Biofilm Microenvironment-Responsive Nanotheranostics for Dual-Mode Imaging and Hypoxia-Relief-Enhanced Photodynamic Therapy of Bacterial Infections

Research - Tập 2020 - 2020
Weijun Xiu1, Siyu Gan1, Qirui Wen1, Qiu Qiu1, Sulai Dai1, Heng Dong2, Qiang Li2, Lihui Yuwen1, Lixing Weng3, Zhaogang Teng4, Yongbin Mou2, Lianhui Wang1
1Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Centre for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications, Nanjing 210023, China
2Department of Oral Implantology, Nanjing Stomatological Hospital, School of Medicine, Nanjing University, Nanjing 210023, China
3School of Geography and Biological Information, Nanjing University of Posts and Telecommunications, Nanjing, 210023, China
4Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China

Tóm tắt

The formation of bacterial biofilms closely associates with infectious diseases. Until now, precise diagnosis and effective treatment of bacterial biofilm infections are still in great need. Herein, a novel multifunctional theranostic nanoplatform based on MnO 2 nanosheets (MnO 2 NSs) has been designed to achieve pH-responsive dual-mode imaging and hypoxia-relief-enhanced antimicrobial photodynamic therapy (aPDT) of bacterial biofilm infections. In this study, MnO 2 NSs were modified with bovine serum albumin (BSA) and polyethylene glycol (PEG) and then loaded with chlorin e6 (Ce6) as photosensitizer to form MnO 2 -BSA/PEG-Ce6 nanosheets (MBP-Ce6 NSs). After being delivered into the bacterial biofilm-infected tissues, the MBP-Ce6 NSs could be decomposed in acidic biofilm microenvironment and release Ce6 with Mn 2+ , which subsequently activate both fluorescence (FL) and magnetic resonance (MR) signals for effective dual-mode FL/MR imaging of bacterial biofilm infections. Meanwhile, MnO 2 could catalyze the decomposing of H 2 O 2 in biofilm-infected tissues into O 2 and relieve the hypoxic condition of biofilm, which significantly enhances the efficacy of aPDT. An in vitro study showed that MBP-Ce6 NSs could significantly reduce the number of methicillin-resistant S taphylococcus aureus (MRSA) in biofilms after 635 nm laser irradiation. Guided by FL/MR imaging, MRSA biofilm-infected mice can be efficiently treated by MBP-Ce6 NSs-based aPDT. Overall, MBP-Ce6 NSs not only possess biofilm microenvironment-responsive dual-mode FL/MR imaging ability but also have significantly enhanced aPDT efficacy by relieving the hypoxia habitat of biofilm, which provides a promising theranostic nanoplatform for bacterial biofilm infections.

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Tài liệu tham khảo

L. Hall-Stoodley, J. W. Costerton, and P. Stoodley, “Bacterial biofilms: from the natural environment to infectious diseases,” Nature Reviews Microbiology, vol. 2, no. 2, pp. 95–108, 2004

10.1002/anie.201605296

D. Davies, “Understanding biofilm resistance to antibacterial agents,” Nature Reviews Drug Discovery, vol. 2, no. 2, pp. 114–122, 2003

Q. Deng, P. Sun, L. Zhang, Z. Liu, H. Wang, J. Ren, and X. Qu, “Porphyrin MOF dots–based, function-adaptive nanoplatform for enhanced penetration and photodynamic eradication of bacterial biofilms,” Advanced Functional Materials, vol. 29, no. 30, article 1903018, 2019

10.1038/nrmicro1557

10.1038/nrmicro.2016.94

H. Wu, C. Moser, H. Z. Wang, N. Høiby, and Z. J. Song, “Strategies for combating bacterial biofilm infections,” International Journal of Oral Science, vol. 7, no. 1, pp. 1–7, 2015

10.1038/nature12790

10.3390/molecules20045286

G. Fang, W. Li, X. Shen, J. M. Perez-Aguilar, Y. Chong, X. Gao, Z. Chai, C. Chen, C. Ge, and R. Zhou, “Differential Pd-nanocrystal facets demonstrate distinct antibacterial activity against Gram-positive and Gram-negative bacteria,” Nature Communications, vol. 9, no. 1, article 129, 2018

