 版权所有

京ICP备18024590号-1