A nanovehicle developed for treating deep-seated bacteria using low-dose X-ray

Chien Lin Pan, Ming Hong Chen, Fu I. Tung, Tse Ying Liu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Many non-antibiotic strategies, such as photocatalysis and photodynamic therapy, have been proposed to inhibit and/or kill bacteria. However, these approaches still have drawbacks such as insufficient bacterial specificity and the limited penetration depth of ultraviolet and near-infrared light. To overcome these limitations, we developed a bacteria-specific anti-bacterial technique via using low-dose X-ray. Graphene oxide quantum dots (GQDs, a multifunctional vehicle) conjugated with vancomycin (Van, a bacteria-targeting ligand) were assembled with Protoporphyrin IX (PpIX, a photo/radiation sensitizer) to yield a novel Van-GQDs/PpIX complex that specifically attached to Escherichia coli and efficiently generated intracellular reactive oxygen species following X-ray activation. Delivery using GQDs increased the PpIX/Van ratio in the target bacterial cell, damaged bacterial cell wall, and enhanced X-ray-induced PpIX activation. Hence, this approach allowed for the use of a low-dose X-ray to efficiently activate the Van-GQDs/PpIX complex to exert its bactericidal effects on Escherichia coli without damaging normal cells. Furthermore, the E. coli did not develop resistance to the proposed approach for at least 7 rounds of repeated administration during one week. Thus, this proposed vehicle exhibiting bacteria-specific X-ray-triggered toxicity is a promising alternative to antibiotics for treating serious bacterial infections occurring in deep-seated tissues/organs (e.g., osteomyelitis and peritonitis). Statements of Significance Administration of antibiotics is the most common treatment modality for bacterial infections. However, in some cases, patient attributes such as age, health, tolerance to antibiotics do not allow for the use of high-dose antibiotics. In addition, some bacteria develop resistance to antibiotics because of improper and long-term use of these agents. Therefore, non-antibiotic strategies to treat deeply situated bacterial infections, such as osteomyelitis, are urgently needed for avoiding amputation. To date, several non-antibiotic approaches, such as Ag nanoparticles, graphene-based materials, photocatalysis, and photodynamic therapy have been proposed to inhibit and/or kill bacteria. However, the major challenges of photochemical strategies, specificity and limited penetration depth of light source, still remain for treating the deep-seated bacteria. To overcome these problems, we developed a novel nanovehicle that exerted toxic effects specifically on bacteria following activation by a deeply penetrative low-dose X-ray, without damaging normal cells. As such, it realizes a deeply photochemical route for treating the deep-seated bacteria.

Original languageEnglish
Pages (from-to)159-169
Number of pages11
JournalActa Biomaterialia
Volume47
DOIs
Publication statusPublished - Jan 1 2017
Externally publishedYes

Fingerprint

Dosimetry
Bacteria
X-Rays
X rays
Antibiotics
Anti-Bacterial Agents
Bacterial Infections
Escherichia coli
Photodynamic therapy
Graphite
Photocatalysis
Chemical activation
Photochemotherapy
Osteomyelitis
Graphene
Radiation-Sensitizing Agents
Light
Quantum Dots
Poisons
Vancomycin

Keywords

  • Anti-bacterial
  • Graphene oxide quantum dots
  • Protoporphyrin IX
  • Vancomycin
  • X-ray

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

A nanovehicle developed for treating deep-seated bacteria using low-dose X-ray. / Pan, Chien Lin; Chen, Ming Hong; Tung, Fu I.; Liu, Tse Ying.

In: Acta Biomaterialia, Vol. 47, 01.01.2017, p. 159-169.

