More is less: Creation of pathogenic microbe-related theranostic oriented AIEgens.
Rong Hu1, Qiyun Deng1, Qiaoyang Tang1, Rongyuan Zhang2, Lirong Wang1, Bo Situ3, Chen Gui4, Zhiming Wang1, Ben Zhong Tang4, Ben Zhong Tang1 •
TL;DR: In this paper, a multifunctional nanoprobe for selective lighting-up of fungi and targeted anti-microbes was designed and achieved based on the principle of "More is Less", where the hydroxyl groups and alkaline diethylamino moiety facilitate the probe with well aggregation-induced emission feature, good selectivity towards fungi and acid responsiveness.
About: This article is published in Biomaterials.The article was published on 2021-03-02. It has received 18 citations till now. The article focuses on the topics: Nanoprobe.
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Abstract: The emergence of the concept of aggregation-induced emission (AIE) has opened new opportunities in many research areas, such as biopsy analysis, biological processes monitoring, and elucidation of key physiological and pathological behaviors. As a new class of luminescent materials, AIE luminogens (AIEgens) possess many prominent advantages such as tunable molecular structures, high molar absorptivity, high brightness, large Stokes shift, excellent photostability, and good biocompatibility. The past two decades have witnessed a dramatic growth of research interest in AIE, and many AIE-based bioprobes with excellent performance have been widely explored in biomedical fields. This review summarizes some of the latest advancements of AIE molecular probes and AIE nanoparticles (NPs) with regards to biomedical and healthcare applications. According to the research areas, the review is divided into five sections, which are imaging and identification of cells and bacteria, photodynamic therapy, multimodal theranostics, deep tissue imaging, and fluorescence-guided surgery. The challenges and future opportunities of AIE materials in the advanced biomedical fields are briefly discussed. In perspective, the AIE-based bioprobes play vital roles in the exploration of advanced bioapplications for the ultimate goal of addressing more healthcare issues by integrating various cutting-edge modalities and techniques.
23 citations
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TL;DR: In this article , an unprecedented Cd-MOF-based sensor with multiple fluorescence response behaviors towards antibiotics and bacteria was developed, which showed a low limit of detection (LOD, 47 CFU/mL) accompanied with specificity in the detection of S. albus in fetal calf serum and river water.
19 citations
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Christian Büchel1, Quan-Quan Li2, Quan-Quan Li3, Ming-Jie Wen2, Yu-Sen Zhang2, Zi-Sheng Guo2, Xue Bai3, Xue Bai2, Jinxi Song3, Ping Liu2, Yao-Yu Wang2, Jianli Li2 •
TL;DR: In this article, an unprecedented Cd-MOF-based sensor with multiple fluorescence response behaviors towards antibiotics and bacteria was developed, which showed a low limit of detection (LOD, 47 CFU/mL) accompanied with specificity in the detection of S. albus in fetal calf serum and river water.
19 citations
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TL;DR: In this paper, a review of the applications of aggregation-induced emission luminogens (AIEgens) for the treatment of pathogenic bacteria, fungi, and viruses is presented.
Abstract: The prevention and control of pathogenic bacteria, fungi, and viruses is a herculean task for all the countries since they greatly threaten global public health. Rapid detection and effective elimination of these pathogens is crucial for the treatment of related diseases. It is urgently demanded to develop new diagnostic and therapeutic strategies to combat bacteria, fungi, and viruses-induced infections. The emergence of aggregation-induced emission (AIE) luminogens (AIEgens) is a revolutionary breakthrough for the treatment of many diseases, including pathogenic infections. In this review, the main focus is on the applications of AIEgens for theranostic treatment of pathogenic bacteria, fungi, and viruses. Due to the AIE characteristic, AIEgens are promising fluorescent probes for the detection of bacteria, fungi, and viruses with excellent sensitivity and photostability. Moreover, AIEgen-based theranostic platforms can be fabricated by introducing bactericidal moieties or designing AIE photosensitizers and AIE photothermal agents. The current strategies and ongoing developments of AIEgens for the treatment of pathogenic bacteria, fungi, and viruses will be discussed in detail.
17 citations
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TL;DR: β-PM-PIO can achieve superb antibacterial and antibiofilm performance against Gram-positive bacteria with less potential of developing drug resistance, and holds excellent anti-infection capacity against drug-resistant bacteria in vivo with negligible side effects.
