Skip to main content
SpringerLink
Log in

Ofloxacin loaded MoS2 nanoflakes for synergistic mild-temperature photothermal/antibiotic therapy with reduced drug resistance of bacteria

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Antibiotic resistance is an increasingly serious threat to global public health, which can lead to the decrease of the effectiveness of antibiotics. The combination therapy of antibiotic and mild temperature photothermal therapy (PTT) is adopted to address this issue in this work. An antibiotic-loaded nanoplatform is fabricated based on two-dimensional (2D) molybdenum disulfide (MoS2) nanoflakes as effective near-infrared (NIR) photothermal agent. The MoS2 nanoflakes is modified with positively charged quaternized chitosan (QCS) to improve the dispersion stability and enhance the interaction between MoS2 nanoflakes and bacterial membrane. The QCS modified MoS2 nanoflakes (QCS-MoS2) is expected to adhere onto the membrane of methicillin-resistant Staphylococcus aureus (MRSA) and depolarize the bacterial membrane by local hyperthermia under NIR irradiation. A first-line antibiotic, ofloxacin (OFLX), can be loaded onto QCS-MoS2 by π-π stacking and hydrophobic interaction. Due to the combined antibiotic-photothermal therapy, superior bactericidal ability was achieved at mild temperature (45 °C) and low antibiotic concentration. Such synergistic mild-temperature photothermal/antibiotic therapy can not only avoid the damage to neighboring tissue by PTT, but also reduce the development of drug resistance, providing an innovative way for the treatment of bacterial infections.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Levy, S. B.; Marshall, B. Antibacterial resistance worldwide: Causes, challenges and responses. Nat. Med.2004, 10, S122–S129.

    CAS  Google Scholar 

  2. Taubes, G. The bacteria fight back. Science2008, 321, 356–361.

    CAS  Google Scholar 

  3. Li, B. Y.; Webster, T. J. Bacteria antibiotic resistance: New challenges and opportunities for implant-associated orthopedic infections. J. Orthop. Res.2018, 36, 22–32.

    Google Scholar 

  4. Alanis, A. J. Resistance to antibiotics: Are we in the post-antibiotic era? Arch. Med. Res.2005, 36, 697–705.

    Google Scholar 

  5. Yang, X. L.; Zhang, L. M.; Jiang, X. Y. Aminosaccharide-gold nanoparticle assemblies as narrow-spectrum antibiotics against methicillin-resistant Staphylococcus aureus. Nano Res.2018, 11, 6237–6243.

    CAS  Google Scholar 

  6. Roy, I.; Shetty, D.; Hota, R.; Baek, K.; Kim, J.; Kim, C.; Kappert, S.; Kim, K. A Multifunctional subphthalocyanine nanosphere for targeting, labeling, and killing of antibiotic-resistant bacteria. Angew. Chem., Int. Ed.2015, 54, 15152–15155.

    CAS  Google Scholar 

  7. Hu, D. F.; Deng, Y. Y.; Jia, F.; Jin, Q.; Ji, J. Surface charge switchable supramolecular nanocarriers for nitric oxide synergistic photodynamic eradication of biofilms. ACS Nano2020, 14, 347–359.

    CAS  Google Scholar 

  8. Hu, X. N.; Zhao, Y. Y.; Hu, Z. J.; Saran, A.; Hou, S.; Wen, T.; Liu, W. Q.; Ji, Y. L.; Jiang, X. Y.; Wu, X. C. Gold nanorods core/AgPt alloy nanodots shell: A novel potent antibacterial nanostructure. Nano Res.2013, 6, 822–835.

    CAS  Google Scholar 

  9. Hu, D. F.; Li, H.; Wang, B. L.; Ye, Z.; Lei, W. X.; Jia, F.; Jin, Q.; Ren, K. F.; Ji, J. Surface-adaptive gold nanoparticles with effective adherence and enhanced photothermal ablation of methicillin-resistant Staphylococcus aureus biofilm. ACS Nano2017, 11, 9330–9339.