Research output: Contribution to journalArticle

Pan, Chien Lin ; Chen, Ming Hong ; Tung, Fu I. ; Liu, Tse Ying. / A nanovehicle developed for treating deep-seated bacteria using low-dose X-ray. In: Acta Biomaterialia. 2017 ; Vol. 47. pp. 159-169.
@article{84366d0b09474d12bf808f3dfdf2f727,
title = "A nanovehicle developed for treating deep-seated bacteria using low-dose X-ray",
abstract = "Many non-antibiotic strategies, such as photocatalysis and photodynamic therapy, have been proposed to inhibit and/or kill bacteria. However, these approaches still have drawbacks such as insufficient bacterial specificity and the limited penetration depth of ultraviolet and near-infrared light. To overcome these limitations, we developed a bacteria-specific anti-bacterial technique via using low-dose X-ray. Graphene oxide quantum dots (GQDs, a multifunctional vehicle) conjugated with vancomycin (Van, a bacteria-targeting ligand) were assembled with Protoporphyrin IX (PpIX, a photo/radiation sensitizer) to yield a novel Van-GQDs/PpIX complex that specifically attached to Escherichia coli and efficiently generated intracellular reactive oxygen species following X-ray activation. Delivery using GQDs increased the PpIX/Van ratio in the target bacterial cell, damaged bacterial cell wall, and enhanced X-ray-induced PpIX activation. Hence, this approach allowed for the use of a low-dose X-ray to efficiently activate the Van-GQDs/PpIX complex to exert its bactericidal effects on Escherichia coli without damaging normal cells. Furthermore, the E. coli did not develop resistance to the proposed approach for at least 7 rounds of repeated administration during one week. Thus, this proposed vehicle exhibiting bacteria-specific X-ray-triggered toxicity is a promising alternative to antibiotics for treating serious bacterial infections occurring in deep-seated tissues/organs (e.g., osteomyelitis and peritonitis). Statements of Significance Administration of antibiotics is the most common treatment modality for bacterial infections. However, in some cases, patient attributes such as age, health, tolerance to antibiotics do not allow for the use of high-dose antibiotics. In addition, some bacteria develop resistance to antibiotics because of improper and long-term use of these agents. Therefore, non-antibiotic strategies to treat deeply situated bacterial infections, such as osteomyelitis, are urgently needed for avoiding amputation. To date, several non-antibiotic approaches, such as Ag nanoparticles, graphene-based materials, photocatalysis, and photodynamic therapy have been proposed to inhibit and/or kill bacteria. However, the major challenges of photochemical strategies, specificity and limited penetration depth of light source, still remain for treating the deep-seated bacteria. To overcome these problems, we developed a novel nanovehicle that exerted toxic effects specifically on bacteria following activation by a deeply penetrative low-dose X-ray, without damaging normal cells. As such, it realizes a deeply photochemical route for treating the deep-seated bacteria.",
keywords = "Anti-bacterial, Graphene oxide quantum dots, Protoporphyrin IX, Vancomycin, X-ray",
author = "Pan, {Chien Lin} and Chen, {Ming Hong} and Tung, {Fu I.} and Liu, {Tse Ying}",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.actbio.2016.10.003",
language = "English",
volume = "47",
pages = "159--169",
journal = "Acta Biomaterialia",
issn = "1742-7061",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - A nanovehicle developed for treating deep-seated bacteria using low-dose X-ray

AU - Pan, Chien Lin

AU - Chen, Ming Hong

AU - Tung, Fu I.

