Colloids and Surfaces B: Biointerfaces最新文献

To overcome the systemic toxicity and poor tumor targeting of the TLR7/8 agonist R848, this study developed a derivative by attaching a phenylboronic acid (PBA) group to R848. The resultant R848-PBA retain the immune activation of R848, easily assembly with indocyanine green (ICG) into nanoparticles (R-P@ICG NPs), which demonstrated greatly improved safety and excellent tumor targetability. Inspired by this, paclitaxel (PTX) was also conjugated with PBA and self-assembly with chlorogenic acid (CA) into nanoparticles (P-P@CA NPs). In 4T1 tumor mice mode, P-P@CA NPs induced significant immunogenic cell death (ICD) to release damage-associated molecular patterns (DAMPs) while R-P@ICG NPs synergistically promoted dendritic cells (DCs) maturation and trigger both innate and adaptive immune responses. This combined therapy achieved a tumor inhibition rate of 93.2 % and a tumor eradication rate of 33.3 %, accompanied by a long-lasting anti-tumor immune memory and no evident toxic effect. Phenylboronic acid modification and self-assembly with small molecules presents a promising strategy to realize the clinical translation of the synergistic antitumor efficacy of R848-based chemoimmunotherapy and chemotherapeutics by alleviated systemic toxicity and endowed tumor targetability.

Dental erosion, the chemical dissolution of the tooth surface structures, is an increasing problem in the modern world due to growing trends toward acidic food consumption and can cause permanent dental hard tissue loss. A detailed understanding of the reactivity of dental surfaces to chemicals invading the oral cavity is necessary to devise effective countermeasures. We introduce the use of converged roughness parameters Sq_conv, i.e., roughness parameters calculated at a reduced field of view, to reflect the critical surface building blocks controlling the reactivity, as measured by white light vertical scanning interferometry. By analyzing Sq_conv maps and their histograms, we gain detailed spatiotemporal insights into the surface alterations during processes such as acidic tooth demineralization and remineralization of eroded dental surfaces, harnessing the potential of readily available, easy-to-apply Ca caseinate. Furthermore, the impact of fluoridation on the dental surface reactivity is investigated. We find that the reactivity of the dentine surface is inherently inhomogeneous, with rough surface features being more reactive to erosion/demineralization, remineralization, and fluoridation. Our data reveal that de- and remineralization are mechanistically reversible processes, and both are potentially inhibited by surface fluoridation. However, this can be avoided by utilizing fluoride addition during Ca caseinate remineralization in a combined approach to build up new material that is more resistant to acidic impact. We demonstrate that the growth of biomimetic hydroxyapatite during remineralization occurs at a rate 3 orders of magnitude slower than the demineralization.

The osteomyelitis induced by methicillin-resistant Staphylococcus aureus (MRSA) remains a formidable clinical challenge due to persistent bacterial infection, chronic inflammation, and impaired bone regeneration. Herein, a multi-functional nanoplatform is prepared by manganese-based porphyrinic metal-organic frameworks (PCN-222(Mn)) modified with curcumin (Cur) for treating bacterial osteomyelitis. The resulting PCN-222(Mn)-Cur nanoparticles exhibit effective sonodynamic antibacterial activity by rapid reactive oxygen species generation, which also has a synergistic effect (antimicrobial rate of 99.98 %) with long-term antibacterial efficiency of curcumin. Besides, the effective cascade anti-oxidation reaction of PCN-222(Mn) can be achieved by superoxide dismutase- and catalase-like activities owing to the MnN₄ active site. In a rat tibial osteomyelitis model, compared with antibiotic therapy, the ultrasound-activated PCN-222(Mn)-Cur platform exhibits superior antibacterial efficacy against MRSA, coupled with synergistic anti-inflammatory effects and promoted osteogenic regeneration capacity. In summary, this biosafe nanoplatform demonstrates excellent bacterial-killing, anti-inflammation, and osteogenesis, offering a prospect for treating refractory bacterial bone infections.

Age-related macular degeneration (AMD) that leads to degeneration of the overlying photoreceptor in the macula and consequent loss of central vision is the leading cause of irreversible blindness in elderly population. Since vascular endothelial growth factor (VEGF) is pivotal for stimulating neovascularization, monthly intravitreal (IVT) injections of anti-VEGF agents have been used for eliminating neovascularization. However, repeated monthly IVT injections could cause side effects and serious complications. Herein, we report the development of two kinds of anti-VEGF agents (Ranibizumab (Ran) and Aflibercept (Afl))-loaded hollow mesoporous silica nanoparticles for effective treatment of AMD. The designed nanoparticles show no toxicity for both in vitro and in vivo, and could significantly inhibit VEGF-induced proliferation and cell migration. Long-term in vivo experiments in the laser photocoagulation induced choroidal neovascularization (CNV) model for wet AMD show that these nanoparticles effectively inhibit VEGF-induced neovascularization leakage and formation at least 8 weeks upon one IVT injection and therefore are a promising treatment strategy for AMD.

