Ultra-small MoS2 nanodots with rapid body clearance for photothermal cancer therapy
- 921 Downloads
- 27 Citations
Abstract
The clinical translation of many inorganic nanomaterials is severely hampered by toxicity issues because of the long-term retention of these nanomaterials in the body. In this study, we developed a bio-clearable theranostic agent based on ultra-small MoS2 nanodots, which were synthesized by a facile bottom-up approach through one-step solvothermal decomposition of ammonium tetrathiomolybdate. After modification by glutathione (GSH), the obtained MoS2-GSH nanodots exhibited sub-10-nm hydrodynamic diameters without aggregation in various physiological buffers. Without showing appreciable in vitro toxicity, such MoS2-GSH nanodots with strong near-infrared (NIR) absorbance could induce remarkable photothermal ablation of cancer cells. Upon intravenous (i.v.) injection, efficient tumor accumulation of MoS2-GSH nanodots was observed by photoacoustic imaging, and further confirmed by analysis of the biodistribution of Mo. Notably, the MoS2-GSH nanodots, in contrast to conventional MoS2 nanoflakes with larger sizes, showed rather efficient body clearance via urine, where the majority of the injected dose was cleared within just seven days. Photothermal ablation of tumors on mice was then realized with the MoS2-GSH nanodots, achieving excellent therapeutic efficacy. This study presents a new type of ultra-small nanoparticle with efficient tumor homing/treatment abilities, as well as rapid body clearance behavior, making it promising for cancer theranostics without long-term toxicity concerns.
Keywords
ultra-small MoS2 nanodots photoacoustic imaging rapid body clearance photothermal therapyPreview
Unable to display preview. Download preview PDF.
Supplementary material
References
- [1]Davis, M. E.; Chen, Z.; Shin, D. M. Nanoparticle therapeutics: An emerging treatment modality for cancer. Nat. Rev. Drug Discov. 2008, 7, 771–782.CrossRefGoogle Scholar
- [2]Cheng, L.; Wang, C.; Feng, L. Z.; Yang, K.; Liu, Z. Functional nanomaterials for phototherapies of cancer. Chem. Rev. 2014, 114, 10869–10939.CrossRefGoogle Scholar
- [3]Bhaumik, J.; Mittal, A. K.; Banerjee, A.; Chisti, Y.; Banerjee, U. C. Applications of phototheranostic nanoagents in photodynamic therapy. Nano Res. 2015, 8, 1373–1394.CrossRefGoogle Scholar
- [4]Cobley, C. M.; Chen, J. Y.; Cho, E. C.; Wang, L. V.; Xia, Y. N. Gold nanostructures: A class of multifunctional materials for biomedical applications. Chem. Soc. Rev. 2011, 40, 44–56.CrossRefGoogle Scholar
- [5]William, W. Y.; Chang, E.; Drezek, R.; Colvin, V. L. Water-soluble quantum dots for biomedical applications. Biochem. Biophys. Res. Commun. 2006, 348, 781–786.CrossRefGoogle Scholar
- [6]Cheng, L.; Wang, C.; Liu, Z. Upconversion nanoparticles and their composite nanostructures for biomedical imaging and cancer therapy. Nanoscale 2013, 5, 23–37.CrossRefGoogle Scholar
- [7]Li, Z. W.; Wang, C.; Cheng, L.; Gong, H.; Yin, S. N.; Gong, Q. F.; Li, Y. G.; Liu, Z. PEG-functionalized iron oxide nanoclusters loaded with chlorin e6 for targeted, NIR light induced, photodynamic therapy. Biomaterials 2013, 34, 9160–9170.Google Scholar
- [8]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
