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Peptide- and Drug-Functionalized Fluorescent Quantum Dots for Enhanced Cell Internalization and Bacterial Debilitation
ACS Applied Bio Materials ( IF 4.7 ) Pub Date : 2020-02-23 , DOI: 10.1021/acsabm.9b01074
Munish Kumar 1 , Satish Pandey 2 , Anuradha Swami 3, 4 , Nishima Wangoo 3 , Saima 1 , Rahul Jain 5 , Rohit K Sharma 1
Affiliation  

This report illustrates a strategy for designing a nanoconjugate derived vector that efficiently delivers antimicrobial drug directly into bacterial cells. The nanoconjugate comprises of negatively charged CDTe@CdS quantum dots (QDs) with its surface functionalized using cationic BP-100 (KKLFKKILKYL-amide), a known cell-penetrating peptide (CPP), via electrostatic approach. The interactions between QD and CPP in QD-functionalized CPPs (QD–CPP) have been well analyzed using fluorescence spectroscopy, gel electrophoresis, and ζ-potential analysis. The QD–CPP conjugate was internalized into Gram negative (Escherichia coli) as well as Gram positive (Staphylococcus aureus) bacterial strains with confocal studies exhibiting a strong signal in tested microorganisms. Further, to check the applicability of QD–CPP conjugate as a delivery vector for generating an effective therapeutics, ampicillin molecules were conjugated on QD–CPP surface to generate QD–CPP–Amp conjugate. The CPP and drug molecules on the surface of QDs were well quantified using high-performance liquid chromatography (HPLC) data. It was observed that the internalization and bacterial debilitation of the QD–CPP–Amp conjugate is 2- to 4-fold effective as compared to that of bare ampicillin. The morphological changes to the bacterial cells upon the treatment with QD–CPP–Amp conjugates were noted with no cytotoxic effect on tested mammalian cell lines. The results inferred that the proposed QD–CPP vector provides a targeted and proficient approach for cellular internalization of cargo (drug) in bacterial cells with effective tracking through florescent QDs.

中文翻译:

用于增强细胞内化和细菌衰弱的肽和药物功能化荧光量子点

本报告说明了一种设计纳米偶联物衍生载体的策略,该载体可有效地将抗菌药物直接输送到细菌细胞中。该纳米共轭物由带负电的 CDTe@CdS 量子点 (QD) 组成,其表面使用阳离子 BP-100 (KKLFKKILKYL-amide)(一种已知的细胞穿透肽 (CPP))通过静电方法进行功能化。QD 功能化 CPP (QD-CPP) 中 QD 和 CPP 之间的相互作用已使用荧光光谱、凝胶电泳和 ζ 电位分析进行了很好的分析。QD-CPP 偶联物被内化到革兰氏阴性(大肠杆菌)和革兰氏阳性(金黄色葡萄球菌)中) 共聚焦研究的细菌菌株在测试的微生物中表现出强烈的信号。此外,为了检查 QD-CPP 偶联物作为产生有效治疗剂的递送载体的适用性,将氨苄青霉素分子偶联在 QD-CPP 表面以生成 QD-CPP-Amp 偶联物。使用高效液相色谱 (HPLC) 数据很好地量化了 QD 表面上的 CPP 和药物分子。据观察,与裸氨苄青霉素相比,QD-CPP-Amp 偶联物的内化和细菌衰弱效果是纯氨苄青霉素的 2 至 4 倍。注意到用 QD-CPP-Amp 缀合物处理后细菌细胞的形态变化,对测试的哺乳动物细胞系没有细胞毒性作用。
更新日期:2020-02-23
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