Novel photocatalytic carbon dots: efficiently inhibiting amyloid aggregation and quickly disaggregating amyloid aggregates.

Amyloid aggregation is implicated in the pathogenesis of various neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). It is critical to develop high-performance drugs to combat amyloid-related diseases. Most identified nanomaterials exhibit limited biocompatibility and therapeutic efficacy. In this work, we used a solvent-free carbonization process to prepare new photo-responsive carbon nanodots (CNDs). The surface of the CNDs is densely packed with chemical groups. CNDs with large, conjugated domains can interact with proteins through π-π stacking and hydrophobic interactions. Furthermore, CNDs possess the ability to generate singlet oxygen species (1O2) and can be used to oxidize amyloid. The hydrophobic interaction and photo-oxidation can both influence amyloid aggregation and disaggregation. Thioflavin T (ThT) fluorescence analysis and circular dichroism (CD) spectroscopy indicate that CNDs can block the transition of amyloid from an α-helix structure to a ß-sheet structure. CNDs demonstrate efficacy in alleviating cytotoxicity induced by Aß42 and exhibit promising blood-brain barrier (BBB) permeability. CNDs have small size, low biotoxicity, good fluorescence and photocatalytic properties, and provide new ideas for the diagnosis and treatment of amyloid-related diseases.

Research of correlation between personality traits and hormones with the nature of pulmonary nodules.

Background: Rising rates of lung cancer screening have contributed to an increase in pulmonary nodule diagnosis rates. Studies have shown that psychosocial factors and hormones have an impact on the development of the oncological diseases. Therefore, we conducted this study to explore the potential relationship between pulmonary nodules pathology and patient personality traits and hormone levels. Methods: This study enrolled 245 individuals who had first been diagnosed with pulmonary nodules in Tangdu Hospital and admitted for surgery. The personality profile of these patients was analyzed on admission using the C-Type Behavioral Scale and hormone levels were measured in preoperative serum samples. Associations between nodule pathology, personality scores, and hormone levels， were then assessed through Statistical methods analysis. Results: Behavioral scale analyses revealed significant differences four items, including depression, anger outward, optimism, and social support (P< 0.05). Specifically, patients with higher depression scores were more likely to harbor malignant pulmonary nodules, as were patients with lower levels of anger outward, social support, and optimism. Univariate analyses indicated that nodule pathology was associated with significant differences in nodule imaging density, CT value, testosterone levels, and T4 levels(P< 0.05), and logistic regression analyses revealed pulmonary nodule imaging density and T4 levels to be significant differences of nodule pathology. Conclusion: The results showed a significant association between nodules pathology and the personality characteristics of the patients (depression, anger outward, optimism, social support), the patients' T4 levels and the imaging density of the nodules.

Multifunctional Carbon-Dot-Photosensitizer Nanoassemblies for Inhibiting Amyloid Aggregates, Suppressing Microbial Infection, and Overcoming the Blood-Brain Barrier.

Amyloid aggregation, microbial infection, and the blood-brain barrier (BBB) are considered critical obstructions for the treatment of Alzheimer's disease (AD). At present, existing treatment strategies are rarely able to overcome these critical factors. Herein, we propose an innovative treatment strategy and design multifunctional nanoassemblies (yCDs-Ce6) from coassembling photosensitizers (chlorine e6) and yellow fluorescent carbon dots, which endow yCDs-Ce6 with the functions for photodynamic and photothermal therapy (PDT and PTT). Compared with reported inhibitors, yCDs-Ce6 can suppress amyloid aggregation for 7 days, disaggregate aggregates, reduce amyloid aggregation-induced cytotoxicity, and prevent microbial growth by PDT and PTT. Moreover, yCDs-Ce6 can specifically target amyloid aggregates and visually label amyloid aggregates. yCDs-Ce6 can also cross the BBB upon near-infrared light irradiation and clear amyloid deposition in APP/PS1 mice by PDT and PTT. Meanwhile, yCDs-Ce6 did not cause significant negative effects on normal cells or tissues. Based on the methods of PPT and PTT treatment, the research deeply explores the effect of the novel nanoassemblies on two hypotheses of AD, opening a novel therapeutic paradigm for research amyloid-related diseases.

Curcumin-loaded protein imprinted mesoporous nanosphere for inhibiting amyloid aggregation.

