Latest ArticlesGlioma is the most common malignant tumor of the brain. The postoperative recurrence rate was high, and the 2-year survival rate only increased by 20%–25%. The reason is the blood-brain barrier (BBB). BBB is a physical barrier that stabilizes the physiological environment of brain tissue and protects the central nervous system from the invasion of harmful substances. Drug delivery based on nanotechnology and nanocarriers has attracted much attention due to its biological safety, continuous drug release time, increasing solubility, biological drug activity, and enhanced BBB permeability. By modifying different substances on the surface of nanocarriers, the BBB is bypassed by receptor-mediated and cell endocytosis and exocytosis. In addition, the purpose of bypassing BBB-targeted drug delivery can also be achieved by intranasal administration and local administration. This paper reviews different target transport mechanisms, mainly in invasive and non-invasive strategies, the nanocarriers that have made progress and the nanocarrier strategy of bypassing BBB are listed.
A highly sensitive zinc ion fluorescent probe NOD-NY with controlled release of nitric oxide was designed, synthesized and used for tracking intracellular zinc ions in living A549 cells. NOD-NY was prepared from naphthalimide as the fluorophore and N,N-bis(2-pyridylmethyl)amine as the zinc ion recognition receptor, the amide N atom of the naphthalimide was connected to n-butylamine. Under the irradiation of ultraviolet light, NOD-NY can quantitatively release nitric oxide and generate a highly sensitive zinc ion probe Zn-HN, accompanied by a red-shift process of maximum ultraviolet absorption from 350 nm to 450 nm. Upon addition of Zn2+ to the solutions of Zn-HN, a remarkable fluorescence enhancement was observed, which could be attributed to the photo-induced electron transfer (PET) mechanism. By replaced the n-butylamine on NOD-NY with diethylene glycolamine or triphenylphosphine structures, NOD-AY with good biocompatibility and NOD-BY that can target mitochondria were obtained respectively. In addition, the nitric oxide released by NOD-NY enriched in lysosome can diffuse into mitochondria. The released nitric oxide can stimulate metallothionein to release zinc ions, and the light-induced in situ generated zinc ion probe Zn-HN can have a highly sensitive fluorescence response to free zinc ions in living A549 cells.
The rapid emergence of drug-resistant bacterial strains undermines the efficacy of conventional antibiotics, necessitating the development of alternative therapies. Antimicrobial photodynamic therapy (PDT) is a promising approach, but its effectiveness is often limited by the suboptimal photocatalytic activity of photosensitizers. In this study, we introduce a novel photoresponsive carbon-based antibacterial agent, Ce6/g-C3N4, which combines the photocatalytic properties of graphite-phase carbon nitride (g-C3N4) with the photodynamic attributes of chlorin e6 (Ce6). This agent, with an average particle size of 250.7 nm, demonstrates significantly enhanced photocatalytic activity. Additionally, the strong affinity of Ce6/g-C3N4 for bacteria and efficient delivery of Ce6 result in an inhibition rate exceeding 99% against Gram-positive bacteria and excellent biofilm eradication under light irradiation. In vivo experiments reveal that Ce6/g-C3N4 effectively inhibits bacterial growth on wounds, and promotes wound healing post-light treatment, while maintaining good biocompatibility. Overall, the Ce6/g-C3N4 antibacterial agent synergizes photodynamic and photocatalytic mechanisms, offering a new avenue for the photo-mediated, multi-strategic treatment of bacterial infections and wound healing.
Molecular recognition of fullerene using various host compounds is well-known in literature. But most studies focus on host-guest complexation in solution using host compounds with a single binding cavity. Herein, we report a series of highly preorganized janusarene derivatives with homoditopic binding sites. These novel janusarenes can bind and align various fullerenes such as C60, C70, C84, and Gd@C82 in a highly efficient manner. Robust shape complementary association and assembly are observed in solution, in the bulk solid state, in the liquid crystalline state, or on surface, and the assembled structures are characterized by nuclear magnetic resonance (NMR) titration, X-ray diffraction, polarized optical microscopy, and scanning tunneling microscopy.
Wound healing in diabetic patients presents significant challenges due to heightened risks of bacterial infection, elevated glucose levels, and insufficient angiogenesis. Nanozymes are widely employed for wound healing, but most current nanozyme systems exhibit only moderate activity limited by incompatible reaction microenvironments including pH and hydrogen peroxide (H2O2) concentration. Herein, a glucose-activated nanozyme hydrogel was developed using bovine serum albumin (BSA)-modified gold nanoparticles (Au NPs) attached to a two-dimensional (2D) metal-organic framework (MOF) (Cu-TCPP(Fe)@Au@BSA) by an in situ growth method. The Au NPs function as a glucose oxidase (GOx)-like enzyme, converting glucose to gluconic acid and H2O2, triggering the peroxidase (POD)-like activity of Cu-TCPP(Fe) to produce hydroxyl radicals (•OH), effectively eliminating bacteria. Additionally, the modification of BSA reduces the Au NP size, enhancing enzyme activity. Both in vitro and in vivo tests demonstrate that this nanozyme hydrogel can be activated by the microenvironment to lower blood glucose, eliminate bacterial infections, and promote epithelial formation and collagen deposition, thus accelerating diabetic wound healing effectively. The multifunctional nanozyme hydrogel dressing developed in this study presents a promising therapeutic approach to enhance diabetic wound healing.
