Journal Home > Volume 14 , Issue 11

Infectious diseases caused by bacteria are a global threat to the human health. Here, we propose a solvent "irrigation" technique to endow TiO2 nanotubes (NTs) to precisely modify with functional nanomaterials, and apply them in constructing a near-infrared (NIR) light controlled drug-delivery system for rapid necrosis of bacteria. In this design, the NIR stimuli-responsive functional shell is located on the external tube wall of TiO2 NT; the internal tube wall offers sufficient binding sites for drug loading. Using kanamycin as a model drug, we demonstrate that the reactive oxygen species generated in photocatalysis not only controllably release the loaded drug by scissoring the linked chains, but also effectively compromise bacteria membrane integrity by damaging the cell wall. Benefiting from the damages, antibiotics rapidly enter the bacteria and reach ≥99.9% reduction in Escherichia coli colony within only 2 h. Importantly, such a covalently conjugation-based delivery system can efficiently relieve radical-induced inflammation and cytotoxicity. This study provides an innovative design strategy for engineering delivery systems with tailorable components, enduring stimuli-response by multiple triggers.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

Engineering tailorable TiO2 nanotubes for NIR-controlled drug delivery

Show Author's information Yue Xu§Chenxi Zhao§Xi ZhangJingwen XuLingling YangZhechen ZhangZhida GaoYan-Yan Song( )
College of ScienceNortheastern UniversityShenyang 110004 China

§ Yue Xu and Chenxi Zhao contributed equally to this work.

Abstract

Infectious diseases caused by bacteria are a global threat to the human health. Here, we propose a solvent "irrigation" technique to endow TiO2 nanotubes (NTs) to precisely modify with functional nanomaterials, and apply them in constructing a near-infrared (NIR) light controlled drug-delivery system for rapid necrosis of bacteria. In this design, the NIR stimuli-responsive functional shell is located on the external tube wall of TiO2 NT; the internal tube wall offers sufficient binding sites for drug loading. Using kanamycin as a model drug, we demonstrate that the reactive oxygen species generated in photocatalysis not only controllably release the loaded drug by scissoring the linked chains, but also effectively compromise bacteria membrane integrity by damaging the cell wall. Benefiting from the damages, antibiotics rapidly enter the bacteria and reach ≥99.9% reduction in Escherichia coli colony within only 2 h. Importantly, such a covalently conjugation-based delivery system can efficiently relieve radical-induced inflammation and cytotoxicity. This study provides an innovative design strategy for engineering delivery systems with tailorable components, enduring stimuli-response by multiple triggers.

Keywords: photocatalysis, drug delivery, inflammatory response, near-infrared light, TiO2 naotubes, bacteria inactivation

References(61)

1

Morens, D. M.; Folkers G. K.; Fauci, A. S. The challenge of emerging and re-emerging infectious diseases. Nature 2004, 430, 242–249.

2

Cohen, M. Changing patterns of infectious disease. Nature 2000, 406, 762–767.

3

Alexander, J. W.; Good, R. A. Effect of antibiotics on the bactericidal activity of human leukocytes. J. Lab. Clin. Med. 1968, 71, 971–83.

4

Sang, Y. J.; Li, W.; Liu, H.; Zhang, L.; Wang, H.; Liu, Z. W.; Ren, J. S.; Qu, X. G. Construction of nanozyme-hydrogel for enhanced capture and elimination of bacteria. Adv. Funct. Mater. 2019, 29, 1900518.

5

Zhu, Y.; Xu, J.; Wang, Y. M.; Chen, C.; Gu, H. C.; Chai, Y. M.; Wang, Y. Silver nanoparticles-decorated and mesoporous silica coated single-walled carbon nanotubes with an enhanced antibacterial activity for killing drug-resistant bacteria. Nano Res. 2020, 13, 389–400.

6

Xu, J. W.; Zhou, X. M.; Gao, Z. D.; Song, Y. Y.; Schmuki, P. Visible- light-triggered drug release from TiO2 nanotube arrays: A controllable antibacterial platform. Angew. Chem., Int. Ed. 2016, 55, 593–597.

