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Journal ArticleDOI: 10.1016/J.BIOMATERIALS.2021.120725

More is less: Creation of pathogenic microbe-related theranostic oriented AIEgens.

02 Mar 2021-Biomaterials (Elsevier)-Vol. 271, pp 120725-120725
Abstract: Theranostic agents based on photo-dynamic therapy exhibited the properties of the noninvasive feature, spatial-temporal control and be free of drug resistance. Herein, based on the principle of "More is Less", a multifunctional nanoprobe for selective lighting-up of fungi and targeted anti-microbes was designed and achieved. The introducing of the hydroxyl groups and alkaline diethylamino moiety facilitate the probe with well aggregation-induced emission feature, good selectivity towards fungi and acid responsiveness. This probe could only light-up fungi with bright fluorescence, and exhibited diversity anti-microbe behavior towards different microbes. Moreover, the in vitro and in vivo eradication of the supergerm of methicillin resistant staphylococcus aureus was achieved by the treatment of the probe. Confidently, this well-designed nanoprobe is anticipated to have great potential in infective theranostic applications in clinic.

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Topics: Nanoprobe (50%)
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6 results found


Journal ArticleDOI: 10.1002/CMDC.202100138
Lirong Wang1, Rong Hu1, Anjun Qin1, Ben Zhong Tang2  +1 moreInstitutions (2)
05 Aug 2021-ChemMedChem
Abstract: Accurate diagnosis and treatment have been extensively developed in the field of biomedicine, which puts forward higher requirements for the development of biomedical materials with high efficiency and selectivity. Among them, aggregation-induced emission (AIE) conjugated polymers have stood out in recent years owing to their unique properties, such as intense solid emission, high light-harvesting ability, efficient energy transfer, and high 1 O 2 generation ability, which empower them effectively biomedical functions in fluorescence imaging (FL), photodynamic therapy (PDT), FL guided PDT, two-photon excited photodynamic therapy (2PE-PDT), etc . In this review, we highlight recent progress in AIE conjugated polymers and their applications in anticancer and antibacterial areas based on FL and PDT, and summarize the mechanism of color-tuned fluorescent emission and efficient 1 O 2 generation ability compared with small molecular photosensitizer. Last but not least, the challenges and perspectives for the future development of AIE conjugated polymers are discussed.

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2 Citations


Open accessJournal ArticleDOI: 10.3389/FCHEM.2021.715565
Mengmeng Yi1, He Wang1, Miao Wang1, Jianmeng Cao1  +5 moreInstitutions (2)
Abstract: Streptococcus agalactiae, referred to as group B streptococcus (GBS), is a prominent co-pathogenic bacterium causing the onset and death of human, animal, and aquatic products. Although antibiotics are efficient against GBS, antibiotic resistance through antibiotic overuse is an equally serious problem. Therefore, the treatment of GBS infection appears strongly dependent on nonantibiotic therapy, such as photodynamic therapy. Different from other photosensitizers (PSs), luminogens with aggregation-induced emission (AIEgen) can efficiently generate fluorescence and reactive oxygen species (ROS). Herein, TBP-1, an efficient AIE PSs, is chosen to resist GBS, and its antibacterial activity and the killing mechanism toward GBS are investigated. The ROS generation performance and the images of GBS treated with TBP-1 in the dark or under white light irradiation were investigated. TBP-1 with its high ROS generation ability can efficiently kill GBS and serve as a novel treatment strategy against GBS infection.

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Topics: Streptococcus agalactiae (53%)

1 Citations


Journal ArticleDOI: 10.1002/ADHM.202101055
Wei He1, Tianfu Zhang1, Haotian Bai1, Ryan T. K. Kwok1  +2 moreInstitutions (1)
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.

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Journal ArticleDOI: 10.1002/ADHM.202100736
Xiaohui Chen1, Haijie Han1, Zhe Tang1, Qiao Jin1  +1 moreInstitutions (1)
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.

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Journal ArticleDOI: 10.1039/D1BM00894C
Junyong Zhang1, Wencheng Liang1, Lianlei Wen1, Zhimin Lu1  +2 moreInstitutions (1)
Abstract: Combining rapid microbial discrimination with antibacterial properties, multi-functional biomacromolecules allow the timely diagnosis and effective treatment of infectious diseases. Through a two-step approach involving organocatalytic ring-opening copolymerization and thiol-ene modification, aggregation-induced emission (AIE) polycarbonates decorated with tertiary amines were prepared. After being ionized using acetic acid, the obtained cationic AIE polycarbonate with excellent water solubility showed bacteria imaging capabilities and antibacterial activities toward both Gram-positive S. aureus and Gram-negative E. coli. It was indicated via scanning electron microscope images that the bactericidal mechanism involved membrane lysis, consistent with most cationic polymers. Through further co-grafting carboxyl and tertiary amine groups, mixed-charge AIE polycarbonates were obtained. The isoelectric points of such mixed-charge AIE polycarbonates could be simply tuned based on the grafting ratio of positive and negative moieties. Compared with the cationic AIE polycarbonate, mixed-charge AIE polycarbonates allowed the rapid and selective imaging of S. aureus, but not E. coli. The selectivity probably arose from the lower binding forces between the mixed-charge AIE polycarbonates and the low-negative-charge components of the E. coli surface. Therefore, these biodegradable polycarbonates, which integrated selective bacteria imaging and antibiotic abilities, potentially suggest a precision medicine approach for infectious diseases. The overall synthesis approach and mixed-charge AIE polycarbonates provide new references for the design and application of bio-related AIE polymers.

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Topics: Tertiary amine (53%)

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29 results found


Journal ArticleDOI: 10.1038/415389A
Michael Zasloff1Institutions (1)
24 Jan 2002-Nature
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?

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Topics: Antimicrobial peptides (52%)

7,123 Citations


Open accessJournal ArticleDOI: 10.1038/NCOMMS5596
Jiechao Ge1, Minhuan Lan1, Bingjiang Zhou1, Weimin Liu1  +11 moreInstitutions (3)
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.

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Topics: Graphene quantum dot (59%), Singlet oxygen (51%)

887 Citations


Open accessJournal ArticleDOI: 10.1042/BJ20150942
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.

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883 Citations


Journal ArticleDOI: 10.1021/JA904492X
Chengfen Xing1, Qingling Xu1, Hongwei Tang1, Libing Liu1  +1 moreInstitutions (1)
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.

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Topics: Singlet oxygen (53%), Porphyrin (51%)

270 Citations


Journal ArticleDOI: 10.1002/ANIE.201303387
Kai Liu1, Yiliu Liu1, Yuxing Yao1, Huanxiang Yuan2  +3 moreInstitutions (2)
05 Aug 2013-Angewandte Chemie
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

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230 Citations


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