AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Nano Research Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article

Fluorescent silicon nanoparticles-based nanotheranostic agents for rapid diagnosis and treatment of bacteria-induced keratitis

Lu Zhang1,§, Xiaoyuan Ji1,§, Yuanyuan Su1( ), Xia Zhai1, Hua Xu2, Bin Song1, Airui Jiang1, Daoxia Guo1, Yao He1( )
Laboratory of Nanoscale Biochemical Analysis, Institute of Functional Nano and Soft Materials (FUNSOM), and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China
Department of Ophthalmology, Children’s Hospital of Soochow University, Soochow University, Suzhou 215123, China

§ Lu Zhang and Xiaoyuan Ji contributed equally to this work.

Show Author Information

Graphical Abstract

Abstract

Recommended as a medical emergency, infectious keratitis with an acute and rapid disease progression can lead to serious damage of vision and even blindness. Herein, we present a kind of theranostic agents, which are made of vancomycin (Van)-modified fluorescent silicon nanoparticles (SiNPs-Van), enabling rapid and non-invasive diagnosis and treatment of Gram-positive bacteria-induced keratitis in a simultaneous manner. Typically, the resultant SiNPs-Van nanoagents have an ability of imaging bacteria in a short time both in vitro (5 min) and in vivo (10 min), making them an efficacious diagnostic agent for the detection of bacterial keratitis. In addition, the SiNPs-Van feature distinct antimicrobial activity, with superior activity of 92.5% at a concentration of 0.5 μg/mL against Staphylococcus aureus (S. aureus); comparatively, the antimicrobial rate of free vancomycin is 23.3% at the same concentration. We further explore the SiNPs-Van agents as eye drops for therapy of S. aureus-induced bacterial keratitis on rat model. Represented by slit-lamp scores, the keratitis severity of SiNPs-Van-treated corneas is 3.4, which is 59.6% and 77.3% slighter than vancomycin-(8.2 score) and PBS-treated corneas (15.0 score), respectively. The infected corneas recover to normal (1 score) after 7-d of SiNPs-Van treatment. Above results suggest that the SiNPs-Van could serve as a new kind of high-quality nanotheranostic agents, especially suitable for simultaneous diagnosis and therapy of Gram-positive bacteria keratitis.

Keywords

bacterial keratitisbio-imagingtheranostic probesilicon nanoparticles

Electronic Supplementary Material

Download File(s)
12274_2020_3039_MOESM1_ESM.pdf (1.9 MB)

