Layered double hydroxide monolayers for controlled loading and targeted delivery of anticancer drugs
),
Min Wei(
),
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Two-dimensional (2D) nanomaterials have gained tremendous attention in the field of biomedicine because of their high specific surface areas and fascinating physicochemical properties. Herein, 2D monolayered double hydroxide (MLDH) nanosheets were employed to localize doxorubicin (DOX), an anticancer drug, with a loading capacity of as high as 3.6 mg·mg–1 (w/w). Structural characterizations and theoretical calculations indicate that the DOX molecule is uniformly arranged and oriented at the surface of the MLDHs with a binding energy of 15.90 eV, showing significant electrostatic interaction. With the assistance of the targeting agent folic acid (FA), DOX-FA/MLDHs demonstrate targeted cellular uptake and superior anticancer behavior based on in vitro tests performed with cancer cells. In addition, this composite material exhibits a selective release toward cancer cells and good biocompatibility with normal cells, which would guarantee its practical applications in cancer therapy.
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Layered double hydroxide monolayers for controlled loading and targeted delivery of anticancer drugs
), Min Wei(
),
Abstract
Two-dimensional (2D) nanomaterials have gained tremendous attention in the field of biomedicine because of their high specific surface areas and fascinating physicochemical properties. Herein, 2D monolayered double hydroxide (MLDH) nanosheets were employed to localize doxorubicin (DOX), an anticancer drug, with a loading capacity of as high as 3.6 mg·mg–1 (w/w). Structural characterizations and theoretical calculations indicate that the DOX molecule is uniformly arranged and oriented at the surface of the MLDHs with a binding energy of 15.90 eV, showing significant electrostatic interaction. With the assistance of the targeting agent folic acid (FA), DOX-FA/MLDHs demonstrate targeted cellular uptake and superior anticancer behavior based on in vitro tests performed with cancer cells. In addition, this composite material exhibits a selective release toward cancer cells and good biocompatibility with normal cells, which would guarantee its practical applications in cancer therapy.
References(46)
Song, F.; Hu, X. L. Ultrathin cobalt–manganese layered double hydroxide is an efficient oxygen evolution catalyst. J. Am. Chem. Soc. 2014, 136, 16481–16484.
Sun, Y. F.; Cheng, H.; Gao, S.; Liu, Q. H.; Sun, Z. H.; Xiao, C.; Wu, C. Z.; Wei, S. Q.; Xie, Y. Atomically thick bismuth selenide freestanding single layers achieving enhanced thermoelectric energy harvesting. J. Am. Chem. Soc. 2012, 134, 20294–20297.
Wang, K. P.; Wang, J.; Fan, J. T.; Lotya, M.; O'Neill, A.; Fox, D.; Feng, Y. Y.; Zhang, X. Y.; Jiang, B. X.; Zhao, Q. Z. et al. Ultrafast saturable absorption of two-dimensional MoS2 nanosheets. ACS Nano 2013, 7, 9260–9267.
Li, X. H.; Zhu, J. M.; Wei, B. Q. Hybrid nanostructures of metal/two-dimensional nanomaterials for plasmon-enhanced applications. Chem. Soc. Rev. 2016, 45, 3145–3187.
Peng, X.; Peng, L. L.; Wu, C. Z.; Xie, Y. Two dimensional nanomaterials for flexible supercapacitors. Chem. Soc. Rev. 2014, 43, 3303–3323.
Tan, C. L.; Liu, Z. D.; Huang, W.; Zhang, H. Non-volatile resistive memory devices based on solution-processed ultrathin two-dimensional nanomaterials. Chem. Soc. Rev. 2015, 44, 2615–2628.
Wang, Y. L.; Cong, C. X.; Yang, W. H.; Shang, J. Z; Peimyoo, N.; Chen, Y.; Kang, J. Y.; Wang, J. P.; Huang, W.; Yu, T. Strain-induced direct–indirect bandgap transition and phonon modulation in monolayer WS2. Nano Res. 2015, 8, 2562–2572.
Chimene, D.; Alge, D. L.; Gaharwar, A. K. Two-dimensional nanomaterials for biomedical applications: Emerging trends and future prospects. Adv. Mater. 2015, 27, 7261–7284.
Lu, X.; Luo, X.; Zhang, J.; Quek, S. Y.; Xiong, Q. H. Lattice vibrations and Raman scattering in two-dimensional layered materials beyond graphene. Nano Res. 2016, 9, 3559–3597.
Tan, C. L.; Yu, P.; Hu, Y. L.; Chen, J. Z.; Huang, Y.; Cai, Y. Q.; Luo, Z. M.; Li, B.; Lu, Q. P.; Wang, L. H. et al. High-yield exfoliation of ultrathin two-dimensional ternary chalcogenide nanosheets for highly sensitive and selective fluorescence DNA sensors. J. Am. Chem. Soc. 2015, 137, 10430–10436.
