Phenylboronic Acid-Modified Gold Nanoclusters as a Nanoantibiotic to Treat Vancomycin-Resistant Enterococcus faecalis-Caused Infections.

Vancomycin is one of the last lines of defense against certain drug-resistant bacteria-caused infections. However, the high susceptibility to drug resistance and high toxicity seriously limit the application of vancomycin. Nanoantibiotics provide opportunities to solve these problems. Herein, we present mercaptophenylboronic acid (MBA)-modified gold nanoclusters with well-defined molecular formulas and structure (Au44(MBA)18) and excellent antibacterial activities against various drug-resistant bacteria such as vancomycin-resistant Enterococcus faecalis (VRE). Au44(MBA)18 interacts with bacteria by first attaching to teichoic-acid and destroying the cell wall and subsequently binding to the bacterial DNA. Au44(MBA)18 could be administered via multiple routes and has a high biosafety (500 mg/kg, no ototoxicity), overcoming the two major shortcomings of vancomycin (sole administration route and high ototoxicity). Our study is insightful for curing infections caused by multidrug-resistant bacteria using nanoantibiotics with high biosafety.

Home quarantine during COVID-19 blunted childhood trauma-related psychiatric symptoms in Chinese college students.

Background: Childhood trauma confers risks to mental health. However, little is known about whether home quarantine (HQ) during the coronavirus disease 2019 (COVID-19) pandemic exaggerated or mitigated the effect of childhood trauma on mental health. Objective: To examine the modulating effects of prior childhood traumas on the longitudinal changes of psychiatric symptoms in college students before and after HQ during the pandemic. Methods: This was a two-wave longitudinal study on the mental health of 2,887 college students before and after HQ during the COVID-19 pandemic. The relationships between the changes in the Patient Health Questionnaire-9 (PHQ-9), Symptom Checklist-90 (SCL-90), 16-item Prodromal Questionnaire (PQ-16), Childhood Trauma Questionnaire (CTQ), and Social Support Rating Scale (SSRS) scores were analyzed. Results: The students with childhood trauma showed a significantly greater decrement in psychiatric symptoms after HQ (F = 17.21, 14.11, 18.87, and 17.42 for PHQ-9, PQ-16 objective and distress, and SCL-90, respectively). The correlation coefficients between the CTQ and these symptoms scales were significant at baseline (r = 0.42, 0.34, 0.37, and 0.39), and decreased after HQ (r = 0.17, 0.20, 0.18, and 0.19). The decrement of depressive, psychotic, and overall symptoms was positively correlated with the scores of the CTQ (r = 0.08-0.27) but negatively correlated with SSRS (r = -0.08--0.14). Multilinear regression analysis confirmed the results of the CTQ and SSRS regarding the modulation of the dynamic changes in psychiatric symptoms. A constructed structural equation model indicated that the total effects of childhood trauma on decreased psychiatric symptoms were partly mediated by lower baseline social support. Conclusion: Home quarantine during the COVID-19 pandemic could blunt the adverse effects of childhood trauma on mental health, especially for prodromal psychotic symptoms in college students. Changes in relative deprivation and social support may be mediating factors.

Dual targeting nanoparticles for epilepsy therapy.

For epilepsy therapy, one-third of the patients worldwide are resistant to antiepileptic drugs mainly due to the existence of the blood-brain barrier (BBB) that prevents the drugs from reaching the epileptic lesions. Here, we design a double targeting nanoparticle carrying lamotrigine (LTG) to cross the BBB and further concentrate at the neurons. We prepare the nanoparticles on a microfluidic chip by encapsulating LTG in poly(lactic-co-glycolic acid) (PLGA) to form a core (PL) and capping the core with a shell of lipids conjugated with the D-T7 peptide (targeting the BBB) and Tet1 peptide (targeting the neuron) to form D-T7/Tet1-lipids@PL nanoparticles (NPs). In vitro and in vivo experiments show that D-T7/Tet1-lipids@PL NPs have excellent neuron targeting, antiepileptic, and protecting effects. Our approach provides a new strategy for improving the therapeutic efficacy of existing antiepileptic drugs.

Breathable and Stretchable Dressings for Accelerating Healing of Infected Wounds.

Multidrug-resistant (MDR) bacteria-infected wounds are challenging issues that threaten human health. Herein, L-thioproline (T) and Boc-capped L-thioproline (BT)-decorated gold nanoparticles (TBT-GNPs) with potent antibacterial activity against MDR bacteria are reported. The TBT-GNPs are composited with bacterial cellulose to form wound dressings which show excellent antimicrobial performance both in vitro and in vivo. Moreover, this dressing is both breathable and stretchable which is favorable for gas exchange to accelerate the wound healing. This work is insightful for developing multifunctional dressings to satisfy the clinical requirements.

Modulating the antibacterial activity of gold nanoparticles by balancing their monodispersity and aggregation.

Aggregation is a key factor influencing the function of nanoparticles. Thioproline-modified gold nanoparticles show potent antibacterial activity, which is compromised by thioproline-mediated particle aggregation. By tuning the balance between the exposure and shielding of thioproline, a maximal antibacterial property of the gold nanoparticles is achieved.

Correction: Screening on-chip fabricated nanoparticles for penetrating the blood-brain barrier.

Correction for 'Screening on-chip fabricated nanoparticles for penetrating the blood-brain barrier' by Qinghong Hou et al., Nanoscale, 2022, DOI: 10.1039/d1nr05825h.

Screening on-chip fabricated nanoparticles for penetrating the blood-brain barrier.