10.1002/anie.201408533

D. K. Kang, M. M. Ali, K. Zhang, S. S. Huang, E. Peterson, M. A. Digman, E. Gratton, and W. Zhao, “Rapid detection of single bacteria in unprocessed blood using integrated comprehensive droplet digital detection,” Nature Communications, vol. 5, no. 1, article 5427, 2014

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA, vol. 296, no. 2, pp. 202–211, 2006

M. K. S. Larsen, T. R. Thomsen, C. Moser, N. Høiby, and P. H. Nielsen, “Use of cultivation-dependent and -independent techniques to assess contamination of central venous catheters: a pilot study,” BMC Clinical Pathology, vol. 8, no. 1, p. 10, 2008

J. Tang, B. Chu, J. Wang, B. Song, Y. Su, H. Wang, and Y. He, “Multifunctional nanoagents for ultrasensitive imaging and photoactive killing of Gram-negative and Gram-positive bacteria,” Nature Communications, vol. 10, no. 1, article 4057, 2019

Z. Zhao, R. Yan, X. Yi, J. Li, J. Rao, Z. Guo, Y. Yang, W. Li, Y. Q. Li, and C. Chen, “Bacteria-activated theranostic nanoprobes against methicillin-resistant Staphylococcus aureus infection,” ACS Nano, vol. 11, no. 5, pp. 4428–4438, 2017

10.1038/nmat3074

M. van Oosten, T. Schäfer, J. A. C. Gazendam, K. Ohlsen, E. Tsompanidou, M. C. de Goffau, H. J. M. Harmsen, L. M. A. Crane, E. Lim, K. P. Francis, L. Cheung, M. Olive, V. Ntziachristos, J. M. van Dijl, and G. M. van Dam, “Real-time in vivo imaging of invasive- and biomaterial-associated bacterial infections using fluorescently labelled vancomycin,” Nature Communications, vol. 4, no. 1, article 2584, 2013

10.1021/jacs.8b03304

Z. Zhao, H. Fan, G. Zhou, H. Bai, H. Liang, R. Wang, X. Zhang, and W. Tan, “Activatable fluorescence/MRI bimodal platform for tumor cell imaging via MnO2 nanosheet–aptamer nanoprobe,” Journal of the American Chemical Society, vol. 136, no. 32, pp. 11220–11223, 2014

S. Zhu, R. Tian, A. L. Antaris, X. Chen, and H. Dai, “Near-infrared-II molecular dyes for cancer imaging and surgery,” Advanced Materials, vol. 31, no. 24, article 1900321, 2019

10.1021/cr100025t

X. Pang, X. Liu, Y. Cheng, C. Zhang, E. Ren, C. Liu, Y. Zhang, J. Zhu, X. Chen, and G. Liu, “Sono-immunotherapeutic nanocapturer to combat multidrug-resistant bacterial infections,” Advanced Materials, vol. 31, no. 35, article 1902530, 2019

A. Gupta, R. Das, G. Yesilbag Tonga, T. Mizuhara, and V. M. Rotello, “Charge-switchable nanozymes for bioorthogonal imaging of biofilm-associated infections,” ACS Nano, vol. 12, no. 1, pp. 89–94, 2018

T. F. Moriarty, J. S. Elborn, and M. M. Tunney, “Effect of pH on the antimicrobial susceptibility of planktonic and biofilm-grown clinical Pseudomonas aeruginosa isolates,” British Journal of Biomedical Science, vol. 64, no. 3, pp. 101–104, 2007

P. O. Jensen, M. Kolpen, K. N. Kragh, and M. Kuhl, “Microenvironmental characteristics and physiology of biofilms in chronic infections of CF patients are strongly affected by the host immune response,” APMIS, vol. 125, no. 4, pp. 276–288, 2017

Y. Liu, Z. Ren, G. Hwang, and H. Koo, “Therapeutic strategies targeting cariogenic biofilm microenvironment,” Advances in Dental Research, vol. 29, no. 1, pp. 86–92, 2018

D. Mao, F. Hu, Kenry, S. Ji, W. Wu, D. Ding, D. Kong, and B. Liu, “Metal-organic-framework-assisted in vivo bacterial metabolic labeling and precise antibacterial therapy,” Advanced Materials, vol. 30, no. 18, article 1706831, 2018

