Near-infrared-triggered antibacterial and antifungal photodynamic therapy based on lanthanide-doped upconversion nanoparticles.
Near-infrared-triggered antibacterial and antifungal photodynamic therapy based on lanthanide-doped upconversion nanoparticles.
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DOI：
10.1039/c8nr01967c
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发表时间：
2018-08
期刊：
影响因子：
6.7
通讯作者：
Yuxiang Zhang;Ping Huang;Dong Wang;Jincan Chen;Wenzhen Liu;Ping Hu;Mingdong Huang;Xueyuan Chen-Xueyuan
中科院分区：
文献类型：
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作者：
Yuxiang Zhang;Ping Huang;Dong Wang;Jincan Chen;Wenzhen Liu;Ping Hu;Mingdong Huang;Xueyuan Chen-Xueyuan
全球范围内微生物对传统药物和经典药效基团的耐药性急剧上升，这促使人们寻找新的抗菌化合物。抗菌光动力疗法（aPDT）最近已成为一种有效选择性杀灭细菌和其他致病微生物的方法。然而，一些因素限制了其在临床中的推广应用，这些因素包括疏水性光敏剂（PS）在水性介质中的聚集以及PS的生物分布效率低下。此外，可见光照射下的光激活作用限制了aPDT对深部组织感染的治疗效果。
为克服这些限制，研究人员制备了一种由镧系元素掺杂的上转换纳米颗粒（UCNPs，LiYF4:Yb/Er）和聚乙烯吡咯烷酮（PVP）组成的PS（β-羧基酞菁锌，CPZ）递送系统，并对其抗菌（抗细菌和抗真菌）活性进行了研究。这种近红外（NIR）触发的UCNPs-CPZ-PVP系统显著减少了CPZ的聚集，并且在aPDT后（50 μg mL-1的UCNPs-CPZ-PVP，0.5 W cm-2的980 nm光照），对多重耐药（MDR）细菌（耐甲氧西林金黄色葡萄球菌减少4.7 log10，MDR大肠杆菌减少2.1 log10）表现出较高的抗感染活性。特别是，UCNPs-CPZ-PVP对白色念珠菌显示出高效的抗真菌效果。
研究人员进一步利用MDR细菌感染的小鼠模型，在存在5毫米厚组织标本的情况下进行了体内aPDT实验，证明了UCNPs-CPZ-PVP在治疗深部组织感染方面的巨大潜力。总之，我们揭示了一种高效的近红外触发纳米光敏剂，其在临床抗菌治疗中具有良好的抗真菌和抗菌效果。
An alarming worldwide increase in microbial resistance to traditional drugs and classical pharmacophores has spurred the search for new antimicrobial compounds. Antimicrobial photodynamic therapy (aPDT) has recently emerged as an effective modality for the selective destruction of bacteria and other pathogenic microorganisms. However, some of the factors, including the aggregation of the hydrophobic photosensitizer (PS) in aqueous media and the inefficient biodistribution of PS limit its expansion to clinical conditions. In addition, the photoactivation under visible-light irradiation limits the therapeutic effect of aPDT for deep-tissue infection. To overcome these limitations, a PS (β-carboxyphthalocyanine zinc, CPZ) delivery system with lanthanide-doped upconversion nanoparticles (UCNPs, LiYF4:Yb/Er) and polyvinylpyrrolidone (PVP) was prepared and its antimicrobial (antibacterial and antifungal) activities were investigated. Such a near-infrared (NIR) triggered UCNPs-CPZ-PVP system significantly reduced the aggregation of CPZ and presented a high anti-infectious activity against multi-drug resistant (MDR) bacteria (methicillin-resistant Staphylococcus aureus by 4.7 log10 and MDR Escherichia coli by 2.1 log10) post aPDT (at 50 μg mL-1 UCNPs-CPZ-PVP with 0.5 W cm-2 980 nm light). In particular, UCNPs-CPZ-PVP showed high antifungal efficacy against Candida albicans. In vivo aPDT experiments were further carried out using an MDR bacterial infection murine model in the presence of 5 mm thick tissue specimens, demonstrating the great potential of UCNPs-CPZ-PVP against infections in deep tissue. Altogether, we reveal an efficient NIR-triggered nano-photosensitizer with promising antifungal and antibacterial efficacy for clinical antimicrobial therapy.