近红外发光的聚集诱导发光分子在抗菌光动力治疗中的应用

抗生素的误用和滥用,使越来越多的耐药细菌出现,对人类构成致命威胁。近年来,聚集诱导发光材料的发展和生物学科的交叉融合,为治疗细菌感染提供了许多创新思路。相对于紫外/可见光,近红外(NIR)光具有优异的组织深度渗透性和安全性等独特优势,有利于构建光动力抗菌平台进行深度治疗。随着对聚集诱导发光分子(AIEgens)设计及应用的不断探索,AIEgens在光动力抗菌治疗中表现出巨大的应用潜力。本文综述了NIR发光的AIEgens通过光动力疗法治疗细菌感染的研究进展,讨论了不同结构的聚集诱导发光材料存在的主要问题以及该领域当前的挑战和前景。     

聚集诱导发光分子在光动力治疗中的研究进展

光动力治疗(PDT)已成为治疗癌症的重要方法之一。传统光敏剂由于存在选择性差、易光漂白等问题,极大地限制了其在临床上的应用。而具有聚集诱导发光特性的荧光分子(AIEgens),在光照条件下能产生活性氧,并能够将肿瘤细胞杀死,具有治疗癌症的功效。此外,AIEgens还具有易制备、荧光特性优异、生物相容性好以及被动靶向效应(EPR效应)等优点,已被广泛应用于光动力治疗领域,并取得了巨大的发展,具有潜在的医学应用价值。该文主要概括并讨论了近5年来AIEgens在光动力治疗中的研究进展,并进行了展望。     

新型抗菌高分子及其抗菌策略的研究进展

抗菌高分子具有丰富的分子结构和独特的抗菌机制。同时,对微生物具有低耐药性的倾向。这些特点使新型高分子材料在抗菌领域受到人们越来越多的关注。本文首先分析了细菌产生耐药性的原因及由其带来的严峻医学和社会问题;然后系统梳理并探讨了新型抗菌高分子材料（如树状大分子、嵌段共聚物、壳聚糖及其衍生物和抗菌高分子/纳米复合材料等）的结构特点和抗菌机理;最后展望了未来新型功能高分子在抗菌领域的重点延伸及探索方向。     

模拟宿主防御肽的尼龙3抗菌聚合物结构设计、合成及活性研究

微生物感染一直是人类健康的严峻挑战,传统抗生素几乎不可避免地使微生物产生耐药性,因此亟待开发既对耐药细菌、真菌有活性,又不易使微生物产生耐药性的新型抗菌剂.宿主防御肽(host defense peptide,HDP)几乎存在于各种生命形式中并表现出广谱抗菌活性和不易使微生物产生耐药性的特点,近年来作为对抗微生物耐药性的新途径被广泛研究.为解决HDP自身稳定性差(容易被蛋白酶水解)的缺点,多个研究组相继开展HDP模拟物的研究,希望在改善抗菌剂稳定性的同时保持抗菌活性.尼龙3聚合物(β-多肽)是模拟HDP的一类代表性抗菌聚合物.尼龙3聚合物通常由一个亲水性/正电荷亚基和一个疏水性亚基通过不同比例组合来模拟HDP的2个关键性结构特点:正电荷和两亲性结构.通过优化端基基团和聚合物长度、变化亚基的化学结构、探索优化的亲水性/正电荷与疏水性亚基组合以及调节亚基在聚合物中的比例,发现了对多个耐药菌菌株具有高活性和高选择性的尼龙3聚合物.尼龙3对细菌营养细胞和稳定的孢子都显示了活性,同时尼龙3也对游离真菌细胞和真菌生物膜都表现出选择性抗菌活性.这些发现提示了尼龙3对抗微生物耐药性的潜力以及尼龙3作为新型抗菌剂的可能应用.     

光动力抗菌光敏剂的研究进展

光动力抗菌化学疗法是一种结合光敏剂分子和可见光产生的活性氧物种杀灭病原微生物的抗感染治疗方法.活性氧物种能够与致病菌中的多种生物活性分子反应,这一特性使得微生物不易对该方法产生耐药性,这也是该方法近年来备受关注的主要原因.本文重点介绍了近年来光动力抗菌化学疗法领域新型光敏剂药物的研究进展,包括卟啉类衍生物、BODIPY化合物、共轭聚合物和钌多吡啶配合物.     