D. S. Benoit, and H. Koo, “Targeted, triggered drug delivery to tumor and biofilm microenvironments,” Nanomedicine, vol. 11, no. 8, pp. 873–879, 2016

D. S. W. Benoit, K. R. Sims Jr., and D. Fraser, “Nanoparticles for oral biofilm treatments,” ACS Nano, vol. 13, no. 5, pp. 4869–4875, 2019

Z. Xu, Z. Qiu, Q. Liu, Y. Huang, D. Li, X. Shen, K. Fan, J. Xi, Y. Gu, Y. Tang, J. Jiang, J. Xu, J. He, X. Gao, Y. Liu, H. Koo, X. Yan, and L. Gao, “Converting organosulfur compounds to inorganic polysulfides against resistant bacterial infections,” Nature Communications, vol. 9, no. 1, article 3713, 2018

Y. Liu, H. C. van der Mei, B. Zhao, Y. Zhai, T. Cheng, Y. Li, Z. Zhang, H. J. Busscher, Y. Ren, and L. Shi, “Eradication of Multidrug-Resistant Staphylococcal Infections by light-activatable micellar nanocarriers in a murine model,” Advanced Functional Materials, vol. 27, no. 44, article 1701974, 2017

D. Hu, H. Li, B. Wang, Z. Ye, W. Lei, F. Jia, Q. Jin, K. F. Ren, and J. Ji, “Surface-adaptive gold nanoparticles with effective adherence and enhanced photothermal ablation of methicillin-resistant Staphylococcus aureus biofilm,” ACS Nano, vol. 11, no. 9, pp. 9330–9339, 2017

H. Zhu, Y. Fang, Q. Miao, X. Qi, D. Ding, P. Chen, and K. Pu, “Regulating near-infrared photodynamic properties of semiconducting polymer nanotheranostics for optimized cancer therapy,” ACS Nano, vol. 11, no. 9, pp. 8998–9009, 2017

H. Zhu, J. Li, X. Qi, P. Chen, and K. Pu, “Oxygenic Hybrid semiconducting nanoparticles for enhanced photodynamic therapy,” Nano Letters, vol. 18, no. 1, pp. 586–594, 2018

D. Xu, C. Zhou, C. Zhan, Y. Wang, Y. You, X. Pan, J. Jiao, R. Zhang, Z. Dong, W. Wang, and X. Ma, “Enzymatic micromotors as a mobile photosensitizer platform for highly efficient on-chip targeted antibacteria photodynamic therapy,” Advanced Functional Materials, vol. 29, no. 17, article 1807727, 2019

K. Kai, Y. Yoshida, H. Kageyama, G. Saito, T. Ishigaki, Y. Furukawa, and J. Kawamata, “Room-temperature synthesis of manganese oxide monosheets,” Journal of the American Chemical Society, vol. 130, no. 47, pp. 15938–15943, 2008

Y. Chen, D. Ye, M. Wu, H. Chen, L. Zhang, J. Shi, and L. Wang, “Break-up of two-dimensional MnO2 nanosheets promotes ultrasensitive pH-triggered theranostics of cancer,” Advanced Materials, vol. 26, no. 41, pp. 7019–7026, 2014

D. He, X. He, K. Wang, X. Yang, X. Yang, Z. Zou, and X. Li, “Redox-responsive degradable honeycomb manganese oxide nanostructures as effective nanocarriers for intracellular glutathione-triggered drug release,” Chemical Communications, vol. 51, no. 4, pp. 776–779, 2015

Y. Zhang, W. Xiu, Y. Sun, D. Zhu, Q. Zhang, L. Yuwen, L. Weng, Z. Teng, and L. Wang, “RGD-QD-MoS2 nanosheets for targeted fluorescent imaging and photothermal therapy of cancer,” Nanoscale, vol. 9, no. 41, pp. 15835–15845, 2017

10.1039/C6TB01988A

Q. Chen, L. Feng, J. Liu, W. Zhu, Z. Dong, Y. Wu, and Z. Liu, “Intelligent Albumin-MnO2 Nanoparticles as pH-/H2O2-Responsive dissociable nanocarriers to modulate tumor hypoxia for effective combination therapy,” Advanced Materials, vol. 28, no. 33, pp. 7129–7136, 2016