Photoheranostics have emerged as a promising tool for cancer theranostics owing to their real-time feedback on treatment and their precise diagnosis. Among them, how to improve the photothermal conversion efficiency (PCE) of phototheranostic agents (PTAs) is the key factor for phototheranostic systems. Herein, we provided an efficient method to improve PCE and constructed a biocompatible nano-material ICR-Qu@NH2-Fe3O4@PEG (QNFP) by combing near-infrared second region (NIR-Ⅱ) molecular dye ICR-Qu and amino-modified magnetic nanoparticles and then encapsulated by DSPE-mPEG2000. QNFP exhibited excellent performance for photothermal therapy with a high PCE of 95.6%. Both in vitro and in vivo experiments indicated that QNFP could inhibit the growth of tumors under laser irradiation with low toxicity and realized real-time NIR-Ⅱ fluorescent imaging of tumors. In general, we realized a simple but efficient method to improve the PCE of NIR-Ⅱ molecular dye without reduce its quantum yield, which is an ideal choice for cancer diagnosis and treatment.
Liquid-liquid phase separation (LLPS) of proteins and nucleic acids is a common phenomenon in cells that underlies the formation of membraneless organelles. Although the macroscopic behavior of biomolecular coacervates has been elucidated by microscopy, the detailed dynamic properties of proteins/peptides during the LLPS process remain poorly characterized. Here, site-directed spin labeling-electron paramagnetic resonance (SDSL-EPR) spectroscopy was employed to characterize the dynamic properties of a minimal model LLPS system consisting of positively charged peptides and RNA. The degree of phase separation, indicated by broadening of the EPR spectrum of the spin-labeled peptide due to slow molecular tumbling, was monitored by EPR. In addition, three distinct populations with varying molecular motion during LLPS, featuring different spectral lineshapes, were identified. These populations included a fast motion component (Ⅰ), a slower motion component (Ⅱ) associated with peptides in the dispersed phase and an immobile component (Ⅲ) observed in the dense phase. With gradual titration of the peptides to RNA, the EPR spectrum gradually shifted, reflecting changes in the populations of the components. Together, SDSL-EPR method not only provides new insights into the dynamic behavior of biomolecules during LLPS, but also offers a sensitive method for biomolecular phase separation processes at the molecular level.
A decomposable and sono-enzyme co-triggered nanoparticle (pTCP-CR NP) with “AND gate” logic was synthesized, combining a meso‑carboxyl-porphyrin-based sonosensitizer (5,10,15,20-tetrakis(carboxyl)porphyrin, TCP) and a thiophenyl-croconium (2,5-bis[(2-(2-(2-hydroxyethoxy)ethoxy)ethyl-4-carboxylate-piperidylamino)thiophenyl]-croconium, CR) via ester groups. TCP releases carbon monoxide (CO) under ultrasound (US) irradiation, offering both sonodynamic and gas therapy. CR decomposes into stronger reactive oxygen species (ROS) compared to oxygen-based radicals. The Förster resonance energy transfer (FRET) effect between TCP and CR inhibits ROS and CO generation until triggered by tumor cell overexpressed carboxylesterase (CEs). pTCP-CR NPs “AND gate” logic ensures activation only in the presence of both CEs and US, targeting tumor cells while safety in normal tissues. The ROS and CO generation abilities, as well as the releasing of SO4•− have been systemically examined. pTCP-CR can be thoroughly decomposed into low-toxic molecules post the treatment, showing the safety with negligible phototoxic reactions. In vivo anti-cancer therapy has been evaluated using mice bearing hepatocellular carcinoma.
Inspired by the light-dependent signal transduction in nature, we herein report a fully synthetic receptor AZO with the capacity of transmembrane signaling, working by photo-induced change of molecular conformation. Our receptor has an anchoring group, a rigid and photoresponsive transmembrane unit and a precatalyst tailgroup. After doping in lipid membranes, AZO is membrane anchored and the extended trans-isomer enables the tailgroup to bind with intravesicular Zn2+, thereby achieving enzyme activation and triggering downstream events (ester hydrolysis). However, the shortened cis-isomer pulls the tailgroup into lipids, thereby preventing the complexation and all transduction processes. Upon alternative irradiation of ultraviolet (UV) and visible light, the transduction process can be reversible switch between "ON" and "OFF", achieving light signal transduction. This study provides a new strategy for future design of artificial signal transduction receptors.
Plant bacterial diseases have inflicted substantial economic losses in global crop, fruit, and vegetable production. The conventional methods for managing these diseases typically rely on the application of antibiotics. However, these antibiotics often target the growth factors of the pathogenic bacteria, leading to the accumulation and emergence of drug-resistant strains, which exacerbates antibiotic resistance. Innovative methods are urgently needed to treat and prevent the toxicity caused by these pathogenic bacteria. Targeting virulence mechanisms in pathogens is a globally recognized and effective strategy for mitigating bacterial resistance. Type III secretion system (T3SS) serves as a crucial virulence determinant in Gram-negative pathogens, and its non-essentials for pathogen growth renders it an ideal target. Targeting the T3SS holds significant potential to alleviate selective pressure for resistance mutations in pathogens. Therefore, targeting T3SS in pathogenic bacteria, while preserving their growth, has emerged as a novel avenue for the development of antimicrobial drugs. In recent years, a multitude of small molecular inhibitors targeting T3SS have been identified. This article offers a comprehensive review of T3SS inhibitors in plant pathogens, while also presenting the latest research advancements in this research direction.
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