Some natural variants of human lysozyme are associated with systemic non-neurological amyloidosis that leads to amyloid protein fibril deposition in different tissues. Inhibition of amyloid fibrillation by nanomaterials is considered to be an effective approach to treating amyloidosis. Here, we prepared a targeted, highly loaded curcumin lysozyme-imprinted nanosphere (CUR-MIMS) that could effectively inhibit the aggregation of lysozyme with lysozyme adsorption capacity of 193.57 mg g-1 and the imprinting factor (IF) of 3.72. CUR-MIMS could bind to lysozyme through hydrophobic interactions and effectively reduce the hydrophobicity of the total solvent-exposed surface in lysozyme fibrillation, thus reducing the self-assembly process triggered by hydrophobic interactions. Thioflavin T (ThT) analysis demonstrated that CUR-MIMS inhibited the aggregation of amyloid fibrils in a dose-dependent manner (inhibition efficiency of 56.07 %). Circular dichroism (CD) spectrum further illustrated that CUR-MIMS could significantly inhibit the transition of lysozyme from α-helix structure to ß-sheet. More importantly, biological experiments proved the good biocompatibility of CUR-MIMS, which indicated the potential of our system as a future therapeutic platform for amyloidosis.

Structural Remodeling Mechanism of the Toxic Amyloid Fibrillary Mediated by Epigallocatechin-3-gallate.

Numerous therapeutic agents and strategies were designed targeting the therapies of Alzheimer's disease, but many have been suspended due to their severe clinical side effects (such as encephalopathy) on patients. The attractiveness for small molecules with good biocompatibility is therefore restarted. Epigallocatechin-3-gallate (EGCG), extracted from green tea, is expected to be a promising small-molecule drug candidate, which can remodel the structure of preformed ß-sheet-rich oligomers/fibrils and then effectively interfere with neurodegenerative processes. However, as the structure of non-fibrillary aggregates cannot be directly characterized, the atomic details of the underlying inhibitory and destructive mechanisms still remain elusive to date. Here, all-atom molecular dynamics simulations and experiments were carried out to elucidate the EGCG-induced remodeling mechanism of amyloid ß (Aß) fibrils. We showed that EGCG was indeed an effective Aß fibril inhibitor. EGCG was capable of mediating conformational rearrangement of Aß1-42 fibrils (from a ß-sheet to a random coil structure) and triggering the disintegration of fibrils in a dose-dependent manner. EGCG redirected the structure of Aß by breaking the ß-sheet structure and hydrogen bonds between peptide chains within the Aß protofibrils, especially the parallel ß-strand (L17VFFAEDVGS26). Moreover, reduced solvent exposure and multisite binding patterns all tended to induce the conformation conversion of Aß17-42 pentameric protofibrils, destroying pre-formed fibrils and inhibiting continued fibril growth. Detailed data analysis revealed that structural features of EGCG with abundant benzene ring and phenolic hydroxyl moieties preferentially interact with the parallel ß-strands to effectually hinder the interaction of the interpeptide chain and the growth of the ordered ß-sheet structure. Furthermore, experimental studies confirmed that EGCG was able to disaggregate the preformed fibrils and alter the protein structure. This study will enable a deeper understanding of fundamental principles for design of structural-based inhibitors.

Advanced nanomaterials for modulating Alzheimer's related amyloid aggregation.

Alzheimer's disease (AD) is a common neurodegenerative disease that brings about enormous economic pressure to families and society. Inhibiting abnormal aggregation of Aß and accelerating the dissociation of aggregates is treated as an effective method to prevent and treat AD. Recently, nanomaterials have been applied in AD treatment due to their excellent physicochemical properties and drug activity. As a drug delivery platform or inhibitor, various excellent nanomaterials have exhibited potential in inhibiting Aß fibrillation, disaggregating, and clearing mature amyloid plaques by enhancing the performance of drugs. This review comprehensively summarizes the advantages and disadvantages of nanomaterials in modulating amyloid aggregation and AD treatment. The design of various functional nanomaterials is discussed, and the strategies for improved properties toward AD treatment are analyzed. Finally, the challenges faced by nanomaterials with different dimensions in AD-related amyloid aggregate modulation are expounded, and the prospects of nanomaterials are proposed.

Dual-targeted carbon-dot-drugs nanoassemblies for modulating Alzheimer's related amyloid-ß aggregation and inhibiting fungal infection.