Abstract: Developing effective therapies to fight against biofilm-associated infection is extremely urgent. The complex environment of biofilm forces the bacteria to evade the elimination of antibiotics, resulting in recalcitrant chronic infections. To address this issue, a cationic antibacterial agent based on phosphindole oxide (β-PM-PIO) is designed and prepared. The unique molecular structure endows β-PM-PIO with aggregation-induced emission feature and efficient singlet oxygen generation ability. β-PM-PIO shows excellent visual diagnostic function to planktonic bacteria and biofilm. In addition, owing to the synergistic effect of phototoxicity and dark toxicity, β-PM-PIO can achieve superb antibacterial and antibiofilm performance against Gram-positive bacteria with less potential of developing drug resistance. Notably, β-PM-PIO also holds excellent anti-infection capacity against drug-resistant bacteria in vivo with negligible side effects. This work offers a promising platform to develop advanced antibacterial agents against multidrug-resistant bacterial infection.
15 citations
References
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TL;DR: As the need for new antibiotics becomes more pressing, could the design of anti-infective drugs based on the design principles these molecules teach us?
Abstract: Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes. How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?
7,657 citations
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TL;DR: The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery, and future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound.
Abstract: Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound.
1,306 citations
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Jiechao Ge1, Minhuan Lan1, Bingjiang Zhou1, Weimin Liu1, Liang Guo1, Hui Wang1, Qingyan Jia1, Guangle Niu1, Xing Huang1, Hangyue Zhou1, Xiang-Min Meng1, Pengfei Wang1, Chun-Sing Lee2, Wenjun Zhang2, Xiaodong Han3 •
TL;DR: This work presents a new PDT agent based on graphene quantum dots (GQDs) that can produce 1O2 via a multistate sensitization process, resulting in a quantum yield of ~1.3, the highest reported for PDT agents.
Abstract: Clinical applications of current photodynamic therapy (PDT) agents are often limited by their low singlet oxygen ((1)O2) quantum yields, as well as by photobleaching and poor biocompatibility. Here we present a new PDT agent based on graphene quantum dots (GQDs) that can produce (1)O2 via a multistate sensitization process, resulting in a quantum yield of ~1.3, the highest reported for PDT agents. The GQDs also exhibit a broad absorption band spanning the UV region and the entire visible region and a strong deep-red emission. Through in vitro and in vivo studies, we demonstrate that GQDs can be used as PDT agents, simultaneously allowing imaging and providing a highly efficient cancer therapy. The present work may lead to a new generation of carbon-based nanomaterial PDT agents with overall performance superior to conventional agents in terms of (1)O2 quantum yield, water dispersibility, photo- and pH-stability, and biocompatibility.
1,088 citations
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TL;DR: The PTP/TPPN technique provides a promising application in photodynamic inactivation of bacteria on the basis of enhanced energy transfer offered by light-harvesting conjugated polymers.
Abstract: With the increasing antibiotic resistance of microorganisms, there is a growing interest in the design and development of new materials that are effective in killing bacteria to replace conventional antibiotics. Herein, a new anionic water-soluble polythiophene (PTP) and a cationic porphyrin (TPPN) are synthesized and characterized. They can form a complex through electrostatic interactions, and efficient energy transfer from PTP to TPPN occurs upon irradiation under white light (400-800 nm). The energy of TPPN transfers to triplet by intersystem crossing, followed by sensitization of oxygen molecule to enhance the efficiency of singlet oxygen generation related to TPPN itself. The positive charges of PTP/TPPN complex promote its adsorption to the negatively charged bacteria membranes of gram-negative Escherichia coli and gram-positive Bacillus subtilis through electrostatic interactions, and the singlet oxygen effectively kills the bacteria. The photosensitized inactivation of bacteria for the PTP/TPPN complex is efficient, and about 70% reduction of bacterial viability is observed after only 5 min of irradiation with white light at a fluence rate of 90 mW x cm(-2) (27 J x cm(-2)). The technique provides a promising application in photodynamic inactivation of bacteria on the basis of enhanced energy transfer offered by light-harvesting conjugated polymers.
306 citations
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TL;DR: A new kind of supramolecular photosensitizer has been designed, which can be used as bulky “noncovalent building blocks” to weaken the close stacking of porphyrins, thus suppressing the self-quenching of the excited states and improving the antibacterial efficiencies even upon aggregation.
