Enzyme activated photodynamic therapy for methicillin-resistant Staphylococcus aureus infection both inv itro and in vivo

Fu, Xiaokang; Zhu, Yunqing; Peng, Yung-Hsing; Chen, You-Shuang; Hu, Yi-Ping; Lu, Hua-Xiang; Yu, Wook-Joon; Fang, Yong; Du, Jianzhong; Yao, Min

doi:10.1016/j.jphotobiol.2014.04.016

Cited by 25 publications

(35 citation statements)

References 25 publications

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“…The results demonstrating that the dark-toxicity and the photo-toxicity of 4I against Balb/c 3T3 fibroblasts in vitro showed the 4I-mediated PACT treatment did not produce obvious dark-toxicity in all concentration grades and concentration-dependent differences upon illumination, which were similar to other reports [32, 33]. The cell viability decreased as 4I concentrations increased to or over 3.9 μM, which could be ascribed to the production of ROS.…”

Section: Discussionsupporting

confidence: 88%

Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin conjugate 4I: In vitro and in vivo studies

et al. 2017

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Photodynamic antimicrobial chemotherapy (PACT), as a novel and effective therapeutic modality to eradicate drug resistant bacteria without provoking multidrug resistance, has attracted increasing attention. This study examined the antimicrobial efficacy of the novel cationic amino acid-porphyrin conjugate 4I with four lysine groups against two different clinical isolated strains (drug sensitive and multidrug resistant) of the Acinetobacter baumannii species and its toxicity on murine dermal fibroblasts in vitro, as well as the therapeutic effect of PACT on acute, potentially lethal multidrug resistant strain excisional wound infections in vivo. The PACT protocol exposed 4I to illumination, exhibiting high antimicrobial efficacy on two different strains due to a high yield of reactive oxygen species (ROS) and non-selectivity to microorganisms. The photoinactivation effects of 4I against two different strains were dose-dependent. At 3.9 μM and 7.8 μM, PACT induced 6 log units of inactivation of sensitive and multidrug resistant strains. In contrast, 4I alone and illumination alone treatments had no visibly antimicrobial effect. Moreover, cytotoxicity tests revealed the great safety of the photosensitizer 4I in mice. In the in vivo study, we found 4I-mediated PACT was not only able to kill bacteria but also accelerated wound recovery. Compared with non-treated mice, over 2.89 log reduction of multidrug resistant Acinetobacter baumannii strain was reached in PACT treat mice at 24 h post-treatment. These results imply that 4I-mediated PACT therapy is an effective and safe alternative to conventional antibiotic therapy and has clinical potential for superficial drug-resistant bacterial infections.

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Section: Discussionsupporting

confidence: 88%

Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin conjugate 4I: In vitro and in vivo studies

et al. 2017

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“…The animal species used in the 19 studies were mice (n = 16) and rats (n = 3) . Of the 16 mouse studies, nine used BALB/c mice, 4 utilised Swiss albino mice, two used C57BL/ksj db/db mice, and one used CD1 mice . One study did not report the mouse strain that was used.…”

Section: Resultsmentioning

confidence: 99%

Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies

Sun

Ogawa

Xiao

et al. 2019

International Wound Journal

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Bacterial infection is a common wound complication that can significantly delay healing. Classical local therapies for infected wounds are expensive and are frequently ineffective. One alternative therapy is photodynamic therapy (PDT). We conducted a systematic review to clarify whether PDT is useful for bacteria‐infected wounds in animal models. PubMed and Medline were searched for articles on PDT in infected skin wounds in animals. The language was limited to English. Nineteen articles met the inclusion criteria. The overall study methodological quality was moderate, with a low‐moderate risk of bias. The animal models were mice and rats. The wounds were excisional, burn, and abrasion wounds. Wound size ranged from 6 mm in diameter to 1.5 × 1.5 cm2. Most studies inoculated the wounds with Pseudomonas aeruginosa or methicillin‐resistant Staphylococcus aureus. Eleven and 17 studies showed that the PDT of infected wounds significantly decreased wound size and bacterial counts, respectively. Six, four, and two studies examined the effect of PDT on infected wound‐cytokine levels, wound‐healing time, and body weight, respectively. Most indicated that PDT had beneficial effects on these variables. PDT accelerated bacteria‐infected wound healing in animals by promoting wound closure and killing bacteria.

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“…Theranostic agents could in addition be designed to act as ‘smart drug-delivery vehicles’ that could be activated by a change in the environment of the tumour or the infection such as lower pH [126], redox, enzyme activation [127], elevated temperature or magnetic fields [128]. Furthermore theranostic agents could also be designed to incorporate a method to monitor the effectiveness of treatment, possibly in real-time, and in the days following treatment.…”

Section: Future Directionsmentioning

confidence: 99%

New photosensitizers for photodynamic therapy

Abrahamse

Hamblin

2016

Biochemical Journal

1,593

1,172

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Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound.

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Enzyme activated photodynamic therapy for methicillin-resistant Staphylococcus aureus infection both inv itro and in vivo

Cited by 25 publications

References 25 publications

Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin conjugate 4I: In vitro and in vivo studies

Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin conjugate 4I: In vitro and in vivo studies

Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies

New photosensitizers for photodynamic therapy

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