Amyloid aggregation and fungal infection, especially amyloid beta (Aß) peptide and Candida albicans are considered as two of the crucial pathogenic agents in Alzheimer's disease (AD). In this work, we propose an innovative treatment strategy for AD, targeting at not only Aß aggregation but also Candida albicans infection. Here, a high-performance nanomaterial, namely gCDs-E, have been prepared by self-assembled of glycosylated carbon dots (gCDs) and epigallocatechin-3-gallate (EGCG). Surprisingly, gCDs-E can not only suppress the fibrillation of Aß and disaggregate Aß fibrils, but also effectively inhibit the activity of Candida albicans. More importantly, the prepared gCDs-E can effectively cut down the cytotoxicity of amyloid aggregations, and the cell viability reached to 99.2%. In addition, the capability of the gCDs-E for blood brain barrier (BBB) penetration was also observed using a normal mice model. Above all, the gCDs-E greatly cleaned Aß deposition and improved memory impairment in APP/PS1 transgenic AD model mice, confirming its potential as therapeutic agent for AD treatment.

Chitosan modified ultra-thin hollow nanoparticles for photosensitizer loading and enhancing photodynamic antibacterial activities.

Antibacterial photodynamic therapy (PDT) has attracted extremely attention due to not inducing bacteria to generate resistance. However, the poor utilization and low reactive oxygen species (ROS) field of photosensitizers hinder their further application for antibacterial. Here, we designed ultra-thin hollow silica nanoparticles (UHSN), followed by pore-engineering including covalent anchoring of chitosan (UHSN@CS) for enhanced loading and photodynamic property of photosensitizer. The UHSN@CS exhibit high loading efficiency (80.6%, pH = 6.0) and controllable pH-responsive release for Ce6. Additionally, UHSN@CS can enhance the ROS yield of photosensitizers and effectively adhere to S. aureus, thus enormously enhancing antibacterial performance toward bacteria. Moreover, UHSN@CS-Ce6 can obliterate mature S. aureus biofilm and cause an 81% decrease in the biomass, showing a better therapeutic effect than Ce6 (59.2%) under laser irradiation. In vivo results confirm that UHSN@CS-Ce6 is effective to promote infectious wound regeneration. As photodynamic-based nanoplatforms, UHSN@CS-Ce6 are potential antibacterial agents for skin infection therapy.

Amino acid-functionalized carbon quantum dots for selective detection of Al3+ ions and fluorescence imaging in living cells.

Carbon quantum dots (CQDs) are drawing tremendous attention due to their unique photoluminescence property and fascinating functions. Herein, we prepared novel CQDs functionalized with amino acids (AA-CQDs) by a one-pot hydrothermal method for selective detection of Al3+ ions and fluorescence imaging. The prepared AA-CQDs exhibit a novel triple-excitation and single-colour emission for fluorescent property. In addition, the AA-CQDs have a high absolute quantum yield (24.23%) and quantum lifetime (13.29 ns). Moreover, the AA-CQDs exhibit high selectivity and sensitivity for Al3+ by fluorescence enhancement. In pH 7.4 PBS solution, there was a good linear relation between the fluorescence intensity and the concentration of Al3+ in the range of 1-20 µmol L-1; the limit of detection (3σ) was only 0.32 µmol L-1. Furthermore, an AA-CQD probe was also utilized for detection of Al3+ in living cells based on excellent biocompatibility and endocytosis. Based on the concentration of Al3+ ions in cells and apoptosis data, there will be a quick reflect of apoptosis induced by aluminium ions via the fluorescence intensity of the AA-CQD probe. This work will set the stage for developing novel CQD-based biosensors in cell research.

Lasting Tracking and Rapid Discrimination of Live Gram-Positive Bacteria by Peptidoglycan-Targeting Carbon Quantum Dots.

Selective discrimination and lasting tracking of live bacteria are primary steps for microbiology research and treatment of bacterial infection. However, conventional detection methods, such as the gold standard of Gram staining, are being challenged under actual test conditions. Herein, we provided a novel method, namely, three excitation peaks and single-color emission carbon quantum dots (T-SCQDs) for the rapid (5 min) peptidoglycan-targeting discrimination of Gram-positive bacteria and lasting tracking (24 h) through one-step staining. Bacterial viability testing indicates that T-SCQDs can achieve nondestructive identification of Gram-positive bacteria within 50-500 µg mL-1. Interestingly, the fluorescence imaging system suggests that T-SCQDs can also selectively distinguish the type of colonies based on fluorescence intensity. Furthermore, T-SCQDs were successfully used to visually distinguish Gram-positive bacteria from the microbial environment of A549 cells by confocal fluorescence microscopy. These properties endow T-SCQDs with excellent functions for the diagnosis of infection and other biological applications.

pH responsive superporogen combined with PDT based on poly Ce6 ionic liquid grafted on SiO2 for combating MRSA biofilm infection.

