Photodynamic therapy with a cationic functionalized fullerene rescues mice from fatal wound infections.
Photodynamic therapy with a cationic functionalized fullerene rescues mice from fatal wound infections.
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DOI：
10.2217/nnm.10.98
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发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Hamblin MR
中科院分区：
文献类型：
--
作者：
Lu Z;Dai T;Huang L;Kurup DB;Tegos GP;Jahnke A;Wharton T;Hamblin MR
富勒烯在潜在的生物医学应用方面正在进行深入研究。我们以前曾报道过，C60富勒烯功能化与三个二甲基吡咯烷鎓基团（BF 6）是一种高活性的广谱抗菌光敏剂在体外结合白光照明。我们问这种高度的体外活性是否会转化为体内治疗效果在两个潜在的致命的感染伤口的小鼠模型。我们使用稳定的生物发光细菌和弱光成像系统来非侵入性地真实的跟踪感染的进展。小鼠背部的切除伤口被两种生物发光革兰氏阴性菌种之一污染，奇异变形杆菌（2.5 × 107个细胞）和铜绿假单胞菌（5 × 106个细胞）。将BF 6溶液置于伤口中，随后递送高达180 J/cm 2的宽带白色光（400-700 nm）。在这两种情况下，在对照组（单独的光或单独的BF 6）中未观察到伤口的生物发光的光剂量依赖性减少。富勒烯介导的光动力治疗感染奇异变形杆菌的小鼠的存活率为82%，而未经治疗的存活率为8%（p < 0.001）。对感染高毒力铜绿假单胞菌的小鼠进行光动力疗法不能导致存活，但是当光动力疗法与次优剂量的抗生素妥布霉素（6 mg/kg，持续1天）组合时，存在协同治疗效果，存活率为60%，而单独使用妥布霉素的存活率为20%（p < 0.01）。这些数据表明，阳离子富勒烯具有临床潜力，作为一种抗菌光敏剂，用于浅表感染，其中红光不需要穿透组织。
Fullerenes are under intensive study for potential biomedical applications. We have previously reported that a C60 fullerene functionalized with three dimethylpyrrolidinium groups (BF6) is a highly active broad-spectrum antimicrobial photosensitizer in vitro when combined with white-light illumination. We asked whether this high degree of in vitro activity would translate into an in vivo therapeutic effect in two potentially lethal mouse models of infected wounds. We used stable bioluminescent bacteria and a low light imaging system to follow the progress of the infection noninvasively in real time. An excisional wound on the mouse back was contaminated with one of two bioluminescent Gram-negative species, Proteus mirabilis (2.5 × 107 cells) and Pseudomonas aeruginosa (5 × 106 cells). A solution of BF6 was placed into the wound followed by delivery of up to 180 J/cm2 of broadband white light (400–700 nm). In both cases there was a light-dose-dependent reduction of bioluminescence from the wound not observed in control groups (light alone or BF6 alone). Fullerene-mediated photodynamic therapy of mice infected with P. mirabilis led to 82% survival compared with 8% survival without treatment (p < 0.001). Photodynamic therapy of mice infected with highly virulent P. aeruginosa did not lead to survival, but when photodynamic therapy was combined with a suboptimal dose of the antibiotic tobramycin (6 mg/kg for 1 day) there was a synergistic therapeutic effect with a survival of 60% compared with a survival of 20% with tobramycin alone (p < 0.01). These data suggest that cationic fullerenes have clinical potential as an antimicrobial photosensitizer for superficial infections where red light is not needed to penetrate tissue.
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影响因子：
2.4
作者：
Ragas, Xavier;Dai, Tianhong;Tegos, George P.;Agut, Montserrat;Nonell, Santi;Hamblin, Michael R.
通讯作者：
Hamblin, Michael R.
影响因子：
3.3
作者：
Dai, Tianhong;Huang, Ying-Ying;Hamblin, Michael R.
通讯作者：
Hamblin, Michael R.
影响因子：
6.4
作者：
Hamblin, MR;Zahra, T;Hasan, T
通讯作者：
Hasan, T
影响因子：
4.9
作者：
Isobe, Hiroyuki;Nakanishi, Waka;Nakamura, Eiichi
通讯作者：
Nakamura, Eiichi
影响因子：
3.2
作者：
MARKLEY, K;SMALLMAN, E
通讯作者：
SMALLMAN, E