Neuroregeneration has drawn scientific attention due to its therapeutic potential for neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and traumatic brain injury (TBI). A major obstacle in delivering neuroregenerative and neuroprotective drugs is crossing the blood-brain barrier (BBB)-a selective, physiological barrier that protects the central nervous system (CNS) from circulating toxins and pathogens. While this protective role is essential for maintaining CNS homeostasis, it also limits therapeutic efficacy and increases the risk of systemic side effects due to off-target accumulation. To overcome these challenges, recent advances in nanoparticle engineering have focused on enhancing BBB transcytosis by employing biologically inspired surface modifications. In this review, we highlight three mechanistically distinct approaches: (1) transporter-mediated transcytosis (TMT), which uses glucose or amino acid conjugation; (2) receptor-mediated transcytosis (RMT) via ligands such as transferrin or angiopep-2; and (3) adsorptive-mediated transcytosis (AMT), utilizing cationic polymer coatings or cell-penetrating peptides (CPPs).

Epilepsy is one of the most common neurological disorders, with current antiepileptic drugs (AEDs) being ineffective in up to 30% of patients. Moreover, the therapeutic efficacy of existing AEDs is significantly limited by the blood-brain barrier (BBB). The neuropeptide Y2 receptor is a potential antiepileptic target, with NPY (3-36) acting as its selective agonist. GW2580, an inhibitor of the colony-stimulating factor 1 receptor, has neuroprotective potential. In this study, a novel nanocomposite, NPY@ZIF-RG, was synthesized by covalently conjugating NPY (3-36) onto the surface of GW2580-encapsulated nano-Zeolitic imidazolate framework-90 (ZIF-90) via a simple post-modification. The biosafety of NPY@ZIF-RG was evaluated in vitro and in vivo. The BBB permeability and its effects on neuroinflammation and neuronal excitability were assessed. The therapeutic efficacy of NPY@ZIF-RG was explored using immunohistochemistry, quantitative real-time polymerase chain reaction, and behavioral tests in a mouse model of kainic acid-induced acute epilepsy. The results indicated that NPY@ZIF-RG exhibited excellent biocompatibility and efficient BBB penetration. Furthermore, it exerted beneficial therapeutic effects by inhibiting microglia-mediated inflammation and reducing excitatory glutamate release. NPY@ZIF-RG alleviated hippocampal neuronal loss and cognitive dysfunction by co-delivering GW2580 and NPY (3-36), which exerted synergistic neuroprotective and anti-inflammatory effects. This study provides a promising nanocomposite drug-delivery system for the treatment of epilepsy.

Hydrogen synergistic therapy, an emerging and promising strategy in tumor treatment, has been bolstered by nanotechnology to establish a stable and multifunctional foundation for its implementation. Hydrogen-synergistic diagnostic and therapeutic nanoplatforms (HSDT-NPs), a novel type of tool for tumor treatment, integrate hydrogen therapy with various tumor diagnostic and therapeutic strategies, significantly enhancing the efficiency and specificity of tumor treatment, which is crucial for achieving precision therapy at the tumor site. The construction of HSDT-NPs relies on the design of hydrogen nanomaterials and the selection and assembly of synergistic units. Through HSDT-NPs, the synergistic effects between hydrogen therapy and other strategies are markedly enhanced, not only improving the efficacy of traditional therapies on tumors but also effectively protecting normal cells. Based on different material types, this study explores the construction strategies of HSDT-NPs. Subsequently, focusing on the collaborative treatment modes, it delves into the synergistic mechanisms of HSDT-NPs. Our work aims to offer new perspectives and innovative approaches for advancing cancer treatment based on hydrogen therapy research.