    CAS  Google Scholar 

  10. Yu, Q.; Chen, H. Smart antibacterial surfaces with switchable function to kill and release bacteria. Acta Polym. Sin.2020, 51, 319–325.

    Google Scholar 

  11. Wei, T.; Tang, Z. C.; Yu, Q.; Chen, H. Smart antibacterial surfaces with switchable bacteria-killing and bacteria-releasing capabilities. ACS Appl. Mater. Interfaces2017, 9, 37511–37523.

    CAS  Google Scholar 

  12. Li, J.; Liu, X. M.; Tan, L.; Cui, Z. D.; Yang, X. J.; Liang, Y. Q.; Li, Z. Y.; Zhu, S. L.; Zheng, Y. F.; Yeung, K. W. K. et al. Zinc-doped Prussian blue enhances photothermal clearance of Staphylococcus aureus and promotes tissue repair in infected wounds. Nat. Commun.2019, 10, 4490.

    Google Scholar 

  13. Gao, Y. F.; Wang, J.; Hu, D. F.; Deng, Y. Y.; Chen, T. T.; Jin, Q.; Ji, J. Bacteria-targeted supramolecular photosensitizer delivery vehicles for photodynamic ablation against biofilms. Macromol. Rapid Commun.2019, 40, 1800763.

    Google Scholar 

  14. Mao, C. Y.; Xiang, Y. M.; Liu, X. M.; Cui, Z. D.; Yang, X. J.; Li, Z. Y.; Zhu, S. L.; Zheng, Y. F.; Yeung, K. W. K.; Wu, S. L. Repeatable photodynamic therapy with triggered signaling pathways of fibroblast cell proliferation and differentiation to promote bacteria-accompanied wound healing. ACS Nano2018, 12, 1747–1759.

    CAS  Google Scholar 

  15. Yin, W. Y.; Yu, J.; Lv, F. T.; Yan, L.; Zheng, L. R.; Gu, Z. J.; Zhao, Y. L. Functionalized nano-MoS2 with peroxidase catalytic and near-infrared photothermal activities for safe and synergetic wound antibacterial applications. ACS Nano2016, 10, 11000–11011.

    CAS  Google Scholar 

  16. Korupalli, C.; Huang, C. C.; Lin, W. C.; Pan, W. Y.; Lin, P. Y.; Wan, W. L.; Li, M. J.; Chang, Y.; Sung, H. W. Acidity-triggered charge-convertible nanoparticles that can cause bacterium-specific aggregation in situ to enhance photothermal ablation of focal infection. Biomaterials2017, 116, 1–9.

    CAS  Google Scholar 

  17. Fan, X. L.; Li, H. Y.; Ye, W. Y.; Zhao, M. Q.; Huang, D. N.; Fang, Y.; Zhou, B. Q.; Ren, K. F.; Ji, J.; Fu, G. S. Magainin-modified polydopamine nanoparticles for photothermal killing of bacteria at low temperature. Colloids Surf. B.2019, 183, 110423.

    CAS  Google Scholar 

  18. Qu, Y. C.; Wei, T.; Zhao, J.; Jiang, S. B.; Yang, P.; Yu, Q.; Chen, H. Regenerable smart antibacterial surfaces: Full removal of killed bacteria via a sequential degradable layer. J. Mater. Chem. B2018, 6, 3946–3955.

    CAS  Google Scholar 

  19. Chen, J. Q.; Ning, C. Y.; Zhou, Z. N.; Yu, P.; Zhu, Y.; Tan, G. X.; Mao, C. B. Nanomaterials as photothermal therapeutic agents. Prog. Mater. Sci.2019, 99, 1–26

    Google Scholar 

  20. Gao, Q.; Zhang, X.; Yin, W. Y.; Ma, D. Q.; Xie, C. J.; Zheng, L. R.; Dong, X. H.; Mei, L. Q.; Yu, J.; Wang, C. Z. et al. Functionalized MoS2 nanovehicle with near-infrared laser-mediated nitric oxide release and photothermal activities for advanced bacteria-infected wound therapy. Small2018, 14, 1802290.