Abstract: Photosensitizers, a key component in photodynamic therapy (PDT), are compounds that can transfer the energy of light to surrounding oxygen, thereby producing highly reactive oxygen species, for example singlet oxygen (O2), to destroy diseased tissues or microorganisms. From a practical application point of view, readily accessible, highly fluorescent photosensitizers with strong absorbance at long wavelengths and high singlet oxygen quantum yields are highly desirable. In particular, porphyrins and their derivatives are popularly employed as one class of important photosensitizers owing to their excellent photophysical properties. They have very intense absorption bands in the visible region and high singlet oxygen quantum yield because of their large p-conjugated aromatic domains. However, the porphyrins easily form aggregates based on hydrophobic p–p interactions in aqueous medium, especially at high local concentrations induced by uptake and accumulation processes inside cells or microorganisms. The aggregation can produce a severe selfquenching effect of the excited state, leading to quenched fluorescence and greatly reducing the ability for O2 generation, and therefore lowering the efficiency for phototherapy. To address this issue, it has been common practice to introduce space-demanding hydrophilic substituents to the parent porphyrins, for example, segregate porphyrins into the focal core of hydrophilic dendrimers. In doing so, the quenching effect can be suppressed, which leads to an appreciable improvement of the photocytotoxicity. However, such covalent practice often involves time-consuming tedious chemical synthesis and purification processes, thus raising the costs of preparation. In addition, organic solvents and toxic reagents used in chemical synthesis may be incorporated into photosensitizers and reduce their biocompatibility. Cucurbit[n]uril (CB[n]), a family of barrel-shaped macrocyclic hosts, have been developed into an interesting research area, because of their rich host–guest chemistry. The CB[n] molecules possess a hydrophilic exterior and hydrophobic cavities. Because of the existence of the hydrophobic cavity, CB[n] has been widely used, for example, to encapsulate and solubilize dyes and to enhance weak supramolecular interactions. Generally, compared with other hosts, such as cyclodextrins and calixarenes, the binding constant of CB[n] with its guests is much larger, especially to the cationic species, driven by a combination of ion–dipole interactions, hydrogen bonds, and the hydrophobic effect. Herein, the large molecular volume and hydrophilic exterior of CB[n] molecules have encouraged us to explore the possibility of using CB[n] as bulky “noncovalent building blocks” to weaken the close stacking of porphyrins, thus suppressing the self-quenching of the excited states and improving the antibacterial efficiencies even upon aggregation. In addition, the rich host–guest chemistry of CB[n] can enable the bulky substituents to be noncovalently attached to the porphyrins, which is environmentally friendly and can greatly decrease the required steps of chemical synthesis. For this purpose, a new kind of supramolecular photosensitizer has been designed as shown in Figure 1. Porphyrins are readily modified with four positive charges (TPOR), so as to efficiently adsorb onto the negative charged surface of bacteria. The other building block, CB[7], is selected as the bulky hydrophilic heads of the supramolecular photosensitizers. The strong host–guest interaction between CB[7] and naphthalene–methylpyridinium moiety on TPOR is used as the driving force for the construction of the supramolecular photosensitizers. For the construction of the desired supramolecular photosensitizers, CB[7] was added to the aqueous solutions of TPOR in a molar ratio of TPOR:CB[7] = 1:4. Different methods were employed to confirm the formation of the desired supramolecular photosensitizers. Firstly, isothermal titration calorimetry (ITC) was carried out to provide information about the binding ability of CB[7] with TPOR. The obtained titration isotherm is shown in Figure 2 a. The binding stoichiometry between TPOR and CB[7] is calculated to be 1:4, indicating that the desired supramolecular photosensitizers shown in Figure 1 have been obtained. By fitting the data, the binding constant of the naphthalene–methylpyridinium subgroup with CB[7] is calculated to be K = 6.6 10m , indicating that the driving force is quite strong and efficient interactions can take place for the noncovalent construction of the TPOR/(CB[7])4 supramolecular photosensitizers. Secondly, the formation of the supramolecular photosensitizers is confirmed by dynamic light scattering [*] K. Liu, Y. L. Liu, Y. X. Yao, Prof. Z. Q. Wang, Prof. X. Zhang Key Lab of Organic Optoelectronics & Molecular Engineering Department of Chemistry, Tsinghua University Beijing 100084 (China) E-mail: xi@mail.tsinghua.edu.cn
270 citations