Peptide-modified nanoparticles inhibit formation of Porphyromonas gingivalis biofilms with Streptococcus gordonii.
Peptide-modified nanoparticles inhibit formation of Porphyromonas gingivalis biofilms with Streptococcus gordonii.
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DOI：
10.2147/ijn.s139178
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发表时间：
2017
影响因子：
8
通讯作者：
Steinbach-Rankins JM
中科院分区：
文献类型：
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作者：
Kalia P;Jain A;Radha Krishnan R;Demuth DR;Steinbach-Rankins JM
牙龈卟啉单胞菌与共生链球菌的相互作用促进牙龈卟啉单胞菌在口腔的定植。我们之前的研究表明，从戈登链球菌中提取的合成肽（BAR）可以有效地抑制牙龈卟啉单胞菌/S的形成。在牙周炎小鼠模型中，godonii生物膜（IC50 =1.3µM）可降低牙龈卟啉卟啉菌的毒力。因此，BAR通过限制牙龈假单胞菌在口腔的定植，代表了一种控制牙周炎的新疗法。在这里，我们试图开发含有bar修饰的聚（乳酸-羟基乙酸）酸（PLGA）纳米颗粒（NPs）的潜在口腔药物递送载体。PLGA-NPs最初用棕榈酰化亲和素修饰，随后与生物素化的BAR偶联。用荧光标记肽定量测定BAR修饰的程度。采用两种生物膜模型，比较了bar修饰的NPs与游离肽对牙龈卟啉卟啉粘附的抑制作用。bar修饰的NPs平均尺寸为99±29 nm，表面正电荷比未修饰的NPs多（zeta电位分别为- 7 mV和- 25 mV）。当使用37 nmol BAR/mg亲和素NPs时发生结合饱和，其有效载荷为7.42 nmol BAR/mg NPs。bar修饰的NPs以剂量依赖的方式与牙龈卟啉单胞菌结合，并且更有效地抑制牙龈卟啉单胞菌/S。相对于等量的游离肽（IC50分别为0.2µM和1.3µM）， gordonii粘附和生物膜形成。bar修饰的NPs也破坏了预形成的牙龈假单胞菌/S。Gordonii生物膜比游离肽更有效。最后，我们证明了bar修饰的NPs促进了与牙龈卟啉卟啉的多价关联，这为NPs的有效性增加提供了解释。这些结果表明，与游离肽制剂相比，bar修饰的NPs可提供更高的局部肽剂量，可能是限制牙龈假单胞菌在口腔定植的更有效的治疗方法。
The interaction of Porphyromonas gingivalis with commensal streptococci promotes P. gingivalis colonization of the oral cavity. We previously showed that a synthetic peptide (BAR) derived from Streptococcus gordonii potently inhibited the formation of P. gingivalis/S. gordonii biofilms (IC50 =1.3 µM) and reduced P. gingivalis virulence in a mouse model of periodontitis. Thus, BAR represents a novel therapeutic to control periodontitis by limiting P. gingivalis colonization of the oral cavity. Here, we sought to develop drug-delivery vehicles for potential use in the oral cavity that comprise BAR-modified poly(lactic-co-glycolic)acid (PLGA) nanoparticles (NPs). PLGA-NPs were initially modified with palmitylated avidin and subsequently conjugated with biotinylated BAR. The extent of BAR modification was quantified using a fluorescent-labeled peptide. Inhibition of P. gingivalis adherence to S. gordonii by BAR-modified NPs was compared with free peptide using a two-species biofilm model. BAR-modified NPs exhibited an average size of 99±29 nm and a more positive surface charge than unmodified NPs (zeta potentials of −7 mV and −25 mV, respectively). Binding saturation occurred when 37 nmol BAR/mg of avidin-NPs was used, which resulted in a payload of 7.42 nmol BAR/mg NPs. BAR-modified NPs bound to P. gingivalis in a dose-dependent manner and more potently inhibited P. gingivalis/S. gordonii adherence and biofilm formation relative to an equimolar amount of free peptide (IC50 of 0.2 µM versus 1.3 µM). BAR-modified NPs also disrupted the preformed P. gingivalis/S. gordonii biofilms more effectively than free peptide. Finally, we demonstrate that BAR-modified NPs promoted multivalent association with P. gingivalis, providing an explanation for the increased effectiveness of NPs. These results indicate that BAR-modified NPs deliver a higher local dose of peptide and may represent a more effective therapeutic approach to limit P. gingivalis colonization of the oral cavity compared to treatment with formulations of free peptide.