7

Huang, Y.; Gao, Q.; Li, X.; Gao, Y. F.; Han, H. J.; Jin, Q.; Yao, K.; Ji. J. Ofloxacin loaded MoS2 nanoflakes for synergistic mild-temperature photothermal/antibiotic therapy with reduced drug resistance of bacteria. Nano Res. 2020, 13, 2340–2350.

8

Mura, S.; Nicolas J.; Couvreur, P. Stimuli-responsive nanocarriers for drug delivery. Nat. Mater. 2013, 12, 991–1003.

9

Zwilling, V.; Aucouturier, M.; Darque-Ceretti, E. Anodic oxidation of titanium and TA6V alloy in chromic media. An electrochemical approach. Electrochim. Acta 1999, 45, 921–929.

10

Park, J.; Bauer, S.; von der Mark, K.; Schmuki, P. Nanosize and vitality: TiO2 nanotube diameter directs cell fate. Nano Lett. 2007, 7, 1686–1691.

11

Chen, X. B.; Mao, S. S. Titanium dioxide nanomaterials: Synthesis, properties, modifications, and applications. Chem. Rev. 2007, 107, 2891–2959.

12

Albu, S. P.; Ghicov, A.; Macak, J. M.; Hahn, R.; Schmuki, P. Self- organized, free-standing TiO2 nanotube membrane for flow-through photocatalytic applications. Nano Lett. 2007, 7, 1286–1289.

13

Song, Y. Y.; Schmidt-Stein, F.; Berger, S.; Schmuki, P. TiO2 nano test tubes as a self-cleaning platform for high-sensitivity immunoassays. Small 2010, 6, 1180–1184.

14

Xu, J. W.; Liu, N.; Wu, D.; Gao, Z. D.; Song, Y. Y.; Schmuki, P. Upconversion nanoparticle-assisted payload delivery from TiO2 under near-infrared light irradiation for bacterial inactivation. ACS Nano 2020, 14, 337−346.

15

Song, Y. Y.; Schmidt-Stein, F.; Bauer, S.; Schmuki, P. Amphiphilic TiO2 nanotube arrays: An actively controllable drug delivery system. J. Am. Chem. Soc. 2009, 131, 4230–4232.

16

Nosaka, Y.; Nosaka, A. Y. Generation and detection of reactive oxygen species in photocatalysis. Chem. Rev. 2017, 117, 11302–11336.

17

Liu, K. S.; Cao, M. Y.; Fujishima, A.; Jiang, L. Bio-inspired titanium dioxide materials with special wettability and their applications. Chem. Rev. 2014, 114, 10044–10094.

18

Garcia, J. V.; Yang, J. P.; Shen, D. K.; Yao, C.; Li, X. M.; Wang, R.; Stucky, G. D.; Zhao, D. Y.; Ford, P. C.; Zhang, F. NIR-triggered release of caged nitric oxide using upconverting nanostructured materials. Small 2012, 8, 3800–3805.

19

König, K. Multiphoton microscopy in life sciences. J. Microsc. 2000, 200, 83–104.

20

Wilson, B. C.; Jeeves W. P.; Lowe, D. M. In vivo and post mortem measurements of the attenuation spectra of light in mammalian tissues. Photochem. Photobiol. 1985, 42, 153–162.

21

Skirtach, A. G.; Javier, A. M.; Kreft, O.; Köhler, K.; Alberola, A. P.; Möhwald, H.; Parak, W. J.; Sukhorukov, G. B. Laser-induced release of encapsulated materials inside living cells. Angew. Chem., Int. Ed. 2006, 45, 4612–4617.

22

Palankar, R.; Pinchasik, B. E.; Khlebtsov, B. N.; Kolesnikova, T. A.; Möhwald, H.; Winterhalter, M.; Skirtach, A. G. Nanoplasmonically- induced defects in lipid membrane monitored by ion current: Transient nanopores versus membrane rupture. Nano Lett. 2014, 14, 4273–4279.

