Liposomes

Staphylococcus aureus is a leading cause of nosocomial implant-associated infections, causing significant morbidity and mortality, underscoring the need for rapid, non-invasive, and cost-effective diagnostics. Here, we optimise the synthesis of renal-clearable gold nanoclusters (AuNCs) for enhanced catalytic activity with the aim of developing a sensitive colourimetric diagnostic for bacterial infection. All-atom molecular dynamics (MD) simulations confirm the stability of glutathione-coated AuNCs and surface access for peroxidase-like activity in complex physiological environments. We subsequently develop a biosensor by encapsulating these optimised AuNCs in bacterial toxin-responsive liposomes, which is extensively studied by various single-particle techniques. Upon exposure to S. aureus toxins, the liposomes rupture, releasing AuNCs that generate a colourimetric signal after kidney-mimetic filtration. The biosensor is further validated in vitro and in vivo using a hyaluronic acid (HA) hydrogel implant infection model. Urine samples collected from mice with bacteria-infected HA hydrogel implants turn blue upon substrate addition, confirming the suitability of the sensor for non-invasive detection of implant-associated infections. This platform has significant potential as a versatile, cost-effective diagnostic tool.

Combination therapy integrating chemotherapeutic agents with natural bioactive ingredients represents an attractive strategy for esophageal squamous cell carcinoma (ESCC) treatment, yet achieving tumor-specific co-delivery remains a critical challenge. Herein, we report that the combination of luteolin (LUT) and paclitaxel (PTX) exerts a remarkable synergy in ESCC treatment, while concurrently alleviating PTX-induced hepatotoxicity; EA2 aptamer has been identified for its exceptional specificity and strong affinity toward Catenin Alpha 1 protein (CTNNA1) in ESCC cells. Leveraging this specificity, nanosized EA2-modified pH-sensitive liposomes (EA2-PSL-PTX/LUT) are successfully developed with effective co-loading, controlled release, and good biostability. EA2-PSL-PTX/LUT exhibits stimuli-triggered release in the acidic tumor microenvironment and facilitates specific cellular uptake and endosomal escape in ESCC cells. In vivo imaging confirms precise tumor localization, deep tumor penetration, and prolonged retention of the nanocarrier. In vitro and in vivo findings validate that the nanocarrier potentiates synergistic inhibitions of PTX and LUT. Notably, EA2-PSL-PTX/LUT significantly activates the tumor microenvironment by promoting dendritic cell maturation and T cell infiltration. And the immunosuppressive microenvironment has been remodeled by decreasing myeloid-derived suppressor cells and regulatory T cell accumulation. This study provides a strategy for precise delivery of combinational chemotherapeutic drugs for ESCC targeted therapy.

Gouty arthritis is characterized by an acute inflammatory response triggered by monosodium urate (MSU) crystals deposited in the joints and periarticular tissues. Current treatments bring little effects owing to serious side effects, necessitating the exploration of new and safer therapeutic options. Macrophages play a critical role in the initiation, progression, and resolution of acute gout, with the cellular profiles closely linked to their activation and polarization. This suggests that metabolic regulation can be of significance in managing gouty inflammation. In this study, it is demonstrated that melatonin, a natural hormone, modulates the metabolic remodeling of inflammatory macrophages by shifting their metabolism from glycolysis to oxidative phosphorylation, further altering functions of the pathogenic macrophage. To improve melatonin delivery to the inflamed sites, macrophage membrane-coated melatonin-loaded liposomes (MLT-MLP) are developed. Benefiting from the inflammation-homing characteristic of macrophage membrane, such engineered liposomes effectively target the inflamed site and demonstrate potent anti-inflammatory effects, achieving an enhanced amelioration of acute gouty arthritis. In conclusion, this study proposes a novel strategy aimed at metabolic reprogramming of macrophages to attenuate the pathological injuries in acute gout, providing a potential therapeutic strategy of gout-associated diseases, especially gouty arthritis.

Background: Melanoma management faces the dual challenge of preventing tumor recurrence while ensuring optimal post-surgical wound healing, particularly problematic given melanoma's high recurrence rates and therapeutic resistance. Artesunate (ARS) emerges as a promising multimodal agent with concurrent anticancer, anti-inflammatory, and tissue-regenerative properties. However, its anti-melanoma mechanisms remain incompletely characterized, and clinical translation has been limited by suboptimal pharmacokinetics. Methods: We employed transcriptomic profiling (RNA-seq) to identify novel ARS-regulated pathways. Subsequently, we developed an optimized drug delivery system comprising: amphiphilic nanoliposomes for efficient ARS encapsulation and enhanced cellular internalization, and a carboxymethyl chitosan hydrogel matrix (ARS-LS-Gel) engineered to provide sustained drug release while promoting tissue regeneration. Comprehensive physicochemical characterization preceded systematic in vitro evaluation in melanoma (B16F10, A375) and normal cell models, assessing cytotoxicity, cellular uptake, and mechanistic pathways. Dual efficacy was quantified in vivo using syngeneic melanoma and full-thickness wound healing models. Results: The ARS-LS-Gel system demonstrated optimal physicochemical characteristics, including well-dispersed particles, sustained drug release kinetics and exceptional biocompatibility. It potently induced melanoma cell apoptosis through p53-mediated mitochondrial dysfunction, characterized by: (1) sustained ROS accumulation, (2) cytochrome C release, (3) mitochondrial membrane potential collapse, (4) impaired ATP synthesis, and (5) calcium overload. In vivo, the platform significantly suppressed tumor progression, evidenced by enhanced apoptosis and reduced Ki-67 expression. Concurrently, it accelerated wound regeneration via targeted downregulation of pro-inflammatory mediators (TNF-α, IL-1β) and enhanced collagen deposition. Conclusion: The ARS-LS-Gel platform's ability to simultaneously address oncogenic progression and tissue repair represents a significant conceptual and practical advancement in post-surgical cancer management. By bridging fundamental mechanistic discovery with engineered therapeutic delivery, our findings provide a robust foundation for imminent translational development in melanoma therapy and beyond.