    Google Scholar 

  21. Hu, D. F.; Zou, L. Y.; Li, B. C.; Hu, M.; Ye, W. Y.; Ji, J. Photothermal killing of methicillin-resistant Staphylococcus aureus by bacteria-targeted polydopamine nanoparticles with nano-localized hyperpyrexia. ACS Biomater. Sci. Eng.2019, 5, 5169–5179.

    CAS  Google Scholar 

  22. Sun, P. P.; Zhang, Y.; Ran, X.; Liu, C. Y.; Wang, Z. Z.; Ren, J. S.; Qu, X. G. Phytochemical-encapsulated nanoplatform for “on-demand” synergistic treatment of multidrug-resistant bacteria. Nano Res.2018, 11, 3762–3770.

    CAS  Google Scholar 

  23. He, D. F.; Yang, T.; Qian, W.; Qi, C.; Mao, L.; Yu, X. Z.; Zhu, H. F.; Luo, G. X.; Deng, J. Combined photothermal and antibiotic therapy for bacterial infection via acidity-sensitive nanocarriers with enhanced antimicrobial performance. Appl. Mater. Today2018, 12, 415–429.

    Google Scholar 

  24. Tan, L.; Li, J.; Liu, X. M.; Cui, Z. D.; Yang, X. J.; Zhu, S. L.; Li, Z. Y.; Yuan, X. B.; Zheng, Y. F.; Yeung, K. W. K. et al. Rapid biofilm eradication on bone implants using red phosphorus and near-infrared light. Adv. Mater.2018, 30, 1801808.

    Google Scholar 

  25. Wei, T.; Yu, Q.; Chen, H. Responsive and synergistic antibacterial coatings: Fighting against bacteria in a smart and effective way. Adv. Healthcare Mater.2019, 8, 1801381.

    CAS  Google Scholar 

  26. Chen, M.; Chen, S. Z.; He, C. Y.; Mo, S. G.; Wang, X. Y.; Liu, G.; Zheng, N. F. Safety profile of two-dimensional Pd nanosheets for photothermal therapy and photoacoustic imaging. Nano Res.2017, 10, 1234–1248.

    CAS  Google Scholar 

  27. Zong, L. Y.; Wu, H. X.; Lin, H.; Chen, Y. A polyoxometalate-functionalized two-dimensional titanium carbide composite MXene for effective cancer theranostics. Nano Res.2018, 11, 4149–4168.

    CAS  Google Scholar 

  28. Bolotsky, A.; Butler, D.; Dong, C. Y.; Gerace, K.; Glavin, N. R.; Muratore, C.; Robinson, J. A.; Ebrahimi, A. Two-dimensional materials in biosensing and healthcare: From in vitro diagnostics to optogenetics and beyond. ACS Nano2019, 13, 9781–9810.

    CAS  Google Scholar 

  29. Tan, C. L.; Zhang, H. Two-dimensional transition metal dichalcogenide nanosheet-based composites. Chem. Soc. Rev.2015, 44, 2713–2731.

    CAS  Google Scholar 

  30. 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 Nano2015, 9, 950–960.

    CAS  Google Scholar 

  31. Feng, Z. Z.; Liu, X. M.; Tan, L.; Cui, Z. D.; Yang, X. J.; Li, Z. Y.; Zheng, Y. F.; Yeung, K. W. K.; Wu, S. L. Electrophoretic deposited stable chitosan@MoS2 coating with rapid in situ bacteria-killing ability under dual-light irradiation. Small2018, 14, 1704347.

    Google Scholar 

  32. 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 Nano2014, 8, 6922–6933.

    CAS  Google Scholar 

  33. Yadav, V.; Roy, S.; Singh, P.; Khan, Z.; Jaiswal, A. 2D MoS2-based nanomaterials for therapeutic, bioimaging, and biosensing applications. Small2019, 15, 1803706.