AU - Liu, Tse Ying

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Many non-antibiotic strategies, such as photocatalysis and photodynamic therapy, have been proposed to inhibit and/or kill bacteria. However, these approaches still have drawbacks such as insufficient bacterial specificity and the limited penetration depth of ultraviolet and near-infrared light. To overcome these limitations, we developed a bacteria-specific anti-bacterial technique via using low-dose X-ray. Graphene oxide quantum dots (GQDs, a multifunctional vehicle) conjugated with vancomycin (Van, a bacteria-targeting ligand) were assembled with Protoporphyrin IX (PpIX, a photo/radiation sensitizer) to yield a novel Van-GQDs/PpIX complex that specifically attached to Escherichia coli and efficiently generated intracellular reactive oxygen species following X-ray activation. Delivery using GQDs increased the PpIX/Van ratio in the target bacterial cell, damaged bacterial cell wall, and enhanced X-ray-induced PpIX activation. Hence, this approach allowed for the use of a low-dose X-ray to efficiently activate the Van-GQDs/PpIX complex to exert its bactericidal effects on Escherichia coli without damaging normal cells. Furthermore, the E. coli did not develop resistance to the proposed approach for at least 7 rounds of repeated administration during one week. Thus, this proposed vehicle exhibiting bacteria-specific X-ray-triggered toxicity is a promising alternative to antibiotics for treating serious bacterial infections occurring in deep-seated tissues/organs (e.g., osteomyelitis and peritonitis). Statements of Significance Administration of antibiotics is the most common treatment modality for bacterial infections. However, in some cases, patient attributes such as age, health, tolerance to antibiotics do not allow for the use of high-dose antibiotics. In addition, some bacteria develop resistance to antibiotics because of improper and long-term use of these agents. Therefore, non-antibiotic strategies to treat deeply situated bacterial infections, such as osteomyelitis, are urgently needed for avoiding amputation. To date, several non-antibiotic approaches, such as Ag nanoparticles, graphene-based materials, photocatalysis, and photodynamic therapy have been proposed to inhibit and/or kill bacteria. However, the major challenges of photochemical strategies, specificity and limited penetration depth of light source, still remain for treating the deep-seated bacteria. To overcome these problems, we developed a novel nanovehicle that exerted toxic effects specifically on bacteria following activation by a deeply penetrative low-dose X-ray, without damaging normal cells. As such, it realizes a deeply photochemical route for treating the deep-seated bacteria.

AB - Many non-antibiotic strategies, such as photocatalysis and photodynamic therapy, have been proposed to inhibit and/or kill bacteria. However, these approaches still have drawbacks such as insufficient bacterial specificity and the limited penetration depth of ultraviolet and near-infrared light. To overcome these limitations, we developed a bacteria-specific anti-bacterial technique via using low-dose X-ray. Graphene oxide quantum dots (GQDs, a multifunctional vehicle) conjugated with vancomycin (Van, a bacteria-targeting ligand) were assembled with Protoporphyrin IX (PpIX, a photo/radiation sensitizer) to yield a novel Van-GQDs/PpIX complex that specifically attached to Escherichia coli and efficiently generated intracellular reactive oxygen species following X-ray activation. Delivery using GQDs increased the PpIX/Van ratio in the target bacterial cell, damaged bacterial cell wall, and enhanced X-ray-induced PpIX activation. Hence, this approach allowed for the use of a low-dose X-ray to efficiently activate the Van-GQDs/PpIX complex to exert its bactericidal effects on Escherichia coli without damaging normal cells. Furthermore, the E. coli did not develop resistance to the proposed approach for at least 7 rounds of repeated administration during one week. Thus, this proposed vehicle exhibiting bacteria-specific X-ray-triggered toxicity is a promising alternative to antibiotics for treating serious bacterial infections occurring in deep-seated tissues/organs (e.g., osteomyelitis and peritonitis). Statements of Significance Administration of antibiotics is the most common treatment modality for bacterial infections. However, in some cases, patient attributes such as age, health, tolerance to antibiotics do not allow for the use of high-dose antibiotics. In addition, some bacteria develop resistance to antibiotics because of improper and long-term use of these agents. Therefore, non-antibiotic strategies to treat deeply situated bacterial infections, such as osteomyelitis, are urgently needed for avoiding amputation. To date, several non-antibiotic approaches, such as Ag nanoparticles, graphene-based materials, photocatalysis, and photodynamic therapy have been proposed to inhibit and/or kill bacteria. However, the major challenges of photochemical strategies, specificity and limited penetration depth of light source, still remain for treating the deep-seated bacteria. To overcome these problems, we developed a novel nanovehicle that exerted toxic effects specifically on bacteria following activation by a deeply penetrative low-dose X-ray, without damaging normal cells. As such, it realizes a deeply photochemical route for treating the deep-seated bacteria.

KW - Anti-bacterial

KW - Graphene oxide quantum dots

KW - Protoporphyrin IX

KW - Vancomycin

KW - X-ray

UR - http://www.scopus.com/inward/record.url?scp=84991821831&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991821831&partnerID=8YFLogxK

U2 - 10.1016/j.actbio.2016.10.003

DO - 10.1016/j.actbio.2016.10.003

M3 - Article

C2 - 27713087

AN - SCOPUS:84991821831

VL - 47

SP - 159

EP - 169

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1742-7061

ER -