Wang, Z. Y.; Zhu, W. P.; Qiu, Y.; Yi, X.; von dem Bussche, A.; Kane, A.; Gao, H. J.; Koski, K.; Hurt, R. Biological and environmental interactions of emerging two-dimensional nanomaterials. Chem. Soc. Rev. 2016, 45, 1750–1780.
Chen, Y.; Ye, D. L.; Wu, M. Y.; Chen, H. R.; Zhang, L. L.; Shi, J. L.; Wang, L. Z. Break-up of two-dimensional MnO2 nanosheets promotes ultrasensitive pH-triggered theranostics of cancer. Adv. Mater. 2014, 26, 7019–7026.
Feng, L. Y.; Wu, L.; Qu, X. G. New horizons for diagnostics and therapeutic applications of graphene and graphene oxide. Adv. Mater. 2013, 25, 168–186.
Liu, Z.; Robinson, J. T.; Sun, X. M.; Dai, H. J. PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J. Am. Chem. Soc. 2008, 130, 10876–10877.
Liu, T.; Wang, C.; Gu, X.; Gong, H.; Cheng, L.; Shi, X. Z.; Feng, L. Z.; Sun, B. Q.; Liu, Z. Drug delivery with PEGylated MoS2 nano-sheets for combined photothermal and chemotherapy of cancer. Adv. Mater. 2014, 26, 3433–3440.
Wang, H.; Yang, X. Z.; Shao, W.; Chen, S. C.; Xie, J. F.; Zhang, X. D.; Wang, J.; Xie, Y. Ultrathin black phosphorus nanosheets for efficient singlet oxygen generation. J. Am. Chem. Soc. 2015, 137, 11376–11382.
Novoselov, K. S.; Geim, A. K.; Morozov, S. V.; Jiang, D.; Zhang, Y.; Dubonos, S. V.; Grigorieva, I. V.; Firsov, A. A. Electric field effect in atomically thin carbon films. Science 2004, 306, 666–669.
Cheng, L.; Liu, J. J.; Gu, X.; Gong, H.; Shi, X. Z.; Liu, T.; Wang, C.; Wang, X. Y.; Liu, G.; Xing, H. Y. 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.
Feng, L. Y.; Li, W.; Ren, J. S.; Qu, X. G. Electrochemically and DNA-triggered cell release from ferrocene/β-cyclodextrin and aptamer modified dualfunctionalized graphene substrate. Nano Res. 2015, 8, 887–899.
Li, M.; Zhao, A. D.; Dong, K.; Li, W.; Ren, J. S.; Qu, X. G. Chemically exfoliated WS2 nanosheets efficiently inhibit amyloid β-peptide aggregation and can be used for photothermal treatment of Alzheimer's disease. Nano Res. 2015, 8, 3216–3227.
Wang, Q.; Tay, H. H.; Zhong, Z. Y.; Luo, J. Z.; Borgna, A. Synthesis of high-temperature CO2 adsorbents from organo-layered double hydroxides with markedly improved CO2 capture capacity. EnergyEnviron. Sci. 2012, 5, 7526–7530.
Qiao, Y. Q.; Wang, J. Y.; Huang, L.; Zheng, Q. W.; O'Hare, D.; Wang, Q. LDH/MgCO3 hybrid multilayer on an aluminium substrate as a novel high-temperature CO2 adsorbent. RSC Adv. 2015, 5, 82777–82780.
Williams, G. R.; Fogg, A. M.; Sloan, J.; Taviot-Guého, C.; O'Hare, D. Staging during anion-exchange intercalation into[LiAl2(OH)6]Cl·yH2O: Structural and mechanistic insights. Dalton Trans. 2007, 3499–3506.
Varadwaj, G. B. B.; Nyamori, V. O. Layered double hydroxide- and graphene-based hierarchical nanocomposites: Synthetic strategies and promising applications in energy conversion and conservation. Nano Res. 2016, 9, 3598–3621.
Evans, D. G.; Duan, X. Preparation of layered double hydroxides and their applications as additives in polymers, as precursors to magnetic materials and in biology and medicine. Chem. Commun. 2006, 485–496.
Li, L.; Gu, W. Y.; Liu, J.; Yan, S. Y.; Xu, Z. P. Amine-functionalized SiO2 nanodot-coated layered double hydroxide nanocomposites for enhanced gene delivery. Nano Res. 2015, 8, 682–694.
Liu, Z. L.; Tian, D. Y.; Li, S. P.; Li, X. D.; Lu, T. H. MTX/LDHs hybrids synthesized from reverse microemulsions: Particle control and bioassay study. Int. J. Pharm. 2014, 473, 414–425.