23

Delcea, M.; Sternberg, N.; Yashchenok, A. M.; Georgieva, R.; Bäumler, H.; Möhwald, H.; Skirtach, A. G. Nanoplasmonics for dual-molecule release through nanopores in the membrane of red blood cells. ACS Nano 2012, 6, 4169–4180.

24

Zhou, L.; Fan, Y.; Wang, R.; Li, X. M.; Fan, L. L.; Zhang, F. High- capacity upconversion wavelength and lifetime binary encoding for multiplexed biodetection. Angew. Chem., Int. Ed. 2018, 57, 12824– 12829.

25

Wang, P. Y.; Wang, C. L.; Lu, L. F.; Li, X. M.; Wang, W. X.; Zhao, M. Y.; Hu, L. D.; El-Toni, A. M.; Li, Q.; Zhang, F. Kinetics-mediate fabrication of multi-model bioimaging lanthanide nanoplates with controllable surface roughness for blood brain barrier transportation. Biomaterials 2017, 141, 223–232.

26

Ke, J. X.; Lu, S.; Li, Z.; Shang, X. Y.; Li, X. J.; Li, R. F.; Tu, D. T.; Chen, Z.; Chen, X. Y. Multiplexed intracellular detection based on dual-excitation/dual-emission upconversion nanoprobes. Nano Res. 2020, 13, 1955–1961.

27

Zhang, Z.; Jayakumar, M. K. G.; Zheng, X.; Shikha, S.; Zhang, Y.; Bansal, A.; Poon, D. J. J.; Chu, P. L.; Yeo, E. L. L.; Chua, M. L. K. et al. Upconversion superballs for programmable photoactivation of therapeutics. Nat. Commun. 2019, 10, 4586.

28

Tian, R. S.; Sun, W.; Li, M. L.; Long, S. R.; Li, M.; Fan, J. L.; Guo, L. Y.; Peng, X. J. Development of a novel anti-tumor theranostic platform: A near-infrared molecular upconversion sensitizer for deep-seated cancer photodynamic therapy. Chem. Sci. 2019, 10, 10106–10112.

29

Deng, R. R.; Qin, F.; Chen, R. F.; Huang, W.; Hong, M. H.; Liu, X. G. Temporal full-colour tuning through non-steady-state upconversion. Nat. Nanotechnol. 2015, 10, 237−242.

30

Ke, J. X.; Lu, S.; Li, Z.; Shang, X. Y.; Li, X. J.; Li, R. F.; Tu, D. T.; Chen, Z.; Chen, X. Y. Multiplexed intracellular detection based on dual-excitation/dual-emission upconversion nanoprobes. Nano Res. 2020, 13, 1955–1961.

31

Idris, N. M.; Gnanasammandhan, M. K.; Zhang, J.; Ho, P. C.; Mahendran, R.; Zhang, Y. In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers. Nat. Med. 2012, 18, 1580−1585.

32

Xu, Z. Z.; Quintanilla, M.; Vetrone, F.; Govorov, A. O.; Chaker, M.; Ma, D. L. Harvesting lost photons: Plasmon and upconversion enhanced broadband photocatalytic activity in core@shell microspheres based on lanthanide-doped NaYF4, TiO2, and Au. Adv. Funct. Mater. 2015, 25, 2950–2960.

33

Xu, X.; Sun, Y. F.; Zhang, Q. Y.; Cai, H. X.; Li, Q.; Zhou, S. Y. Synthesis and photocatalytic activity of plasmon-enhanced core-shell upconversion luminescent photocatalytic Ag@SiO2@YF3: Ho3+@TiO2 nanocomposites. Opt. Mater. 2019, 94, 444–453.

34

Zhou, Y.; Wu, S. J.; Wang, F.; Li, Q.; He, C. X.; Duan, N.; Wang, Z. P. Assessing the toxicity in vitro of degradation products from deoxynivalenol photocatalytic degradation by using upconversion nanoparticles@TiO2 composite. Chemosphere 2020, 238, 124648.