表面增强拉曼光谱在细菌耐药性评价方面的研究进展

细菌耐药性问题引发全球关注。表面增强拉曼光谱技术(SERS)凭借灵敏度高、检测速度快等优势在评价细菌耐药性应用方面备受关注。本文首先总结了与细菌耐药性评价相关的SERS基底及检测方法,然后对SERS光谱技术在耐药菌和敏感菌鉴定、细菌生物膜成膜性分析与评价及抗菌药物敏感性筛查方面的应用进行总结,最后对SERS技术在细菌检测方面的一些瓶颈问题展开了讨论。希望本文能为SERS技术在细菌耐药性评价方面的应用提供方法指导和思路借鉴。     

新型抗菌高分子及其抗菌机理的研究进展

抗菌高分子具有丰富的分子结构和独特的抗菌机制。同时,对微生物具有低耐药性的倾向。这些特点使新型高分子材料在抗菌领域受到人们越来越多的关注。本文首先分析了细菌产生耐药性的原因及由其带来的严峻医学和社会问题;然后系统梳理并探讨了新型抗菌高分子材料如树状大分子、嵌段共聚物、壳聚糖及其衍生物和抗菌高分子/纳米复合材料等的结构特点和抗菌机理;最后展望了未来新型功能高分子在抗菌领域的重点延伸及探索方向。     

我国研制出“ATP荧光法微生物（细菌总数）快速检测系统”

沈阳中科靓马生物工程有限公司拥有自主知识产权的“ATP荧光法微生物（细菌总数）快速检测系统”项目，已于近日通过了沈阳市科技成果鉴定。除了能够广泛应用于饮料、水处理等行业的细菌总数快速检测外，还可用于血、尿等样品中污染微生物量的检测以及抗菌素抗菌活性、抗癌药物对恶性肿瘤细胞的抑制和杀灭作用的检测。     

无抗生素纳米抗菌剂:现状、挑战与展望

耐药性细菌和生物膜相关的感染性疾病严重威胁全球公众健康。随着纳米技术在抗菌领域的渗透和发展,研发基于无抗生素的新型纳米抗菌剂在避免耐药性产生以及抗菌治疗方式的选择方面提供更多可能性。本文从细菌耐药性的产生机制出发,阐述利用纳米材料自身独特的理化性质,实现自体抗菌;作为纳米酶,利用类酶活性催化底物产生活性氧簇(ROS)等抗菌;随后讨论了构建随内源性/外源性环境刺激响应,以及协同多种新型治疗方式的智能纳米抗菌剂,实现高效抗菌。最后,提出了目前面临的挑战及临床应用前景,为开发更加安全、高效的纳米抗菌剂提供借鉴。     

致病菌与糖的特异性识别及其分析应用研究

致病菌往往通过凝集素-糖特异性识别来实现对宿主细胞的粘附,进而感染宿主组织,引起病变。因此,研究致病菌与糖的特异性识别有利于进一步了解感染性疾病的致病机制,为致病菌的特异性检测和感染性疾病的治疗提供新的策略。该文总结了致病菌-糖特异性识别的相关机制机理;介绍了目前主要的研究方法和技术,特别评述了荧光光谱、表面等离子体共振、电化学阻抗谱及石英晶体微天平等技术在该研究中的应用现状,并对这4种技术与微流控芯片平台的结合进行了探讨;针对致病菌检测特异性差、耐药性严重等难题,重点综述了致病菌-糖的特异性识别在细菌分离、富集、检测、鉴别、生物膜抑制及抗菌糖类药物筛选方面的应用。最后对致病菌-糖特异性识别基础和应用研究进行了展望。     

Aggregation-Induced Emission: Recent Advances in Materials and Biomedical Applications

The concept of aggregation-induced emission (AIE) has opened new opportunities in many research fields. Motivated by the unique feature of AIE fluorogens (AIEgens), during the past decade, many AIE molecular probes and AIE nanoparticle (NP) probes have been developed for sensing, imaging and theranostic applications with excellent performance outperforming conventional fluorescent probes. This Review summarizes the latest advancement of AIE molecular probes and AIE NP probes and their emerging biomedical applications. Special focus is to reveal how the AIE probes are evolved with the development of new multifunctional AIEgens, and how new strategies have been developed to overcome the limitations of traditional AIE probes for more translational applications via fluorescence imaging, photoacoustic imaging and image-guided photodynamic/photothermal therapy. The outlook discusses the challenges and future opportunities for AIEgens to advance the biomedical field.     