- [9]Hao, R.; Xing, R. J.; Xu, Z. C.; Hou, Y. L.; Gao, S.; Sun, S. H. Synthesis, functionalization, and biomedical applications of multifunctional magnetic nanoparticles. Adv. Mater. 2010, 22, 2729–2742.CrossRefGoogle Scholar
- [10]Liu, Z.; Tabakman, S.; Welsher, K.; Dai, H. J. Carbon nanotubes in biology and medicine: In vitro and in vivo detection, imaging and drug delivery. Nano Res. 2009, 2, 85–120.CrossRefGoogle Scholar
- [11]Yang, K.; Wan, J. M.; Zhang, S.; Tian, B.; Zhang, Y. J.; Liu, Z. The influence of surface chemistry and size of nanoscale graphene oxide on photothermal therapy of cancer using ultra-low laser power. Biomaterials 2012, 33, 2206–2214.CrossRefGoogle Scholar
- [12]Zhu, S. J.; Song, Y. B.; Zhao, X. H.; Shao, J. R.; Zhang, J. H.; Yang, B. The photoluminescence mechanism in carbon dots (graphene quantum dots, carbon nanodots, and polymer dots): Current state and future perspective. Nano Res. 2015, 8, 355–381.CrossRefGoogle Scholar
- [13]Vivero-Escoto, J. L.; Huxford-Phillips, R. C.; Lin, W. B. Silica-based nanoprobes for biomedical imaging and theranostic applications. Chem. Soc. Rev. 2012, 41, 2673–2685.CrossRefGoogle Scholar
- [14]Shen, J.; Song, G. S.; An, M.; Li, X. Q.; Wu, N.; Ruan, K. C.; Hu, J. Q.; Hu, R. G. The use of hollow mesoporous silica nanospheres to encapsulate bortezomib and improve efficacy for non-small cell lung cancer therapy. Biomaterials 2014, 35, 316–326.CrossRefGoogle Scholar
- [15]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
- [16]Nel, A.; Xia, T.; Mä dler, L.; Li, N. Toxic potential of materials at the nanolevel. Science 2006, 311, 622–627.CrossRefGoogle Scholar
- [17]Song, X. J.; Chen, Q.; Liu, Z. Recent advances in the development of organic photothermal nano-agents. Nano Res. 2015, 8, 340–354.CrossRefGoogle Scholar
- [18]Longmire, M.; Choyke, P. L.; Kobayashi, H. Clearance properties of nano-sized particles and molecules as imaging agents: Considerations and caveats. Nanomedicine 2008, 3, 703–717.CrossRefGoogle Scholar
- [19]Choi, H. S.; Liu, W. H.; Misra, P.; Tanaka, E.; Zimmer, J. P.; Ipe, B. I.; Bawendi, M. G.; Frangioni, J. V. Renal clearance of quantum dots. Nat. Biotechnol. 2007, 25, 1165–1170.CrossRefGoogle Scholar
- [20]Liu, J. B.; Yu, M. X.; Zhou, C.; Yang, S. Y.; Ning, X. H.; Zheng, J. Passive tumor targeting of renal-clearable luminescent gold nanoparticles: Long tumor retention and fast normal tissue clearance. J. Am. Chem. Soc. 2013, 135, 4978–4981.CrossRefGoogle Scholar
- [21]Tang, S. H.; Chen, M.; Zheng, N. F. Multifunctional ultrasmall Pd nanosheets for enhanced near-infrared photothermal therapy and chemotherapy of cancer. Nano Res. 2015, 8, 165–174.CrossRefGoogle Scholar
- [22]Huang, X.; Zeng, Z. Y.; Zhang, H. Metal dichalcogenide nanosheets: Preparation, properties and applications. Chem. Soc. Rev. 2013, 42, 1934–1946.CrossRefGoogle Scholar
- [23]Chen, Y.; Tan, C. L.; Zhang, H.; Wang, L. Z. Two-dimensional graphene analogues for biomedical applications. Chem. Soc. Rev. 2015, 44, 2681–2701.CrossRefGoogle Scholar
- [24]Zhang, H. Ultrathin two-dimensional nanomaterials. ACS Nano 2015, 9, 9451–9469.CrossRefGoogle Scholar
- [25]Tan, C. L.; Zhang, H. Two-dimensional transition metal dichalcogenide nanosheet-based composites. Chem. Soc. Rev. 2015, 44, 2713–2731.CrossRefGoogle Scholar