References

[1]
A. Austin,; T. Lietman,; J. Rose-Nussbaumer, Update on the management of infectious keratitis. Ophthalmology 2017, 124, 1678-1689.
Google Scholar
[2]
S. Lakhundi,; R. Siddiqui,; N. A. Khan, Pathogenesis of microbial keratitis. Microb. Pathog. 2017, 104, 97-109.
Google Scholar
[3]
F. J. Hernandez,; L. Y. Huang,; M. E. Olson,; K. M. Powers,; L. I. Hernandez,; D. K. Meyerholz,; D. R. Thedens,; M. A. Behlke,; A. R. Horswill,; J. O. McNamara, Noninvasive imaging of Staphylococcus aureus infections with a nuclease-activated probe. Nat. Med. 2014, 20, 301-306.
Google Scholar
[4]
P. A. Thomas,; P. Geraldine, Infectious keratitis. Curr. Opin. Infect. Dis. 2007, 20, 129-141.
Google Scholar
[5]
H. J. Jian,; R. S. Wu,; T. Y. Lin,; Y. J. Li,; H. J. Lin,; S. G. Harroun,; J. Y. Lai,; C. C. Huang, Super-cationic carbon quantum dots synthesized from spermidine as an eye drop formulation for topical treatment of bacterial keratitis. ACS Nano 2017, 11, 6703-6716.
Google Scholar
[6]
S. J. Ong,; Y. C. Huang,; H. Y. Tan,; D. H. K. Ma,; H. C. Lin,; L. K. Yeh,; P. Y. F. Chen,; H. C. Chen,; C. C. Chuang,; C. J. Chang, et al. Staphylococcus aureus keratitis: A review of hospital cases. PLoS One 2013, 8, e80119.
Google Scholar
[7]
A. Lin,; M. K. Rhee,; E. K. Akpek,; G. Amescua,; M. Farid,; F. J. Garcia-Ferrer,; D. M. Varu,; D. C. Musch,; S. P. Dunn,; F. S. Mah, Bacterial keratitis preferred practice pattern ®. Ophthalmology 2019, 126, 1-55.
Google Scholar
[8]
W. C. Mak,; K. Y. Cheung,; J. Orban,; C. J. Lee,; A. P. F. Turner,; M. Griffith, Surface-engineered contact lens as an advanced theranostic platform for modulation and detection of viral infection. ACS Appl. Mater. Interfaces 2015, 7, 25487-25494.
Google Scholar
[9]
M. M. Tang,; X. Y. Ji,; H. Xu,; L. Zhang,; A. R. Jiang,; B. Song,; Y. Y. Su,; Y. He, Photostable and biocompatible fluorescent silicon nanoparticles-based theranostic probes for simultaneous imaging and treatment of ocular neovascularization. Anal. Chem. 2018, 90, 8188-8195.
Google Scholar
[10]
Y. F. Wang,; C. H. Liu,; T. J. Ji,; M. Mehta,; W. P. Wang,; E. Marino,; J. Chen,; D. S. Kohane, Intravenous treatment of choroidal neovascularization by photo-targeted nanoparticles. Nat. Commun. 2019, 10, 804.
Google Scholar
[11]
F. Peng,; Y. Y. Su,; Y. L. Zhong,; C. H. Fan,; S. T. Lee,; Y. He, Silicon nanomaterials platform for bioimaging, biosensing, and cancer therapy. Acc. Chem. Res. 2014, 47, 612-623.
Google Scholar
[12]
M. Montalti,; A. Cantelli,; G. Battistelli, Nanodiamonds and silicon quantum dots: Ultrastable and biocompatible luminescent nanoprobes for long-term bioimaging. Chem. Soc. Rev. 2015, 44, 4853-4921.
Google Scholar
[13]
C. X. Song,; Y. L. Zhong,; X. X. Jiang,; F. Peng,; Y. M. Lu,; X. Y. Ji,; Y. Y. Su,; Y. He, Peptide-conjugated fluorescent silicon nanoparticles enabling simultaneous tracking and specific destruction of cancer cells. Anal. Chem. 2015, 87, 6718-6723.
Google Scholar
[14]
Y. Y. Su,; X. Y. Ji,; Y. He, Water-dispersible fluorescent silicon nanoparticles and their optical applications. Adv. Mater. 2016, 28, 10567-10574.
Google Scholar
[15]
B. Song,; Y. He, Fluorescent silicon nanomaterials: From synthesis to functionalization and application. Nano Today 2019, 26, 149-163.
Google Scholar
[16]
F. Erogbogbo,; K. T. Yong,; I. Roy,; R. Hu,; W. C. Law,; W. W. Zhao,; H. Ding,; F. Wu,; R. Kumar,; M. T. Swihart, et al. In vivo targeted cancer imaging, sentinel lymph node mapping and multi-channel imaging with biocompatible silicon nanocrystals. ACS Nano 2011, 5, 413-423.
Google Scholar
[17]