Aggregation‐Induced Emission: Recent Advances in Materials and Biomedical Applications

The concept of aggregation‐induced emission (AIE) has opened new opportunities in many research fields. Motivated by the unique feature of AIE fluorogens (AIEgens), during the past decade, many AIE molecular probes and AIE nanoparticle (NP) probes have been developed for sensing, imaging and theranostic applications with excellent performance outperforming conventional fluorescent probes. This Review summarizes the latest advancement of AIE molecular probes and AIE NP probes and their emerging biomedical applications. Special focus is to reveal how the AIE probes are evolved with the development of new multifunctional AIEgens, and how new strategies have been developed to overcome the limitations of traditional AIE probes for more translational applications via fluorescence imaging, photoacoustic imaging and image‐guided photodynamic/photothermal therapy. The outlook discusses the challenges and future opportunities for AIEgens to advance the biomedical field.     

Rational Fabrication and Biomedical Application of Biomolecule‐Conjugated AIEgens through Click Reaction

Recently, the issue of cancer has attracted extensive attention. Early diagnosis and timely therapy are important for cancer treatment. And lots of advanced fluorescent probes have been applied to cancer theranostics. However, the further development of these probes is limited by the disadvantages of poor targeting, weak sensitivity and photobleaching. Fortunately, the emergence of biomolecule‐conjugated fluorescent probes with aggregation‐ induced emission properties has taken innovative impetus to the cancer theranostics. This review summarizes the rational fabrication and biomedical applications of biomolecule‐conjugated AIE luminogens (AIEgens) based on “click reaction” over the past decade. In the meantime, the challenges of biomolecule‐conjugated AIEgens in the field of biomedicine are also discussed.     

Biocompatible and noncytotoxic nucleoside-based AIEgens sensor for lighting-up nucleic acids

Aggregation-induced emission luminogens (AIEgens) have been used in biomacromolecules detection. Herein, TPE-dC and TPE-dU acted as the nucleoside-based AIEgens sensors in the first case, which can be used to detect ctDNA and rRNA in vitro and light up the nucleus in vivo depending on the intermolecular binding affinity. This AIE process enables the quantitative analysis or visualization of nucleic acids in solution or gels state, respectively. Furthermore, confocal laser scanning microscopy (CLSM) images of L929 cells stained with TPE-dC or TPE-dU clearly shows that nucleoside-based AIEgens bio-probes can pass the cell membranes to reach the cell nucleus, without cytotoxicity at the imaging condition (incubation time > 12 h, and 10 μmol/L of concentration). Since the nucleus is rich in DNA/RNA, fluorescence turn-on mode has a great potential in nucleus imaging and clinical diagnosis.     

A Novel Fluorescence Tool for Monitoring Agricultural Industry Chain Based on AIEgens

With the development of the global economy,the safety of agricultural production has attracted intense attention.To minimize the risk of harmful ingredients in the whole industry chain,it is very necessary to cover the entire process of safety inspections from planting to production to environmental management.Fluorescence sensing as a promising and powerful screening tool is widely used for the detection of ions,toxic gases,biological molecules and so on.However,traditional fluorescent probes often suffer from aggregation-induced quenching(ACQ)effects,which limits their practical applications.In this regard,aggregation-induced emission luminogens(AIEgens)can perfectly address this notorious issue and have shown great potential in agricultural safety analysis.In this review,we briefly summarize their applications in agricultural safety monitoring,including the fabrication of agricultural film,agricultural sewage treatment and selective detection of harmful residues in agricultural products.The challenge and future development of AIEgens in this field are also discussed and highlighted.Hopefully,this review can inspire more researchers to participate in this fascinating area.     

