Modifying layered double hydroxide nanoparticles for tumor imaging and therapy

  • Li Li
  • Bei Li
  • Wenyi Gu
  • Zhi Ping XuEmail author


Tumor theranostics (a portmanteau of therapeutics and diagnostics) is now achieved in various ways with complex nanoparticle systems. Layered double hydroxide (LDH) nanoparticles are effective at drug/gene delivery and as imaging agents in potential tumor theranostics. This mini-review paper summarizes recent progress in developing LDH nanoparticles as a pH-sensitive magnetic resonance imaging (MRI) contrast agent, as a positron emission tomography (PET) imaging agent, and as a co-delivery platform for two therapeutic agents for tumor diagnosis and therapy. These results have indicated clearly the potential application of LDH nanoparticles for simultaneous diagnosis and treatment of cancers.


Co-delivery of Therapeutic Agents Imaging Agent Layered Double Hydroxide MRI PET Tumor Theranostics 



This work was supported financially by an Australian Research Council (ARC) grant (DP170104643) and the Australian Government Research Training Program Scholarship (RTP). The authors acknowledge the facilities and the assistance of Queensland Node of the Australian National Fabrication Facility (ANFF-Q), the University of Queensland.


  1. Caravan, P., Farrar, C. T., Frullano, L., & Uppal, R. (2009). Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium- and manganese-based T1 contrast agents. Contrast Media & Molecular Imaging, 4, 89–100.CrossRefGoogle Scholar
  2. Chen, C., Yee, L. K., Gong, H., Zhang, Y., & Xu, R. (2013). A facile synthesis of strong near infrared fluorescent layered double hydroxide nanovehicles with an anticancer drug for tumor optical imaging and therapy. Nanoscale, 5, 4314–4320.CrossRefGoogle Scholar
  3. Chen, J. (2011). Multiple signal pathways in obesity-associated cancer. Obesity Reviews, 12, 1063–1070.CrossRefGoogle Scholar
  4. Chen, J. Z., Shao, R. F., Li, L., Xu, Z. P., & Gu, W. Y. (2014). Effective inhibition of colon cancer cell growth with MgAl-layered double hydroxide (LDH) loaded 5-FU and PI3K/mTOR dual inhibitor BEZ-235 through apoptotic pathways. International Journal of Nanomedecine, 9, 3403–3411.Google Scholar
  5. Chen, M., Cooper, H. M., Zhou, J. Z., Bartlett, P. F., & Xu, Z. P. (2013). Reduction in the size of layered double hydroxide nanoparticles enhances the efficiency of siRNA delivery. Journal of Colloid And Interface Science, 390, 275–281.CrossRefGoogle Scholar
  6. Choi, G., Piao, H., Alothman, Z. A., Vinu, A., Yun, C. O., & Choy, J. H. (2016). Anionic clay as the drug delivery vehicle: tumor targeting function of layered double hydroxide-methotrexate nanohybrid in C33A orthotopic cervical cancer model. International Journal of Nanomedicine, 11, 337–348.CrossRefGoogle Scholar
  7. Choi, S. J., Oh, J. M., & Choy, J. H. (2008). Anticancer drug-layered hydroxide nanohybrids as potent cancer chemotherapy agents. Journal of Physics and Chemistry of Solids, 69, 1528–1532.Google Scholar
  8. Choi, S. J., & Choy, J. H. (2011). Layered double hydroxide nanoparticles as target-specific delivery carriers: uptake mechanism and toxicity. Nanomedicine, 6, 803–814.Google Scholar
  9. Chow, L. W. C., & Loo, W. T. Y. (2003). The differential effects of cyclophosphamide, epirubicin and 5-fluorouracil on apoptotic marker (CPP-32), proapoptotic protein (p21WAF-1) and anti-apoptotic protein (bcl-2) in breast cancer cells. Breast Cancer Research Treatment, 80, 239–244.Google Scholar
  10. Choy, J. H., Jung, J. S., Oh, J. M., Park, M., Jeong, J., Kang, Y. K., & Han, O. J. (2004). Layered double hydroxide as an efficient drug reservoir for folate derivatives. Biomaterials, 25, 3059–3064.CrossRefGoogle Scholar