Li, L.; Gu, W. Y.; Chen, J. Z.; Chen, W. Y.; Xu, Z. P. Co-delivery of siRNAs and anti-cancer drugs using layered double hydroxide nanoparticles. Biomaterials 2014, 35, 3331–3339.
Park, D. H.; Kim, J. E.; Oh, J. M.; Shul, Y. G.; Choy, J. H. DNA core@inorganic shell. J. Am. Chem. Soc. 2010, 132, 16735–16736.
Liang, R. Z.; Tian, R.; Ma, L. N.; Zhang, L. L.; Hu, Y. L.; Wang, J.; Wei, M.; Yan, D.; Evans, D. G.; Duan, X. A supermolecular photosensitizer with excellent anticancer performance in photodynamic therapy. Adv. Funct. Mater. 2014, 24, 3144–3151.
Song, F.; Hu, X. L. Exfoliation of layered double hydroxides for enhanced oxygen evolution catalysis. Nat. Commun. 2014, 5, 4477.
Wang, Q.; Tang, S. V. Y.; Lester, E.; O'Hare, D. Synthesis of ultrafine layered double hydroxide (LDHs) nanoplates using a continuous-flow hydrothermal reactor. Nanoscale 2013, 5, 114–117.
Yan, Y. X.; Liu, Q.; Wang, J.; Wei, J. B.; Gao, Z.; Mann, T.; Li, Z. S.; He, Y.; Zhang, M.; Liu, L. H. Single-step synthesis of layered double hydroxides ultrathin nanosheets. J. Colloid Interface Sci. 2012, 371, 15–19.
Yan, D. P.; Lu, J.; Ma, J.; Wei, M.; Evans, D. G.; Duan, X. Reversibly thermochromic, fluorescent ultrathin films with a supramolecular architecture. Angew. Chem., Int. Ed. 2011, 50, 720–723.
Zhang, L. M.; Xia, J. G.; Zhao, Q. H.; Liu, L. W.; Zhang, Z. J. Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs. Small 2010, 6, 537–544.
Zhang, Z. J.; Wang, J.; Nie, X.; Wen, T.; Ji, Y. L.; Wu, X. C.; Zhao, Y. L.; Chen, C. Y. Near infrared laser-induced targeted cancer therapy using thermoresponsive polymer encapsulated gold nanorods. J. Am. Chem. Soc. 2014, 136, 7317–7326.
Tian, Y. H.; Li, S. P.; Song, J.; Ji, T. J.; Zhu, M. T.; Anderson, G. J.; Wei, J. Y.; Nie, G. J. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials 2014, 35, 2383–2390.
Yu, J. F.; Martin, B. R.; Clearfield, A.; Luo, Z. P.; Sun, L. Y. One-step direct synthesis of layered double hydroxide single-layer nanosheets. Nanoscale 2015, 7, 9448–9451.
Liu, Z.; Sun, X. M.; Nakayama-Ratchford, N.; Dai, H. J. Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery. ACS Nano 2007, 1, 50–56.
Zhang, S. T; Yan, H.; Wei, M.; Evans, D. G.; Duan, X. Valence force field for layered double hydroxide materials based on the parameterization of octahedrally coordinated metal cations. J. Phys. Chem. C2012, 116, 3421–3431.
Andersen, H. C. Molecular dynamics simulations at constant pressure and/or temperature. J. Chem. Phys. 1980, 72, 2384–2393.
Berendsen, H. J. C.; Postma, J. P. M.; Van Gunsteren, W. F.; DiNola, A.; Haak, J. R. Molecular dynamics with coupling to an external bath. J. Chem. Phys. 1984, 81, 3684–3690.
Allen, M. P.; Tildesley, D. J. Computer Simulation of Liquids; Clarendon Press: Oxford, U. K., 1987.
Frenkel, D.; Smit, B. Understanding Molecular Simulation: From Algorithms to Applications; 2nd ed., Academic Press: San Diego, 2002.
Liang, R. Z.; Xu, S. M.; Yan, D. P.; Shi, W. Y.; Tian, R.; Yan, H.; Wei, M.; Evans, D. G.; Duan, X. CdTe quantum dots/layered double hydroxide ultrathin films with multicolor light emission via layer-by-layer assembly. Adv. Funct. Mater. 2012, 22, 4940–4948.
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Acknowledgements
This work was supported by National Natural Science Foundation of China (NSFC) (Nos. 21671013 and 21601010), the National Basic Research Program of China (973 Program) (No. 2014CB932103), the Fundamental Research Funds for the Central Universities (Nos. YS 1406, ZY1628, and buctrc201611) and Beijing Natural Science Foundation (No. 2174082).
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