Hydrazide–Hydrazone Small Molecules as AIEgens: Illuminating Mitochondria in Cancer Cells

Aggregation-induced-emission luminogens (AIEgens) have gained considerable attention as interesting tools for several biomedical applications, especially for bioimaging due to their brightness and photostability. Numerous AIEgens have been developed for lighting up the subcellular organelles to understand their forms and functions not only healthy but also unhealthy states, such as in cancer cells. However, there is lack of easily synthesizable, biocompatible small molecules for illuminating mitochondria (powerhouses) inside cells. To address this issue, an easy and short synthesis of new biocompatible hydrazide–hydrazone-based small molecules with remarkable aggregation-induced emission (AIE) properties is described. These small-molecule AIEgens showed hitherto unobserved AIE properties due to dual intramolecular H-bonding confirmed by theoretical calculation, pH- and temperature-dependent fluorescence and X-ray crystallographic studies. Confocal microscopy showed that these AIEgens were internalized into the HeLa cervical cancer cells without showing any cytotoxicity. One of the AIEgens was tagged with a triphenylphosphine (TPP) moiety, which successfully localized in the mitochondria of HeLa cells in a selective way compared to L929 noncancerous fibroblast cells. These unique hydrazide–hydrazone-based biocompatible AIEgens can serve as powerful tools to illuminate multiple subcellular organelles to elucidate their forms and functions in cancer cells for next-generation biomedical applications.     

Molecular Design,Circularly Polarized Luminescence,and Helical Self‐Assembly of Chiral Aggregation‐Induced Emission Molecules

Aggregation‐induced emission luminogens (AIEgens) are a new class of luminophors, which are non‐emissive in solution, but emit intensively upon aggregation. By properly designing the chemical structures of the AIEgens, their aggregation process can be tuned towards a desired direction to give diverse novel luminescent architectures of micelles, rods, and helical fibers. AIEgens represent a kind of promising building block for the fabrication of luminescent micro/nanostructures with controllable morphologies. In this review, we describe our recent work in this research area, focusing on the molecular design, circularly polarized luminescence properties, and helical self‐assembly behavior of AIEgens.     

Structural and process controls of AIEgens for NIR-II theranostics

Aggregation-induced emission (AIE) is a cutting-edge fluorescence technology, giving highly-efficient solid-state photoluminescence. Particularly, AIE luminogens (AIEgens) with emission in the range of second near-infrared window (NIR-II, 1000–1700 nm) have displayed salient advantages for biomedical imaging and therapy. However, the molecular design strategy and underlying mechanism for regulating the balance between fluorescence (radiative pathway) and photothermal effect (non-radiative pathway) in these narrow bandgap materials remain obscure. In this review, we outline the latest achievements in the molecular guidelines and photophysical process control for developing highly efficient NIR-II emitters or photothermal agents with aggregation-induced emission (AIE) attributes. We provide insights to optimize fluorescence efficiency by regulating multi-hierarchical structures from single molecules (flexibilization) to molecular aggregates (rigidification). We also discuss the crucial role of intramolecular motions in molecular aggregates for balancing the functions of fluorescence imaging and photothermal therapy. The superiority of the NIR-II region is demonstrated by fluorescence/photoacoustic imaging of blood vessels and the brain as well as photothermal ablation of the tumor. Finally, a summary of the challenges and perspectives of NIR-II AIEgens for in vivo theranostics is given.

Structural and process controls of NIR-II AIEgens realize manipulating of radiative (R) and nonradiative (NR) decay for precise theranostics.     

Strategies for Tumor Hypoxia Imaging Based on Aggregation-Induced Emission Fluorogens

Hypoxia, as a crucial characteristic of cancer, has become an extremely significant direction for researchers to construct fluorescent probes for early diagnosis of tumors. Aggregation-induced emission fluorogens (AIEgens) possess many superior properties to those of conventional fluorophores due to aggregation-induced emission (AIE) features, such as a linear concentration-dependent increase in brightness, remarkable resistance to photobleaching, and the long-term tracking and imaging of cells. Constructing hypoxic response AIEgen-based probes will be very useful for the early diagnosis of tumors. Herein, several hypoxia-responsive probes based on AIEgens reported in the last three years are reported; these examples may lead to the construction of hypoxia-responsive AIE probes used for tumor hypoxia imaging in the future. In addition, typical, conventional hypoxia-responsive bioprobes are presented to further understand hypoxia-responsive fluorescent probes based on AIEgens.