Topical delivery of low-cost protein drug candidates made in chloroplasts for biofilm disruption and uptake by oral epithelial cells.
Topical delivery of low-cost protein drug candidates made in chloroplasts for biofilm disruption and uptake by oral epithelial cells.
复制标题
DOI：
10.1016/j.biomaterials.2016.07.042
复制
发表时间：
2016-10
期刊：
影响因子：
14
通讯作者：
Koo H
中科院分区：
文献类型：
--
作者：
Liu Y;Kamesh AC;Xiao Y;Sun V;Hayes M;Daniell H;Koo H
蛋白质药物（PD）由于成本高和侵入性手术输送而很少用于牙科医学。破坏有毒口腔生物膜的临床进展有限，尽管它们在引起龋齿方面的患病率很高。抗微生物剂在局部治疗后或渗透和破坏形成的生物膜的效果差是一个主要挑战。我们报告了一个令人兴奋的低成本的方法，使用植物制造的抗菌肽（PMAMPs），retrocyclin或protegrin与复杂的二级结构（环状/发夹）局部使用，以控制生物膜。PMAMPs迅速杀死病原体变形链球菌和受损的生物膜形成后，一个单一的局部应用牙齿模拟表面。此外，我们开发了一种协同方法，使用PMAMPs结合基质降解酶，以促进其进入生物膜和杀死嵌入的细菌。此外，我们确定了PMAMPs在将药物递送到牙周和牙龈细胞中的新作用，比任何其他测试的细胞穿透肽有效13-48倍。因此，与植物细胞中表达的保护蛋白融合的PD可能在将治疗性蛋白质递送至牙龈组织中同时在作为局部口服制剂或在口香糖中递送时杀死病原菌方面潜在地发挥双重作用。最近FDA批准植物生产的PD预示着这一新概念的临床进展。
Protein drugs (PD) are minimally utilized in dental medicine due to high cost and invasive surgical delivery. There is limited clinical advancement in disrupting virulent oral biofilms, despite their high prevalence in causing dental caries. Poor efficacy of antimicrobials following topical treatments or to penetrate and disrupt formed biofilms is a major challenge. We report an exciting low-cost approach using plant-made antimicrobial peptides (PMAMPs) retrocyclin or protegrin with complex secondary structures (cyclic/hairpin) for topical use to control biofilms. The PMAMPs rapidly killed the pathogen Streptococcus mutans and impaired biofilm formation following a single topical application of tooth-mimetic surface. Furthermore, we developed a synergistic approach using PMAMPs combined with matrix-degrading enzymes to facilitate their access into biofilms and kill the embedded bacteria. In addition, we identified a novel role for PMAMPs in delivering drugs to periodontal and gingival cells, 13–48 folds more efficiently than any other tested cell penetrating peptides. Therefore, PDs fused with protegrin expressed in plant cells could potentially play a dual role in delivering therapeutic proteins to gum tissues while killing pathogenic bacteria when delivered as topical oral formulations or in chewing gums. Recent FDA approval of plant-produced PDs augurs well for clinical advancement of this novel concept.