  11. Chumakova, O. V., Liopo, A. V., Mark, E. B., & Esenaliev, R. O. (2006). Effect of 5-fluorouracil, optison and ultrasound on MCF-7 cell viability. Ultrasound in Medicine and Biology, 32, 751–758.CrossRefGoogle Scholar
  12. Copur, S., Aiba, K., Drake, J. C., Allegra, C. J., & Chu, E. (1995). Thymidylate synthase gene amplification in human colon cancer cell lines resistant to 5-fluorouracil. Biochemical Pharmacology, 49, 1419–1426.CrossRefGoogle Scholar
  13. Desigaux, L., Richard, P., Pitard, B., Belkacem, M. B., Cellier, J., Leroux, F., Taviot-Guého, C., Léone, P., & Cario, L. (2006). Self-assembly and characterization of layered double hydroxide/DNA hybrids. Nano Letters, 6, 199–204.CrossRefGoogle Scholar
  14. Donahue, K. M., Burstein, D., Manning, W. J., & Gray, M. L. (1994). Studies of Gd-DTPA relaxivity and proton exchange rates in tissue. Magnetic Resonance in Medicine, 32, 66–76.CrossRefGoogle Scholar
  15. Gu, Z., Zuo, H. L., Li, L., Wu, A. H., & Xu, Z. P. (2015). Pre-coating layered double hydroxide nanoparticles with albumin to improve colloidal stability and cellular uptake. Journal of Materials Chemistry B, 3, 3331–3339.CrossRefGoogle Scholar
  16. Heffern, M. C., Matosziuk, L. M., & Meade, M. J. (2014). Lanthanide probes for bioresponsive imaging. Chemical Reviews, 114, 4496–4539.CrossRefGoogle Scholar
  17. Ito, A., Fujioka, M., Yoshida, T., Wakamatsu, K., Ito, S., Yamashita, T., Jimbow, K., & Honda, H. (2007). 4-S-cysteaminylphenol-loaded magnetite cationic liposomes for combination therapy of hyperthermia with chemotherapy against malignant melanoma. Cancer Science, 98, 424–430.CrossRefGoogle Scholar
  18. Johnston, P. G., Lenz, H. J., Leichman, C. G., Danenberg, K. D., Allegra, C. J., Danenberg, P. V., & Leichman, L. (1995). Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. Cancer Research, 55, 1407–1412.Google Scholar
  19. Khan, A. I., Lei, L., Norquist, A. J., & Hare, D. (2001). Intercalation and controlled release of pharmaceutically active compounds from a layered double hydroxide. Chemical Communications, 0, 2342–2343.CrossRefGoogle Scholar
  20. Lee, J. H., Jung, D. Y., Kim, E., & Ahn, T. K. (2014). Fluorescein dye intercalated layered double hydroxides for chemically stabilized photoluminescent indicators on inorganic surfaces. Dalton Transcations, 43, 8543–8548.CrossRefGoogle Scholar
  21. Li, B., Gu, Z., Kurniawan, N., Chen, W. Y., & Xu, Z. P. (2017). Manganese-based layered double hydroxide nanoparticle as a T1-MRI contrast agent with ultrasensitive pH response and high relaxivity. Advanced Materials, 29, 1700373.CrossRefGoogle Scholar
  22. Li, D., Zhang, Y. T., Yu, M., Guo, J., Chaudhary, D., & Wang, C. C. (2013). Cancer therapy and fluorescence imaging using the active release of doxorubicin from MSPs/Ni-LDH folate targeting nanoparticles. Biomaterials, 34, 7913–7922.CrossRefGoogle Scholar
  23. Li, L., Gu, W., Chen, J., Chen, W., & Xu, Z. P. (2014). Co-delivery of siRNAs and anti-cancer drugs using layered double hydroxide nanoparticles. Biomaterials, 35, 3331–3339.CrossRefGoogle Scholar
  24. Li, L., Gu, W., Liu, J., & Xu, Z. P. (2015). Amine-functionalized SiO2 nanodot-coated layered double hydroxide nanocomposites for enhanced gene delivery. Nano Research, 8, 682–694.CrossRefGoogle Scholar
  25. Li, X. S., Ke, M. R., Huang, W., Ye, C. H., & Huang, J. D. (2015). A pH-responsive layered double hydroxide (LDH)–phthalocyanine nanohybrid for efficient photodynamic therapy. Chemistry - A European Journal, 21, 3310–3317.CrossRefGoogle Scholar
  26. Manara, M. C., Nicoletti, G., Zambelli, D., Ventura, S., Guerzoni, C., Landuzzi, L., Lollini, P. L., Maira, S. M., García-Echeverría, C., Mercuri, M., Picci, P., & Scotlandi, K. (2010). NVP-BEZ235 as a new therapeutic option for sarcomas. Clinical Cancer Research, 16, 530–540.CrossRefGoogle Scholar