35

Zhang, F.; Wan, Y.; Yu, T.; Zhang, F. Q.; Shi, Y. F.; Xie, S. H.; Li, Y. G.; Xu, L.; Tu, B.; Zhao, D. Y. Uniform nanostructured arrays of sodium rare-earth fluorides for highly efficient multicolor upconversion luminescence. Angew. Chem., Int. Ed. 2007, 46, 7976–7979.

36

Tille, J.; Berlin, P.; Klemm, D. A novel efficient enzyme-immobilization reaction on NH2 polymers by means of L-ascorbic acid. Biotechnol. Appl. Biochem. 1999, 30, 155–162.

37

Zhang, T. S.; Ying, D.; Qi, M. L.; Li, X.; Fu, L.; Sun, X. L.; Wang, L.; Zhou, Y. M. Anti-biofilm property of bioactive upconversion nanocomposites containing chlorin e6 against periodontal pathogens. Molecules 2019, 24, 2692.

38

Ishibashi, K. I.; Fujishima, A.; Watanabe, T.; Hashimoto, K. Quantum yields of active oxidative species formed on TiO2 photocatalyst. J. Photochem. Photobiol. A 2000, 134, 139–142.

39

Younis, M. R.; Wang, C.; An, R. B.; Wang, S. J.; Younis, M. A.; Li, Z. Q.; Wang, Y.; Ihsan, A.; Ye, D. J.; Xia, X. H. Low power single laser activated synergistic cancer phototherapy using photosensitizer functionalized dual plasmonic photothermal nanoagents. ACS Nano 2019, 13, 2544–2557.

40

Eadie, M. J.; Tyrer, J. H.; Kukums, J. R.; Hooper, W. D. Aspects of tetrazolium salt reduction relevant to quantitative histochemistry. Histochemie 1970, 21, 170–180.

41

Nguyen, N. T.; Ozkan, S.; Hwang, I.; Mazare, A.; Schmuki, P. TiO2 nanotubes with laterally spaced ordering enable optimized hierarchical structures with significantly enhanced photocatalytic H2 generation. Nanoscale 2016, 8, 16868–16873.

42

Paramasivam, I.; Macak, J. M.; Schmuki, P. Photocatalytic activity of TiO2 nanotube layers loaded with Ag and Au nanoparticles. Electrochem. Commun. 2008, 10, 71–75.

43

Zhang, N.; Qi, M. Y.; Yuan, L.; Fu, X. Z.; Tang, Z. R.; Gong, J. L.; Xu, Y. J. Broadband light harvesting and unidirectional electron flow for efficient electron accumulation for hydrogen generation. Angew. Chem., Int. Ed. 2019, 58, 10003–10007.

44

Kubelka, P.; Munk, F. Reflection characteristics of paints. Z. Tech. Phys. 1931, 12, 593–601.

45

Gal, D.; Mastai, Y.; Hodes, G.; Kronik, L. Band gap determination of semiconductor powders via surface photovoltage spectroscopy. J. Appl. Phys. 1999, 86, 5573–5577.

46

Stouwdam, J. W.; Van Veggel, F. C. J. M. Near-infrared emission of redispersible Er3+, Nd3+, and Ho3+ Doped LaF3 nanoparticles. Nano Lett. 2002, 2, 733–737.

47

Menyuk, N.; Dwight, K.; Pierce, J. W. NaYF4: Yb, Er—an efficient upconversion phosphor. Appl. Phys. Lett. 1972, 21, 159–161.

48

Zou, W. Q.; Visser, C.; Maduro, J. A.; Pshenichnikov, M. S.; Hummelen, J. C. Broadband dye-sensitized upconversion of near-infrared light. Nat. Photonics 2012, 6, 560–564.

49

Zhang, N.; Han, C.; Xu, Y. J.; Foley Ⅳ, J. J.; Zhang, D. T.; Codrington, J.; Gray, S. K.; Sun, Y. G. Near-field dielectric scattering promotes optical absorption by platinum nanoparticles. Nature Photonics 2016, 10, 473–483.

