Amphiphilic Star Copolymer-Based Bimodal Fluorogenic/Magnetic Resonance Probes for Concomitant Bacteria Detection and Inhibition
Amphiphilic Star Copolymer-Based Bimodal Fluorogenic/Magnetic Resonance Probes for Concomitant Bacteria Detection and Inhibition
复制标题
基于两亲性星形共聚物的双峰荧光/磁共振探针，用于同时检测和抑制细菌
DOI：
10.1002/adma.201402797
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发表时间：
2014-10-22
影响因子：
29.4
通讯作者：
Liu, Shiyong
中科院分区：
文献类型：
--
作者：
Li, Yamin;Yu, Hansen;Liu, Shiyong
DOI：10.1002/adma. 201402797各种分析物和原位成像/监测病理损伤。[8]例如，Weissleder et al. [4a利用结晶紫、抗体和DNA修饰的磁性纳米颗粒（MNP）对细菌进行MR检测。然而，与基于MNP的T2型MR试剂（其产生负图像对比度）相比，基于产生正对比度的T1型试剂的细菌感测远未被探索。此外，我们设想通过整合两种或更多种检测模式（例如，光学和MR成像）来构建多模式全细菌传感平台将赋予额外的优势，例如补充与每种模式相关的限制、交叉验证和最大化协同效应。[10]至于抗菌剂，已经开发出各种类型的小分子抗生素，并每天用于对抗病原菌。[11]与小分子抗生素相比，大分子抗菌材料具有抗菌效果持久、抗菌谱广等特点，更重要的是，它们易于通过共价或非共价的方式进行功能化。[12]最近，陈等人。[13]报道了一种基于功能化3D纳米线基底的“二合一”细菌检测和消除系统。在此之前，我们制造了聚离子复合物（PIC）胶束纳米粒子，用于同时荧光检测和抑制细菌。[14]然而，细菌传感过程与PIC胶束的解体和发射猝灭性质限制了它们的实际应用，由于妥协的检测灵敏度和操作简便。本文报道了一种基于两亲性星星共聚物的新型细菌检测和抑制平台TPE-星星-P（DMA-co-BMA-co-Gd），由具有充分记录的聚集诱导发射（AIE）特征的四苯乙烯（TPE）核和细菌结合和两亲性/阳离子P（DMA-共-BMA-共-Gd）臂，其中DMA、BMA和Gd分别是甲基丙烯酸2-（二甲氨基）乙酯、甲基丙烯酸丁酯和T1型MR成像造影剂DOTA-Gd。在与带负电荷的细菌表面接触时，静电复合物的形成将限制TPE核的分子内旋转和锚定Gd部分的翻滚移动性，从而导致协同荧光发射开启和MR纵向弛豫速率增强。此外，该星星共聚物还具有针对革兰氏阴性菌（大肠杆菌）的内在抗菌活性。大肠杆菌和铜绿假单胞菌）和革兰氏阳性（S.金黄色葡萄球菌）细菌菌株（方案1）。通过原子转移自由基聚合（ATRP）和后续的后修饰反应，首先合成了结构明确的四臂星形共聚物TPE-star-P（DMA-co-BMA-co-Gd）（方案S1）。[15]炔基封端
DOI: 10.1002/adma. 201402797 various analytes and in situ imaging/monitoring pathological lesions.[8] For example, Weissleder et al.[4a, 9] exploited crystal violet, antibody, and DNA modified magnetic nanoparticles (MNPs) for MR detection of bacteria. In comparison with MNP-based T2-type MR agents which produce a negative image contrast, however, bacterial sensing based on positive contrastgenerating T1-type agents has been far less explored. In addition, we envisage that the construction of multimodal wholebacterium sensing platform by integrating two or more detection modes (eg, optical and MR imaging) would endow extra advantages such as complementing the limitation associated with each modality, cross-validation, and maximizing the synergistic effect.[10]As for antibacterial agents, various types of small molecule antibiotics have been developed and daily used in the battle against pathogenic bacteria.[11] In contrast to small molecule antibiotics, macromolecular antibacterial materials typically exhibit sustained inhibitory effect, broad-spectrum antibacterial feature, and most importantly, they are easy to be functionalized through covalent or non-covalent approaches.[12] Recently, Chen et al.[13] reported a “two-in-one” system for bacteria detection and elimination based on functionalized 3D nanowire substrate. Previously, we fabricated polyion complex (PIC) micellar nanoparticles for simultaneous fluorometric detection and inhibition of bacteria.[14] However, the bacteria sensing process is associated with the disintegration of PIC micelles and the emission quenching nature limits their practical applications due to compromised detection sensitivity and operational ease. Herein we report a new bacteria detection and inhibition platform based on amphiphilic star copolymers, TPE-star-P (DMA-co-BMA-co-Gd), consisting of a tetraphenylethylene (TPE) core with well-documented aggregation-induced emission (AIE) feature, and bacteria-binding and amphiphilic/cationic P (DMA-co-BMA-co-Gd) arms, where DMA, BMA, and Gd are 2-(dimethylamino) ethyl methacrylate, butyl methacrylate, and T1-type MR imaging contrast agent, DOTA-Gd, respectively. Upon contacting with negatively-charged bacterial surfaces, the formation of electrostatic complexes will restrict the intramolecular rotation of TPE cores and tumbling mobility of anchored Gd moieties, thus leading to synergistic fluorescence emission turn-on and MR longitudinal relaxation rate enhancement. Furthermore, the star copolymers possess built-in antibacterial activities against both Gram-negative (E. coli and P. aeruginosa) and Gram-positive (S. aureus) bacteria strains (Scheme 1). By combining atom transfer radical polymerization (ATRP) and successive post-modification reactions, well-defined fourarm star-shaped copolymers, TPE-star-P (DMA-co-BMA-co-Gd), were synthesized at first (Scheme S1).[15] Alkynyl-terminated