- [26]Liu, T.; Cheng, L.; Liu, Z. Two dimensional transitional metal dichalcogenides for biomedical applications. Acta Chim. Sinica 2015, 73, 902–912.CrossRefGoogle Scholar
- [27]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.CrossRefGoogle Scholar
- [28]Liu, Q.; Sun, C. Y.; He, Q.; Khalil, A.; Xiang, T.; Liu, D. B.; Zhou, Y.; Wang, J.; Song, L. Stable metallic 1T-WS2 ultrathin nanosheets as a promising agent for near-infrared photothermal ablation cancer therapy. Nano Res. 2015, 8, 3982–3991.CrossRefGoogle Scholar
- [29]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.CrossRefGoogle Scholar
- [30]Yin, W. Y.; Yan, L.; Yu, J.; Tian, G.; Zhou, L. J.; Zheng, X. P.; Zhang, X.; Yong, Y.; Li, J.; Gu, Z. J. et al. High-throughput synthesis of single-layer MoS2 nanosheets as a near-infrared photothermal-triggered drug delivery for effective cancer therapy. ACS Nano 2014, 8, 6922–6933.CrossRefGoogle Scholar
- [31]Li, J.; Jiang, F.; Yang, B.; Song, X.-R.; Liu, Y.; Yang, H.-H.; Cao, D.-R.; Shi, W.-R.; Chen, G.-N. Topological insulator bismuth selenide as a theranostic platform for simultaneous cancer imaging and therapy. Sci. Rep. 2013, 3, 1998.Google Scholar
- [32]Qian, X. X.; Shen, S. D.; Liu, T.; Cheng, L.; Liu, Z. Two-dimensional TiS2 nanosheets for in vivo photoacoustic imaging and photothermal cancer therapy. Nanoscale 2015, 7, 6380–6387.CrossRefGoogle Scholar
- [33]Liu, T.; Shi, S. X.; Liang, C.; Shen, S. D.; Cheng, L.; Wang, C.; Song, X. J.; Goel, S.; Barnhart, T. E.; Cai, W. B. 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.CrossRefGoogle Scholar
- [34]Yang, G. B.; Gong, H.; Liu, T.; Sun, X. Q.; Cheng, L.; Liu, Z. Two-dimensional magnetic WS2@Fe3O4 nanocomposite with mesoporous silica coating for drug delivery and imagingguided therapy of cancer. Biomaterials 2015, 60, 62–71.CrossRefGoogle Scholar
- [35]Cheng, L.; Shen, S. D.; Shi, S. X.; Yi, Y.; Wang, X. Y.; Song, G. S.; Yang, K.; Liu, G.; Barnhart, T. E.; Cai, W. B. et al. FeSe2-decorated Bi2Se3 nanosheets fabricated via cation exchange for chelator-free 64Cu-labeling and multimodal image-guided photothermal-radiation therapy. Adv. Funct. Mater. 2016, 26, 2185–2197.CrossRefGoogle Scholar
- [36]Cheng, L.; Yuan, C.; Shen, S. D.; Yi, X.; Gong, H.; Yang, K.; Liu, Z. Bottom-up synthesis of metal-ion-doped WS2 nanoflakes for cancer theranostics. ACS Nano 2015, 9, 11090–11101.CrossRefGoogle Scholar
- [37]Xu, S. J.; Li, D.; Wu, P. Y. One-pot, facile, and versatile synthesis of monolayer MoS2/WS2 quantum dots as bioimaging probes and efficient electrocatalysts for hydrogen evolution reaction. Adv. Funct. Mater. 2015, 25, 1127–1136.CrossRefGoogle Scholar
- [38]Wang, T. Y.; Zhu, H. C.; Zhuo, J. Q.; Zhu, Z. W.; Papakonstantinou, P.; Lubarsky, G.; Lin, J.; Li, M. X. Biosensor based on ultrasmall MoS2 nanoparticles for electrochemical detection of H2O2 released by cells at the nanomolar level. Anal. Chem. 2013, 85, 10289–10295.CrossRefGoogle Scholar
- [39]Yong, Y.; Cheng, X. J.; Bao, T.; Zu, M.; Yan, L.; Yin, W. Y.; Ge, C. C.; Wang, D. L.; Gu, Z. J.; Zhao, Y. L. Tungsten sulfide quantum dots as multifunctional nanotheranostics for in vivo dual-modal image-guided photothermal/radiotherapy synergistic therapy. ACS Nano 2015, 9, 12451–12463.CrossRefGoogle Scholar