10.1002/adma.201405141

S. Lin, H. Cheng, Q. Ouyang, and H. Wei, “Deciphering the quenching mechanism of 2D MnO2 nanosheets towards Au nanocluster fluorescence to design effective glutathione biosensors,” Analytical Methods, vol. 8, no. 19, pp. 3935–3940, 2016

G. Yang, L. Xu, Y. Chao, J. Xu, X. Sun, Y. Wu, R. Peng, and Z. Liu, “Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses,” Nature Communications, vol. 8, no. 1, article 902, 2017

X. Wang, D. Niu, Q. Wu, S. Bao, T. Su, X. Liu, S. Zhang, and Q. Wang, “Iron oxide/manganese oxide co-loaded hybrid nanogels as pH-responsive magnetic resonance contrast agents,” Biomaterials, vol. 53, pp. 349–357, 2015

10.1038/nrmicro1838

10.1016/j.tibtech.2018.10.011

K. Mathee, O. Ciofu, C. Sternberg, P. W. Lindum, J. I. A. Campbell, P. Jensen, A. H. Johnsen, M. Givskov, D. E. Ohman, M. Søren, N. Høiby, and A. Kharazmi, “Mucoid conversion of Pseudomonas aeruginos by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung,” Microbiology, vol. 145, no. 6, pp. 1349–1357, 1999

10.1038/nri3423

Q. Chen, C. Liang, X. Sun, J. Chen, Z. Yang, H. Zhao, L. Feng, and Z. Liu, “H2O2-responsive liposomal nanoprobe for photoacoustic inflammation imaging and tumor theranostics via in vivo chromogenic assay,” Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 21, pp. 5343–5348, 2017

J. X. Fan, M. Y. Peng, H. Wang, H. R. Zheng, Z. L. Liu, C. X. Li, X. N. Wang, X. H. Liu, S. X. Cheng, and X. Z. Zhang, “Engineered bacterial bioreactor for tumor therapy via Fenton-like reaction with localized H2O2 Generation,” Advanced Materials, vol. 31, no. 16, article 1808278, 2019

Y. Jiang, J. Li, Z. Zeng, C. Xie, Y. Lyu, and K. Pu, “Organic photodynamic nanoinhibitor for synergistic cancer therapy,” Angewandte Chemie International Edition, vol. 58, no. 24, pp. 8161–8165, 2019

Q. Miao, and K. Pu, “Organic semiconducting agents for deep-tissue molecular imaging: second near-infrared fluorescence, self-luminescence, and photoacoustics,” Advanced Materials, vol. 30, no. 49, article 1801778, 2018

S. L. Percival, K. E. Hill, D. W. Williams, S. J. Hooper, D. W. Thomas, and J. W. Costerton, “A review of the scientific evidence for biofilms in wounds,” Wound Repair and Regeneration, vol. 20, no. 5, pp. 647–657, 2012

G. Nakagami, G. Schultz, D. J. Gibson, P. Phillips, A. Kitamura, T. Minematsu, T. Miyagaki, A. Hayashi, S. Sasaki, J. Sugama, and H. Sanada, “Biofilm detection by wound blotting can predict slough development in pressure ulcers: a prospective observational study,” Wound Repair and Regeneration, vol. 25, no. 1, pp. 131–138, 2017

M. Sønderholm, T. Bjarnsholt, M. Alhede, M. Kolpen, P. Jensen, M. Kühl, and K. Kragh, “The consequences of being in an infectious biofilm: microenvironmental conditions governing antibiotic tolerance,” International Journal of Molecular Sciences, vol. 18, no. 12, pp. 2688–2701, 2017

Z. Wang, Y. Zhang, E. Ju, Z. Liu, F. Cao, Z. Chen, J. Ren, and X. Qu, “Biomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumors,” Nature Communications, vol. 9, no. 1, article 3334, 2018

J. Hao, G. Song, T. Liu, X. Yi, K. Yang, L. Cheng, and Z. Liu, “In Vivo long-term biodistribution, excretion, and toxicology of PEGylated transition-metal dichalcogenides MS2 (M = Mo, W, Ti) nanosheets,” Advanced Science, vol. 4, no. 1, article 1600160, 2017