Q. Li,; T. Y. Luo,; M. Zhou,; H. Abroshan,; J. C. Huang,; H. J. Kim,; N. L. Rosi,; Z. Z. Shao,; R. C. Jin, Silicon nanoparticles with surface nitrogen: 90% quantum yield with narrow luminescence bandwidth and the ligand structure based energy law. ACS Nano 2016, 10, 8385-8393.
Google Scholar
[18]
X. Y. Ji,; D. X. Guo,; B. Song,; S. C. Wu,; B. B. Chu,; Y. Y. Su,; Y. He, Traditional Chinese medicine molecule-assisted chemical synthesis of fluorescent anti-cancer silicon nanoparticles. Nano Res. 2018, 11, 5629-5641.
Google Scholar
[19]
X. Y. Ji,; F. Peng,; Y. L. Zhong,; Y. Y. Su,; X. X. Jiang,; C. X. Song,; L. Yang,; B. B. Chu,; S. T. Lee,; Y. He, Highly fluorescent, photostable, and ultrasmall silicon drug nanocarriers for long-term tumor cell tracking and in-vivo cancer therapy. Adv. Mater. 2015, 27, 1029-1034.
Google Scholar
[20]
D. X. Guo,; X. Y. Ji,; F. Peng,; Y. L. Zhong,; B. B. Chu,; Y. Y. Su,; Y. He, Photostable and biocompatible fluorescent silicon nanoparticles for imaging-guided co-delivery of siRNA and doxorubicin to drug-resistant cancer cells. Nano-Micro Lett. 2019, 11, 27.
Google Scholar
[21]
J. L. Tang,; B. B. Chu,; J. H. Wang,; B. Song,; Y. Y. Su,; H. Y. Wang,; Y. He, Multifunctional nanoagents for ultrasensitive imaging and photoactive killing of Gram-negative and Gram-positive bacteria. Nat. Commun. 2019, 10, 4057.
Google Scholar
[22]
P. C. Brooks,; A. M. P. Montgomery,; M. Rosenfeld,; R. A. Reisfeld,; T. H. Hu,; G. Klier,; D. A. Cheresh, Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 1994, 79, 1157-1164.
Google Scholar
[23]
R. O. Hynes, Integrins: Bidirectional, allosteric signaling machines. Cell 2002, 110, 673-687.
Google Scholar
[24]
G. Valente,; N. Depalo,; I. de Paola,; R. M. Iacobazzi,; N. Denora,; V. Laquintana,; R. Comparelli,; E. Altamura,; T. Latronico,; M. Altomare, et al. Integrin-targeting with peptide-bioconjugated semiconductor-magnetic nanocrystalline heterostructures. Nano Res. 2016, 9, 644-662.
Google Scholar
[25]
A. Lagunas,; A. G. Castaño,; J. M. Artés,; Y. Vida,; D. Collado,; E. Pérez-Inestrosa,; P. Gorostiza,; S. Claros,; J. A. Andrades,; J. Samitier, Large-scale dendrimer-based uneven nanopatterns for the study of local arginine-glycine-aspartic acid (RGD) density effects on cell adhesion. Nano Res. 2014, 7, 399-409.
Google Scholar
[26]
B. K. Hubbard,; C. T. Walsh, Vancomycin assembly: Nature's way. Angew. Chem., Int. Ed. 2003, 42, 730-765.
Google Scholar
[27]
J. Xie,; J. G. Pierce,; R. C. James,; A. Okano,; D. L. Boger, A redesigned vancomycin engineered for dual D-Ala-D-Ala and D-Ala-D-Lac binding exhibits potent antimicrobial activity against vancomycin-resistant bacteria. J. Am. Chem. Soc. 2011, 133, 13946-13949.
Google Scholar
[28]
J. H. Ch'ng,; K. K. L. Chong,; L. N. Lam,; J. J. Wong,; K. A. Kline, Biofilm-associated infection by enterococci. Nat. Rev. Microbiol. 2019, 17, 82-94.
Google Scholar
[29]
X. J. Guo,; B. Cao,; C. Y. Wang,; S. Y. Lu,; X. L. Hu, In vivo photothermal inhibition of methicillin-resistant Staphylococcus aureus infection by in situ templated formulation of pathogen-targeting phototheranostics. Nanoscale 2020, 12, 7651-7659.
Google Scholar
[30]
Y. L. Zhong,; X. T. Sun,; S. Y. Wang,; F. Peng,; F. Bao,; Y. Y. Su,; Y. Y. Li,; S. T. Lee,; Y. He, Facile, large-quantity synthesis of stable, tunable-color silicon nanoparticles and their application for long-term cellular imaging. ACS Nano 2015, 9, 5958-5967.
Google Scholar
[31]
W. F. Chen,; Y. Wang,; M. Qin,; X. D. Zhang,; Z. R. Zhang,; X. Sun,; Z. Gu, Bacteria-driven hypoxia targeting for combined biotherapy and photothermal therapy. ACS Nano 2018, 12, 5995-6005.
Google Scholar
[32]