    Google Scholar 

  34. Zhu, X. B.; Ji, X. Y.; Kong, N.; Chen, Y. H.; Mahmoudi, M.; Xu, X. D.; Ding, L.; Tao, W.; Cai, T.; Li, Y. J. et al. Intracellular mechanistic understanding of 2D MoS2 nanosheets for anti-exocytosis-enhanced synergistic cancer therapy. ACS Nano2018, 12, 2922–2938.

    CAS  Google Scholar 

  35. Nicolosi, V.; Chhowalla, M.; Kanatzidis, M. G.; Strano, M. S.; Coleman, J. N. Liquid exfoliation of layered materials. Science2013, 340, 1226419.

    Google Scholar 

  36. Chai, M. Y.; Gao, Y. F.; Liu, J.; Deng, Y. Y.; Hu, D. F.; Jin, Q.; Ji, J. Polymyxin B-polysaccharide polyion nanocomplex with improved biocompatibility and unaffected antibacterial activity for acute lung infection management. Adv. Healthcare Mater.2020, 9, 1901542.

    CAS  Google Scholar 

  37. Yao, Q. Q.; Ye, Z.; Sun, L.; Jin, Y. Y.; Xu, Q. W.; Yang, M.; Wang, Y.; Zhou, Y. L.; Ji, J.; Chen, H. et al. Bacterial infection microenvironment-responsive enzymatically degradable multilayer films for multifunctional antibacterial properties. J. Mater. Chem. B2017, 5, 8532–8541.

    CAS  Google Scholar 

  38. 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.

    Google Scholar 

  39. Cho, J.; Grant, J.; Piquette-Miller, M.; Allen, C. Synthesis and physicochemical and dynamic mechanical properties of a water-soluble chitosan derivative as a biomaterial. Biomacromolecules2006, 7, 2845–2855.

    CAS  Google Scholar 

  40. Wang, J.; Zhuo, L. G.; Liao, W.; Yang, X.; Tang, Z. H.; Chen, Y.; Luo, S. Z.; Zhou, Z. J. Assessing the biocidal activity and investigating the mechanism of oligo-p-phenylene-ethynylenes. ACS Appl. Mater. Interfaces2017, 9, 7964–7971.

    CAS  Google Scholar 

  41. Zou, X. F.; Zhang, L.; Wang, Z. J.; Luo, Y. Mechanisms of the antimicrobial activities of graphene materials. J. Am. Chem. Soc.2016, 138, 2064–2077.

    CAS  Google Scholar 

  42. Yang, X.; Li, J.; Liang, T.; Ma, C. Y.; Zhang, Y. Y.; Chen, H. Z.; Hanagata, N.; Su, H. X.; Xu, M. S. Antibacterial activity of two-dimensional MoS2 sheets. Nanoscale2014, 6, 10126–10133.

    CAS  Google Scholar 

Download references

Acknowledgements

Financial support from the National Natural Science Foundation of China (No. 21774110) and Fundamental Research Funds for the Central Universities (Nos. 2019QNA4063 and 2019XZZX005-1-03) is gratefully acknowledged.

Author information

Author notes

  1. Yue Huang and Qiang Gao contributed equally to this work.

Authors and Affiliations

  1. MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China

    Yue Huang, Qiang Gao, Xu Li, Yifan Gao, Qiao Jin & Jian Ji

  2. Eye Center, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, China

    Haijie Han & Ke Yao

Authors
  1. Yue Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yifan Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haijie Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiao Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ke Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jian Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qiao Jin.

Electronic Supplementary Material

12274_2020_2853_MOESM1_ESM.pdf

Ofloxacin loaded MoS2 nanoflakes for synergistic mild-temperature photothermal/antibiotic therapy with reduced drug resistance of bacteria

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, Y., Gao, Q., Li, X. et al. Ofloxacin loaded MoS2 nanoflakes for synergistic mild-temperature photothermal/antibiotic therapy with reduced drug resistance of bacteria. Nano Res. 13, 2340–2350 (2020). https://doi.org/10.1007/s12274-020-2853-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-020-2853-2

Keywords

Search

Navigation