Ischemic stroke continues to be a leading cause of death and long-term disability worldwide. However, the clinical use of intravenous tissue plasminogen activator (tPA) is constrained by its rapid systemic clearance and the risk of hemorrhagic transformation (HT). In this study, we present an MMP-9-responsive PLGA-based nanocarrier (tPLGA) that enables thrombus-microenvironment triggered release of tPA. When combined with Bindarit, an inhibitor of the CCL2/CCR2 pathway, this strategy achieves both targeted thrombolysis and effective suppression of HT. In mouse thrombosis models, tPLGA mediated precise spatiotemporal tPA delivery, enhancing clot dissolution. Concurrent CCL2/CCR2 blockade reduced neutrophil infiltration, preserved blood-brain barrier (BBB) integrity, and prevented HT. Behavioral, histological, and biosafety assessments confirmed improved neurological recovery and translational potential. This work establishes a therapeutic platform integrating precision thrombolysis with immune modulation for a safer and more effective treatment of ischemic stroke.

Hepatocellular carcinoma (HCC) is one of the most severe malignancies in modern society, and is known as an "inflammatory tumor", rarely benefiting from immunotherapies. In the inflammatory microenvironment of precancerous HCC, immune cells and stromal cells are transformed from an anti-tumor type into a pro-tumor type by stimuli of different inflammatory factors, oxidative stress and key signaling pathways. This evolution fosters a profoundly immunosuppressive niche, culminating in T cell exhaustion and the failure of immune checkpoint inhibitors (ICIs), which are further limited by systemic adverse events and low response rates. Emerging nanotherapeutic strategies, designed to precisely target and remodel the HCC immune landscape, offer a promising avenue to overcome these limitations. This review analyzes the mechanistic links between inflammation-driven immune suppression and progression. We evaluate and categorize cutting-edge nanomedicine approaches designed to initiate immune responses, reverse immunosuppression, and liberate T cell function. Furthermore, we discuss current challenges in clinical translation, particularly those stemming from the physicochemical properties and in vivo behavior of nanocarriers, and proposed strategic directions for next-generation inflammation-targeted nanotherapeutic design, providing new perspectives for breaking the cycle of immune tolerance in HCC.

Multifunctional nanoplatforms that integrate both exogenous stimuli-induced mild photothermal therapy (mPTT) and endogenous stimuli-responsive chemodynamic therapy (CDT) have shown great potential for precise and safe cancer treatment. However, the effective interplay among nanoplatform components to enhance the synergistic effects of mPTT and CDT still suffers from distinct limitations during implementation. Here, we present a novel multifunctional nanoplatform, HCuS-DOX@ZIF-8-GOX (HDZG), rationally engineered to achieve self-augmented mPTT/CDT through cascade regulation under near-infrared (NIR) irradiation, effectively addressing these limitations. Upon accumulation at the tumor site, the synergistic effects of GOX-catalyzed glucose consumption by inhibiting the glycolytic pathway and Zn2+-induced mitochondrial dysfunction accelerated adenosine triphosphate (ATP) depletion, thereby suppressing heat shock protein (HSP) expression and amplifying the efficacy of NIR-triggered mPTT. Simultaneously, reactive oxygen species (ROS) production was markedly amplified via an accelerated Fenton-like reaction, driven by elevated intracellular H2O2 levels produced from GOX-catalyzed glucose oxidation and the photothermal effect of hollow copper sulfide (HCuS). Moreover, glutathione (GSH) depletion was intensified by DOX-induced ROS production and the Cu+/Cu2+ cycling reaction, collectively contributing to a markedly improved CDT effect. Consequently, HDZG NPs demonstrated self-enhanced antitumor effects through NIR-induced mild photothermal/chemodynamic synergistic therapy, offering a promising strategy to improve the efficacy of multimodal cancer treatments.

Correction for 'Ciprofloxacin-loaded bioadhesive hydrogels for ocular applications' by Islam A. Khalil et al., Biomater. Sci., 2020, 8, 5196-5209.