The inability of drugs to cross the blood-brain barrier (BBB) makes it difficult to treat diseases in the central nervous system. It is known that peptides with or without specific receptors on the BBB showed different or even controversial neuron targeting capability in different reports. So, it is necessary to clarify how these peptides work as targeting molecules in the central nervous system. Herein, we evaluate and compare the performance of 6 kinds of peptides with (T7, D-T7, and GSH) or without (TGN, CGN, and TAT) BBB-specific receptors by conjugating these peptides on lipids to serve as a shell to encapsulate a core of PLGA and lamotrigine to form nanoparticles for targeted epilepsy therapy. In vitro assay shows that the TAT-modified nanoparticles show the highest internalization efficacy in the BBB model cell line bEnd·3 cells and hippocampal neurons. By contrast, experiments in mice show that the D-T7-modified nanoparticles have the highest brain targeting and epilepsy therapeutic efficiency. Thus, our experiments uncover the different performances of the 6 peptides at different levels (in vitro and in vivo), which is insightful for developing novel delivery systems for treating diseases in the central nervous system.

Bioeffects of Inhaled Nanoplastics on Neurons and Alteration of Animal Behaviors through Deposition in the Brain.

The potential toxicity of nanoplastics on plants has previously been illustrated, but whether nanoplastics could cause neurotoxicity, especially to higher animals, remains unclear. We now demonstrate that nanoplastics can be deposited in the brain via nasal inhalation, triggering neuron toxicity and altering the animal behavior. Polystyrene nanoparticles (PS-NPs) of PS-COOH and PS-NH2 are used as models for nanoplastics. We designed a microfluidic chip to evaluate the PS-NPs with different concentrations, surface ligands, and sizes to interact with neurons. Smaller PS-NPs can induce more cellular uptake than larger PS-NPs. PS-NPs with a size of 80 nm can reach and deposit in the brain of mice via aerosol inhalation. Mice inhaling PS-NPs exhibit fewer activities in comparison to those inhaling water droplets. An obvious neurotoxicity of the nanoplastics could be observed from the results of the inhibition of AChE activities. Our results show the potential significance of the physiochemical properties of organic nanoplastics on depositing in mammalian brains by nasal inhalation.

Fluorescent and Antibacterial Aminobenzeneboronic Acid (ABA)-Modified Gold Nanoclusters for Self-Monitoring Residual Dosage and Smart Wound Care.

The replacement of dressings may cause secondary damage to the wounds; thus, the real-time monitoring of the state of wound dressings is crucial for evaluating wound care processes. Herein, we report a smart dressing to self-monitor residue nanomedicine on it during the application. We load aminobenzeneboronic acid (ABA)-modified gold nanoclusters (A-GNCs) on bacterial cellulose (BC) membranes as an antibacterial wound dressing to display the amount of residual nanomedicine (A-GNCs) by in situ colorimetry during the application in remedying multi-drug-resistant (MDR) bacteria-infected wounds. A-GNCs emit bright orange fluorescence under UV light, whereas the BC membrane is transparent at a humidified state on the wounds. Thus, the BC-A-GNCs nanocomposite (BGN) shows decreasing intensity of orange fluorescence with the release of the A-GNCs, indicating the appropriate time points for the replacement of the dressing. The BGN, which can realize accurate self-monitoring in a simple, low-cost, and efficient way, thus holds great promise for broad clinical applications.

Integrating a Concentration Gradient Generator and a Single-Cell Trapper Array for High-Throughput Screening the Bioeffects of Nanomaterials.

We herein develop a concentration gradient generator (CGG) on a microfluidic chip for diluting different nanoparticles. Specifically designed compact disk (CD)-shaped microchannels in the CGG module could thoroughly mix the flowing solutions and generate a linear concentration gradient of nanoparticles without aggregation. We combine the CGG with a single-cell trapper array (SCA) on microfluidics to evaluate the concentration-dependent bioeffects of the nanoparticles. The precise control of the spatiotemporal generation of nanoparticle concentration on the CGG module and the single-cell-level monitoring of the cell behaviors on the SCA module by a high-content system in real time, render the CGG-SCA system a highly precise platform, which can exclude the average effect of cell population and reflect the response of individual cells to the gradient concentrations accurately. In addition, the CGG-SCA system provides an automated platform for high-throughput screening of nanomedicines with high precision and low sample consumption.

Mercaptophenylboronic Acid-Activated Gold Nanoparticles as Nanoantibiotics against Multidrug-Resistant Bacteria.

Multidrug-resistant (MDR) bacteria-induced infections are becoming challenging issues threatening human health and life. Current antibiotics can hardly tackle this problem. Herein, we present a strategy to prepare mercaptophenylboronic acid (MBA)-activated gold nanoparticles (Au NPs) as an antibacterial agent against MDR bacteria. Both Au NPs and MBA cannot serve as antibiotics. However, when MBA attaches on Au NPs, the Au_MBA NPs show potent antibacterial activities against Gram-positive MDR clinical isolates (e.g., MDR Staphyloccocus aureus, MDR S. aureus; MDR Staphyloccocus epidermidis, MDR S. epidermidis). Furthermore, Au_MBA NPs show an extremely high median lethal dose (LD50,i.v., 960 mg/kg), which is much higher than those of most of the clinically used antibiotics. As an application example, we dope Au_MBA NPs with electrospun poly(ε-caprolactone) (PCL)/gelatin nanofibrous membranes as wound dressings, which show striking ability to remedy S. aureus- or MDR S. aureus-infected full-thickness skin wounds on rats. Our study provides a novel strategy for treating MDR bacteria-infected wounds in a simple, low-cost, and efficient way, which holds promise for broad clinical applications.