50

Shiraishi, Y.; Sakamoto, H.; Fujiwara, K.; Ichikawa, S.; Hirai, T. Selective photocatalytic oxidation of aniline to nitrosobenzene by Pt nanoparticles supported on TiO2 under visible light irradiation. ACS Catal. 2014, 4, 2418−2425.

51

Schottky, W. Z. Zur halbleitertheorie der sperrschicht-und spitzengleichrichter. Z. Phys. 1939, 113, 367–414.

52

Shrestha, N. K.; Macak, J. M.; Schmidt-Stein, F.; Hahn, R.; Mierke, C. T.; Fabry, B.; Schmuki, P. Magnetically guided Titania nanotubes for site-selective photocatalysis and drug release. Angew. Chem., Int. Ed. 2009, 48, 969–972.

53

Ruhemann, S. CCXII. —Triketohydrindene hydrate. J. Chem. Soc., Trans. 1910, 97, 2025–2031.

54

Chong, A. S. M.; Zhao, X. S. Functionalization of SBA-15 with APTES and characterization of functionalized materials. J. Phys. Chem. B 2003, 107, 12650–12657.

55

Song, H.; Nor, Y. A.; Yu, M. H.; Yang, Y. N.; Zhang, J.; Zhang, H. W.; Xu, C.; Mitter, N.; Yu, C. Z. Silica nanopollens enhance adhesion for long-term bacterial inhibition. J. Am. Chem. Soc. 2016, 138, 6455–6462.

56

Liu, L. Z.; Chen, S.; Xue, Z. J.; Zhang, Z.; Qiao, X. Z.; Nie, Z. X.; Han, D.; Wang, J. L.; Wang, T. Bacterial capture efficiency in fluid bloodstream improved by bendable nanowires. Nat. Commun. 2018, 9, 444.

57

Cao, F. F.; Zhang, L.; Wang, H.; You, Y. W.; Wang, Y.; Gao, N.; Ren, J. S.; Qu, X. G. Defect-rich adhesive nanozymes as efficient antibiotics for enhanced bacterial inhibition. Angew. Chem., Int. Ed. 2019, 58, 16236–16242.

58

Xu, J. W.; Wu, D.; Li, Y. Z.; Xu, J.; Gao, Z. D.; Song, Y. Y. Plasmon- triggered hot-spot excitation on SERS substrates for bacterial inactivation and in situ monitoring. ACS Appl. Mater. Interfaces 2018, 10, 25219–25227.

59

Applerot, G.; Lipovsky, A.; Dror, R.; Perkas, N.; Nitzan, Y.; Lubart, R. Gedanken, A. Enhanced antibacterial activity of nanocrystalline ZnO due to increased ROS-mediated cell injury. Adv. Funct. Mater. 2009, 19, 842–852.

60

Williams, S. C.; Verity, P. G.; Beatty, T. A new staining technique for dual identification of plankton and detritus in seawater. J. Plankton Res. 1995, 17, 2037–2047.

61

Misba, L.; Zaidi, S.; Khan, A. U. Efficacy of photodynamic therapy against Streptococcus mutans biofilm: Role of singlet oxygen. J. Photochem. Photobiol. B 2018, 183, 16–21.

File
12274_2021_3338_MOESM1_ESM.pdf (3.2 MB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 24 November 2020
Revised: 12 January 2021
Accepted: 15 January 2021
Published: 10 February 2021
Issue date: November 2021

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2021

Acknowledgements

Acknowledgements

This research is supported by the National Natural Science Foundation of China (Nos. 21874013, 22074013, and 21775016) and the Research Funds for the Central Universities (Nos. N182410008-1 and N2005027), and the Talent Project of Revi- talizing Liaoning (No. XLYC1807165). Special thanks are due to the instrumental or data analysis from Analytical and Testing Center, Northeastern University.

Return