- [40]Wang, X. W.; Sun, G. Z.; Li, N.; Chen, P. Quantum dots derived from two-dimensional materials and their applications for catalysis and energy. Chem. Soc. Rev. 2016, 45, 2239–2262.CrossRefGoogle Scholar
- [41]Zhang, X.; Lai, Z. C.; Liu, Z. D.; Tan, C. L.; Huang, Y.; Li, B.; Zhao, M. T.; Xie, L. H.; Huang, W.; Zhang, H. A facile and universal top-down method for preparation of monodisperse transition-metal dichalcogenide nanodots. Angew. Chem. 2015, 127, 5515–5518.CrossRefGoogle Scholar
- [42]Zhao, X.; Ma, X.; Sun, J.; Li, D. H.; Yang, X. R. Enhanced catalytic activities of surfactant-assisted exfoliated WS2 nanodots for hydrogen evolution. ACS Nano 2016, 10, 2159–2166.CrossRefGoogle Scholar
- [43]Zhang, X.-D.; Zhang, J. X.; Wang, J. Y.; Yang, J.; Chen, J.; Shen, X.; Deng, J.; Deng, D. H.; Long, W.; Sun, Y.-M. et al. Highly catalytic nanodots with renal clearance for radiation protection. ACS Nano 2016, 10, 4511–4519.CrossRefGoogle Scholar
- [44]Zong, X.; Na, Y.; Wen, F. Y.; Ma, G. J.; Yang, J. H.; Wang, D. G.; Ma, Y.; Wang, M.; Sun, L. C.; Li, C. Visible light driven H2 production in molecular systems employing colloidal MoS2 nanoparticles as catalyst. Chem. Commun. 2009, 4536–4538.Google Scholar
- [45]Lince, J. R.; Frantz, P. P. Anisotropic oxidation of MoS2 crystallites studied by angle-resolved X-ray photoelectron spectroscopy. Tribol. Lett. 2001, 9, 211–218.CrossRefGoogle Scholar
- [46]Gopalakrishnan, D.; Damien, D.; Shaijumon, M. M. MoS2 quantum dot-interspersed exfoliated MoS2 nanosheets. ACS Nano 2014, 8, 5297–5303.CrossRefGoogle Scholar
- [47]Baker, M. A.; Gilmore, R.; Lenardi, C.; Gissler, W. of S from MoS2 and determination of MoSx stoichiometry from Mo and S peak positions. Appl. Surf. Sci. 1999, 150, 255–262.Google Scholar
- [48]Stipp, S. L.; Hochella, M. F., Jr. Structure and bonding environments at the calcite surface as observed with X-ray photoelectron spectroscopy (XPS) and low energy electron diffraction (LEED). Geochim. Cosmochim. Ac. 1991, 55, 1723–1736.CrossRefGoogle Scholar
- [49]Zeng, Z. Y.; Yin, Z. Y.; Huang, X.; Li, H.; He, Q. Y.; Lu, G.; Boey, F.; Zhang, H. Single-layer semiconducting nanosheets: High-yield preparation and device fabrication. Angew. Chem., Int. Ed. 2011, 50, 11093–11097.CrossRefGoogle Scholar
- [50]Chou, S. S.; De, M.; Kim, J.; Byun, S.; Dykstra, C.; Yu, J.; Huang, J. X.; Dravid, V. P. Ligand conjugation of chemically exfoliated MoS2. J. Am. Chem. Soc. 2013, 135, 4584–4587.CrossRefGoogle Scholar
- [51]Li, S.-D.; Huang, L. Pharmacokinetics and biodistribution of nanoparticles. Mol. Pharm. 2008, 5, 496–504.CrossRefGoogle Scholar
- [52]Rosencwaig, A.; Gersho, A. Theory of the photoacoustic effect with solids. J. Appl. Phys. 1976, 47, 64–69.CrossRefGoogle Scholar
- [53]Gong, Q. F.; Cheng, L.; Liu, C. H.; Zhang, M.; Feng, Q. L.; Ye, H. L.; Zeng, M.; Xie, L. M.; Liu, Z.; Li, Y. G. Ultrathin MoS2(1–x)Se2x alloy nanoflakes for electrocatalytic hydrogen evolution reaction. ACS Catal. 2015, 5, 2213–2219.CrossRefGoogle Scholar
- [54]Cheng, L.; He, W. W.; Gong, H.; Wang, C.; Chen, Q.; Cheng, Z. P.; Liu, Z. PEGylated micelle nanoparticles encapsulating a non-fluorescent near-infrared organic dye as a safe and highly-effective photothermal agent for in vivo cancer therapy. Adv. Funct. Mater. 2013, 23, 5893–5902.CrossRefGoogle Scholar