Chronic wounds have emerged as a major healthcare challenge due to their prolonged healing cycle. A key feature of chronic wounds is local tissue hypoxia, resulting in insufficient oxygenation of the wound microenvironment. While traditional therapies like hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT) alleviate wound hypoxia by oxygen supplementation, they are limited by high costs, uncertainty in sustained efficacy, and complications, restricting clinical use. Oxygen carriers, such as perfluorocarbons (PFCs) and hemoglobin (Hb), exhibit high-efficiency oxygen delivery capacity, excellent biocompatibility and cost-effectiveness. They hold enormous potential for clinical applications. This review focuses on the application of PFCs and Hb-based oxygen carriers in chronic wound therapy. It systematically elaborates on the diversified oxygen delivery strategies based on PFCs and Hb. It also quantitatively compares their oxygen delivery capabilities and analyzes their multiple synergistic biological effects. Meanwhile the review also describes the difficulties and challenges in precise delivery and clinical translation.

Effective delivery of small interfering RNA (siRNA) to the cytosol continues to pose a significant challenge in RNA interference (RNAi)-driven precision cancer therapy. In this study, we engineered glutathione (GSH)-responsive bola-amphiphilic peptide dendrimers (bola DS-Cn-K4) for tumor-specific cytosolic siRNA delivery. These dendrimers incorporate a hydrophilic polylysine dendron for efficient siRNA binding and a hydrophobic disulfide-bridged bola-lipid core with varying alkyl chain lengths, facilitating thiol-mediated cellular uptake and enabling siRNA release in response to intracellular higher GSH levels. Our structure-activity relationship studies revealed that bola DS-C6-K4, characterized by the shortest alkyl chain, exhibited superior siRNA delivery, which was attributed to optimized thiol-mediated cellular uptake and accelerated GSH-triggered siRNA release stemming from improved disulfide accessibility. Mechanistic investigations validated thiol-mediated uptake as the predominant cellular internalization pathway, effectively bypassing endosomal entrapment. The siRNA/bola DS-C6-K4 complexes efficiently downregulate oncoprotein expression, thereby impeding cancer cell proliferation, migration, and invasion, and simultaneously inducing apoptosis. In A549 xenograft models, intravenous administration of siPLK1/bola DS-C6-K4 achieved substantial reductions in tumor growth and PLK1 expression while exhibiting minimal systemic toxicity. This study highlights a synergistic approach utilizing bola-amphiphilic peptide dendrimers for tumor-specific and cytosolic siRNA delivery, leveraging membrane-thiol interactions and intracellular GSH-triggered siRNA release.

Nowadays, with the growing need for alternative antibacterial materials for the treatment of bacterial infections, TiO2 with antibacterial properties has attracted attention as a potential antibacterial agent. Ni-TiO2 and Co-TiO2 nanofibers (NFs) were synthesized via an electrospinning process. The antibacterial activities of these NFs against S. aureus and E. coli were evaluated under UV-light illumination using optical density measurements. Co-TiO2 exhibited superior antibacterial activity against both S. aureus and E. coli under UV-light irradiation. The antibacterial mechanism was further investigated through a glutathione (GSH) oxidation assay and morphological analysis using scanning electron microscopy (SEM). Hydrophilicity was evaluated by contact angle measurement. The antibiofilm activities of TiO2, Ni-TiO2, and Co-TiO2 NFs were investigated with respect to E. coli and S. aureus biofilms. Ni-TiO2 and Co-TiO2 demonstrated more effective antibiofilm activities than bare TiO2. Under UV-light irradiation, the biofilm inhibition efficacy was increased for both Ni-TiO2 and Co-TiO2 NFs while Co-TiO2 NFs were found to have the greater antibiofilm performance. Additionally, in silico analysis was conducted to explore the molecular interactions of the NFs with S. aureus Immunoglobulin-Binding B Domain (PDB ID: 1BDD) and FimH lectin protein of E. coli (PDB ID: 4XO8). Co-TiO2 exhibited stronger binding to S. aureus, while TiO2 showed stronger binding to E. coli.