  27. Mei, X., Ma, J., Bai, X., Zhang, X., Zhang, S., Liang, R., Wei, M., Evans, D. G., & Duan, X. (2018a). A bottom-up synthesis of rare-earth-hydrotalcite monolayer nanosheets toward multimode imaging and synergetic therapy. Chemical Science, 9, 5630–5639.CrossRefGoogle Scholar
  28. Mei, X., Wang, W., Yan, L., Hu, T., Liang, R., Yan, D., Wei, M., Evans, D. G., & Duan, X. (2018b). Hydrotalcite monolayer toward high performance synergistic dual-modal imaging and cancer therapy. Biomaterials, 165, 14–24.CrossRefGoogle Scholar
  29. Park, A.-Y., Kwon, H., Woo, A. J., & Kim, S. J. (2005). Layered double hydroxide surface modified with (3-aminopropyl)-triethoxysilane by covalent bonding. Advanced Materials, 17, 106–109.CrossRefGoogle Scholar
  30. Shi, S. X., Fliss, B., Gu, Z., Zhu, Y., Hong, H., Valdovinos, H. F., Hernandez, R., Goel, S., Luo, H. M., Chen, F., Barnhart, T. E., Nickles, R. J., Xu, Z. P., & Cai, W. B. (2015). Chelator-free labeling of layered double hydroxide nanoparticles for in vivo PET imaging. Scientific Reports, 5(16930), 1–10.Google Scholar
  31. Wang, L., Xing, H. Y., Zhang, S. J., Ren, Q. G., Pan, L. M., Zhang, K., Bu, W. B., Zheng, X. P., Zhou, L. P., Peng, W. J., Hua, Y. Q., & Shi, J. L. (2013). A Gd-doped Mg-Al-LDH/Au nanocomposite for CT/MR bimodal imagings and simultaneous drug delivery. Biomaterials, 34, 3390–3401.CrossRefGoogle Scholar
  32. Wang, Q., & O'Hare, D. (2012). Recent advances in the synthesis and application of layered double hydroxide (LDH) nanosheets. Chemical Reviews, 112, 4124–4155.CrossRefGoogle Scholar
  33. Wong, Y., Cooper, H. M., Zhang, K., Chen, M., Bartlett, P., & Xu, Z. P. (2012). Efficiency of layered double hydroxide nanoparticle-mediated delivery of siRNA is determined by nucleotide sequence. Journal of Colloid And Interface Science, 369, 453–459.CrossRefGoogle Scholar
  34. Wu, P., & Hu, Y. Z. (2010). PI3K/Akt/mTOR pathway inhibitors in cancer: a perspective on clinical progress. Current Medicinal Chemistry, 17, 4326–4341.CrossRefGoogle Scholar
  35. Xu, Z. P., & Lu, G. Q. (2005). Hydrothermal synthesis of layered double hydroxides (LDHs) from mixed MgO and Al2O3: LDH formation mechanism. Chemistry of Materials, 17, 1055–1062.Google Scholar
  36. Xu, Z. P., Stevenson, G. S., Lu, C. Q., & Lu, G. Q. (2006a). Dispersion and size control of layered double hydroxide nanoparticles in aqueous solutions. The Journal of Physical Chemistry B, 110, 16923–16929.Google Scholar
  37. Xu, Z. P., Stevenson, G. S., Lu, C. Q., Lu, G. Q., Bartlett, P. F., & Gray, P. P. (2006b). Stable suspension of layered double hydroxide nanoparticles in aqueous solution. Journal of the American Chemical Society, 128, 36–37.Google Scholar
  38. Xu, Z. P., Jin, Y. G., Liu, S. M., Hao, Z. P., & Lu, G. Q. (2008a). Surface charging of layered double hydroxides during dynamic interactions of anions at the interfaces. Journal of Colloid And Interface Science, 326, 522–529.Google Scholar
  39. Xu, Z. P., Niebert, M., Porazik, K., Walker, T. L., Cooper, H. M., Middelberg, A. P. J., Gray, P. P., Bartlett, P. F., & Lu, G. Q. (2008b). Subcellular compartment targeting of layered double hydroxide nanoparticles. Journal of Controlled Release, 130, 86–94.Google Scholar
  40. Zuo, H. L., Chen, W., Li, B., Xu, K., Cooper, H., Gu, Z., & Xu, Z. P. (2017). MnAl- layered double hydroxide nanoparticles as a dual-functional platform for magnetic resonance imaging and siRNA delivery. Chemistry – A European Journal, 23, 14299–14306.CrossRefGoogle Scholar

Copyright information

© The Clay Minerals Society 2019

Authors and Affiliations

  1. 1.Australian Institute for Bioengineering and NanotechnologyThe University of QueenslandBrisbaneAustralia

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