Background: Biofilm infection caused by multidrug-resistant bacteria is difficult to eradicate by conventional therapies. Photodynamic therapy (PDT) is an effective antibacterial method for fighting against biofilm infection. However, the blocked photosensitizers outside of biofilm greatly limit the efficacy of PDT. Methods: Herein, a novel acid-responsive superporogen and photosensitizer (SiO2-PCe6-IL) was developed. Because of the protonation of the photosensitizer and the high binding energy of the polyionic liquid, SiO2-PCe6-IL changed to positive SiO2-PIL+ in an acidic microenvironment of biofilm infection. SiO2-PIL+ could combine with negatively charged extracellular polymeric substances (EPS) and create holes to remove the biofilm barrier. To strengthen the interaction between SiO2-PIL+ and EPS, SiO2-PIL+ of high charge density was prepared by grafting the high-density initiation site of ATRP onto the surface of the SiO2 base. Results: Due to the rapid protonation rate of COO- and the strong binding energy of SiO2-PIL+ with EPS, SiO2-PCe6-IL could release 90% of Ce6 in 10 s. With the stronger electrostatic and hydrophobic interaction of SiO2-PIL+ with EPS, the surface potential, hydrophobicity, adhesion and mechanical strength of biofilm were changed, and holes in the biofilm were created in 10 min. Combining with the release of photosensitizers and the porous structure of the biofilm, Ce6 was efficiently concentrated in the biofilm. The in vitro and in vivo antibacterial experiments proved that SiO2-PCe6-IL dramatically improved the PDT efficacy against MRSA biofilm infection. Conclusion: These findings suggest that SiO2-PCe6-IL could rapidly increase the concentration of photosensitizer in biofilm and it is an effective therapy for combating biofilm infection.

Drug-based magnetic imprinted nanoparticles: Enhanced lysozyme amyloid fibrils cleansing and anti-amyloid fibrils toxicity.

Lysozyme amyloid fibrils, the misfolding structures generated from natural state of lysozyme, are found to be related with non-neuropathic systemic amyloidosis. Therefore, inhibiting the formation of amyloid and disaggregating amyloid fibers are both effective strategies. Herein, we present a combination of Epigallocatechin-3-gallate (EGCG), imprinting technology and magnetic nanoparticles to obtain a kind of promising nanomaterials (MINs@EGCG) for amyloid inhibition, drug carrier and facile separation triple functions. We declared the efficacy of MINs@EGCG from two perspectives. For inhibition, Circular dichroism (CD) spectrum illustrated that the miss transition from α-helix structure to ß-sheet could be blocked by MINs@EGCG, and the inhibition efficiency was higher than 80%. These results were further verified by Thioflavin T (ThT) analysis. For disaggregation and cleansing, the helical and highly periodic structure of amyloid fibrils could be converted into their counterparts by MINs@EGCG. Furthermore, with the aid of external magnetic field, the cleansing efficiency of counterparts-MINs@EGCG complex was up to 80%. Most importantly, bio-related experiments showed superior biocompatibility and anti-amyloid fibrils toxicity of MINs@EGCG, indicating the great potential of our system to work as an effective amyloidosis therapy platform.

Molecularly Imprinted Materials for Selective Biological Recognition.

Molecular imprinting is an approach of generating imprinting cavities in polymer structures that are compatible with the target molecules. The cavities have memory for shape and chemical recognition, similar to the recognition mechanism of antigen-antibody in organisms. Their structures are also called biomimetic receptors or synthetic receptors. Owing to the excellent selectivity and unique structural predictability of molecularly imprinted materials (MIMs), practical MIMs have become a rapidly evolving research area providing key factors for understanding separation, recognition, and regenerative properties toward biological small molecules to biomacromolecules, even cell and microorganism. In this review, the characteristics, morphologies, and applicability of currently popular carrier materials for molecular imprinting, especially the fundamental role of hydrogels, porous materials, hierarchical nanoparticles, and 2D materials in the separation and recognition of biological templates are discussed. Moreover, through a series of case studies, emphasis is given on introducing imprinting strategies for biological templates with different molecular scales. In particular, the differences and connections between small molecular imprinting (bulk imprinting, "dummy" template imprinting, etc.), large molecular imprinting (surface imprinting, interfacial imprinting, etc.), and cell imprinting strategies are demonstrated in detail. Finally, future research directions are provided.