X. L. Liu,; M. G. Li,; T. Han,; B. Cao,; Z. J. Qiu,; Y. Y. Li,; Q. Y. Li,; Y. B. Hu,; Z. Y. Liu,; J. W. Y. Lam, et al. In situ generation of azonia-containing polyelectrolytes for luminescent photopatterning and superbug killing. J. Am. Chem. Soc. 2019, 141, 11259-11268.
Google Scholar
[33]
X. Zhai,; B. Song,; B. B. Chu,; Y. Y. Su,; H. Y. Wang,; Y. He, Highly fluorescent, photostable, and biocompatible silicon theranostic nanoprobes against Staphylococcus aureus infections. Nano Res. 2018, 11, 6417-6427.
Google Scholar
[34]
A. J. Kell,; G. Stewart,; S. Ryan,; R. Peytavi,; M. Boissinot,; A. Huletsky,; M. G. Bergeron,; B. Simard, Vancomycin-modified nanoparticles for efficient targeting and preconcentration of Gram-positive and Gram-negative bacteria. ACS Nano 2008, 2, 1777-1788.
Google Scholar
[35]
S. Gardete,; A. Tomasz, Mechanisms of vancomycin resistance in Staphylococcus aureus. J. Clin. Invest. 2014, 124, 2836-2840.
Google Scholar
[36]
X. D. Zhang,; X. K. Chen,; J. J. Yang,; H. R. Jia,; Y. H. Li,; Z. Chen,; F. G. Wu, Quaternized silicon nanoparticles with polarity-sensitive fluorescence for selectively imaging and killing gram-positive bacteria. Adv. Funct. Mater. 2016, 26, 5958-5970.
Google Scholar
[37]
X. N. Li,; S. M. Robinson,; A. Gupta,; K. Saha,; Z. W. Jiang,; D. F. Moyano,; A. Sahar,; M. A. Riley,; V. M. Rotello, Functional gold nanoparticles as potent antimicrobial agents against multi-drug-resistant bacteria. ACS Nano 2014, 8, 10682-10686.
Google Scholar
[38]
H. W. Gu,; P. L. Ho,; E. Tong,; L. Wang,; B. Xu, Presenting vancomycin on nanoparticles to enhance antimicrobial activities. Nano Lett. 2003, 3, 1261-1263.
Google Scholar
[39]
A. Parmar,; R. Lakshminarayanan,; A. Iyer,; V. Mayandi,; E. T. L. Goh,; D. G. Lloyd,; M. L. S. Chalasani,; N. K. Verma,; S. H. Prior,; R. W. Beuerman, et al. Design and syntheses of highly potent teixobactin analogues against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in vitro and in vivo. J. Med. Chem. 2018, 61, 2009-2017.
Google Scholar
[40]
D. O. Girgis,; G. D. Sloop,; J. M. Reed,; R. J. O'Callaghan, A new topical model of Staphylococcus corneal infection in the mouse. Invest. Ophthalmol. Vis. Sci. 2003, 44, 1591-1597.
Google Scholar
[41]
Y. Qiao,; J. He,; W. Y. Chen,; Y. H. Yu,; W. L. Li,; Z. Du,; T. T. Xie,; Y. Ye,; S. Y. Hua,; D. N. Zhong, et al. Light-activatable synergistic therapy of drug-resistant bacteria-infected cutaneous chronic wounds and nonhealing keratitis by cupriferous hollow nanoshells. ACS Nano 2020, 14, 3299-3315.
Google Scholar
[42]
F. Peng,; M. I. Setyawati,; J. K. Tee,; X. G. Ding,; J. P. Wang,; M. E. Nga,; H. K. Ho,; D. T. Leong, Nanoparticles promote in vivo breast cancer cell intravasation and extravasation by inducing endothelial leakiness. Nat. Nanotechnol. 2019, 14, 279-286.
Google Scholar
[43]
M. I. Setyawati,; C. Y. Tay,; S. L. Chia,; S. L. Goh,; W. Fang,; M. J. Neo,; H. C. Chong,; S. M. Tan,; S. C. J. Loo,; K. W. Ng, et al. Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherin. Nat. Commun. 2013, 4, 1673.
Google Scholar
Nano Research
Volume 14 Issue 1,
January 2021
Pages 52-58
DOI: 10.1007/s12274-020-3039-7
Cite this article:
Zhang L, Ji X, Su Y, et al. Fluorescent silicon nanoparticles-based nanotheranostic agents for rapid diagnosis and treatment of bacteria-induced keratitis. Nano Research, 2021, 14(1): 52-58. https://doi.org/10.1007/s12274-020-3039-7
Topics:
Bacteria DiagnosisFluorescenceNanoparticlesSiliconTheranostics

911

Views

28

Crossref

0

Web of Science

27

Scopus

4

CSCD

Altmetrics
Received: 17 June 2020
Revised: 04 August 2020
Accepted: 04 August 2020
Published: 05 January 2021
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature
Return