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三种载吲哚菁绿的金属有机框架对抗粪肠球菌的抗菌光动力疗法评估。

Antimicrobial photodynamic therapy assessment of three indocyanine green-loaded metal-organic frameworks against Enterococcus faecalis.

机构信息

College of Chemistry, Shahrood University of Technology, Shahrood, P.O. Box 36155-316, Iran.

The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Photodiagnosis Photodyn Ther. 2018 Sep;23:331-338. doi: 10.1016/j.pdpdt.2018.08.004. Epub 2018 Aug 2.

Abstract

BACKGROUND

Antimicrobial photodynamic therapy (aPDT) has emerged as one of the promising non-invasive adjuvant treatments of endodontic infections. The key part of this technique is application of an optimized nontoxic photosensitizer (PS), like indocyanine green (ICG) which when activated by light can destroy bacterial contaminants. Notwithstanding all featured properties of ICG, this PS mainly suffers from the lack of stability and concentration-dependent aggregation. A variety of nanomaterials (NMs) has been widely exploited to improve the stability and efficiency of ICG. The objective of this study was to evaluate and compare the efficiency of three high capacious metal organic frameworks (MOFs) to produce MOF-ICG as novel PSs improving ICG loading, stability and antimicrobial activity. This is first report on ICG-loaded MOFs for aPDT against endodontic infections.

MATERIALS AND METHODS

Three different nano-MOFs were synthesized (denoted as Fe-101, Al-101 and Fe-88), and employed for ICG loading (MOF-ICG). The stability of immobilized ICG, antimicrobial and anti-biofilm properties of MOF-ICG against Enterococcus faecalis (E. faecalis) as one of the main factors of endodontic infections as well as expression ratio of the esp gene in E. faecalis were evaluated.

RESULTS

Fe-101 and Al-101 showed acceptable ICG loading (ICG loading capacity of 16.93 ± 0.32 and 18.17 ± 0.31, respectively) as well as considerable enhanced aqueous stability (percent of degradation were only 14% and 17%, respectively) in comparison to free ICG (percent of degradation was 95%) after 10 days. ICG-free MOFs could surprisingly suppress the viability of E. faecalis after laser irradiation up to 18.1%, 28.8%, and 38.3% for Al-101, Fe-88 and Fe-101, respectively. ICG loaded MOFs mediated aPDT could significantly reduce the count of E. faecalis to 60.72%, 45.12%, and 62.67%, respectively (p < 0.05). The Fe-88-ICG-PDT, Fe-101-ICG-PDT and Al-101-ICG-PDT considerably dropped the biofilm formation of E. faecalis by 37.54%, 47.01% and 53.68% (p < 0.05). The expression of esp gene was also remarkably declined to 4.4-, 6.0- and 6.2-fold after aPDT in the presence of Fe-88-ICG, Al-101-ICG and Fe-101-ICG, respectively (P < 0.05).

CONCLUSION

Owing to the significant features of the Fe-101 including acceptable ICG loading and stability, as well as reasonable antimicrobial effect after ICG loading in comparison to free ICG, it could be considered as a promising nano-PSs in aPDT to remove E. faecalis.

摘要

背景

抗菌光动力疗法(aPDT)已成为牙髓感染的一种有前途的非侵入性辅助治疗方法之一。该技术的关键部分是应用优化的无毒光敏剂(PS),如吲哚菁绿(ICG),其在光激活后可以破坏细菌污染物。尽管 ICG 具有所有特性,但这种 PS 主要受到缺乏稳定性和浓度依赖性聚集的影响。已经广泛利用各种纳米材料(NMs)来提高 ICG 的稳定性和效率。本研究的目的是评估和比较三种高容量金属有机骨架(MOFs)的效率,以制备作为新型 PS 的 MOF-ICG,从而提高 ICG 的负载量、稳定性和抗菌活性。这是首次报道用于牙髓感染的 aPDT 的载 ICG 的 MOFs。

材料和方法

合成了三种不同的纳米 MOF(分别表示为 Fe-101、Al-101 和 Fe-88),并用于负载 ICG(MOF-ICG)。评估了固定化 ICG 的稳定性、MOF-ICG 对粪肠球菌(E. faecalis)的抗菌和抗生物膜特性,以及粪肠球菌中 esp 基因的表达比。

结果

与游离 ICG 相比(降解率为 95%),Fe-101 和 Al-101 表现出可接受的 ICG 负载能力(ICG 负载能力分别为 16.93±0.32%和 18.17±0.31%),以及相当大的增强的水稳定性(降解率仅为 14%和 17%)。令人惊讶的是,无 ICG 的 MOFs 在激光照射后,对粪肠球菌的活力抑制率分别高达 18.1%、28.8%和 38.3%,分别为 Al-101、Fe-88 和 Fe-101。载 ICG 的 MOFs 介导的 aPDT 可显著将粪肠球菌的数量减少至 60.72%、45.12%和 62.67%(p<0.05)。Fe-88-ICG-PDT、Fe-101-ICG-PDT 和 Al-101-ICG-PDT 可使粪肠球菌的生物膜形成分别降低 37.54%、47.01%和 53.68%(p<0.05)。在存在 Fe-88-ICG、Al-101-ICG 和 Fe-101-ICG 的情况下,esp 基因的表达也分别显著下降至 4.4、6.0 和 6.2 倍(P<0.05)。

结论

由于 Fe-101 的显著特征,包括可接受的 ICG 负载和稳定性,以及与游离 ICG 相比,载 ICG 后的合理抗菌效果,它可用作 aPDT 中去除粪肠球菌的有前途的纳米 PS。

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