Alcohol dehydrogenase (ADH) is a key enzyme in ethanol metabolism and is abundant in pig liver, an underutilized animal by-product. Here, ADH was isolated from pig liver using aqueous two-phase extraction, and its enzymatic properties, structural characteristics, and biological relevance were systematically evaluated. The extracted ADH showed optimal activity at 45°C and pH 8.5, and its activity was enhanced by K⁺ and Mn²⁺. Spectroscopic analyses indicated overall structural similarity to yeast-derived ADH, while revealing a more ordered secondary structure with higher α-helix content. Kinetic analysis toward ethanol suggested a moderate catalytic efficiency relative to commercial yeast ADH, consistent with the physiological role of liver ADH in ethanol metabolism. MALDI-TOF/TOF mass spectrometry combined with bioinformatic analyses (GO enrichment and DisGeNET) supported associations with alcohol-related liver disease pathways. Molecular docking, molecular dynamics simulations, and density functional theory calculations predicted stable ethanol binding in proximity to the catalytic Zn²⁺ center. For biological validation, an ethanol-induced HepG2 cell injury model was established, showing that pig liver ADH mitigated ethanol-induced cytotoxicity by improving cell viability, suppressing intracellular ROS accumulation, reducing lipid peroxidation, and preserving glutathione homeostasis. Furthermore, liposomal encapsulation (ADH-LIPS) largely preserved catalytic activity while enhancing physicochemical stability, sustained release behavior, storage stability, and resistance to simulated gastrointestinal digestion. Overall, this work demonstrates the feasibility of recovering biologically relevant ADH from pig liver by-products and supports liposomal formulation as an effective strategy to improve enzyme stability under application-relevant constraints.

The pathological process of atherosclerosis (AS) is driven by the complex interplay of dyslipidemia, oxidative stress, and chronic inflammation, wherein the "inflammation-lipid" vicious cycle between macrophages and vascular smooth muscle cells (VSMCs) accelerates plaque progression and rupture. Traditional monotherapies are often insufficient to address these intertwined pathological drivers, underscoring the need for the development of multi-targeted therapeutic strategies. In this context, Prussian blue nanoparticles (PBs) are an ideal candidate for integrated therapy, featuring a hollow mesoporous structure, high photothermal conversion efficiency, and intrinsic enzyme-mimicking activity, providing a multifunctional "all-in-one" scaffold for drug delivery and reactive oxygen species (ROS) scavenging. In this study, we synthesized mesoporous PBs via a hydrothermal method and functionalized their surfaces with polyethyleneimine (PEI) to facilitate drug loading and subsequent modification. The lipid-lowering agent simvastatin (SIM) was encapsulated within the mesopores, followed by the electrostatic assembly of chondroitin sulfate (CS) onto the surface to yield the engineered nanozyme, CS-PEI/PB@SIM (CPPS). This platform achieves precise targeting of CD44 receptors overexpressed on macrophages and VSMCs within the plaque microenvironment. Both in vitro and in vivo experiments demonstrate that CPPS exerts potent multi-enzyme activities that functionally complement PB-mediated photothermal therapy (PTT) to quench ROS and effectively alleviate inflammatory responses. More importantly, this engineered nanozyme restores inflammation-lipid homeostasis, suppresses foam cell formation, and significantly reduces plaque burden in AS model mice. Collectively, our findings suggest that CPPS represents a promising nanotherapeutic intervention for the comprehensive management of AS.

Cancer remains a global health challenge, calling for integrated strategies that combine precise diagnosis with synergistic treatment. Although glucose oxidase (GOx)-mediated starvation therapy disrupts tumor metabolism by converting glucose into cytotoxic hydrogen peroxide (H₂O₂), its clinical translation is hindered by inefficient delivery and insufficient monotherapy efficacy. To address these issues, we developed a multifunctional nanoplatform by encapsulating GOx within hollow porous superparamagnetic Fe₃O₄ nanoparticles (Fe₃O₄-GOx NPs) to preserve its catalytic activity and enable high loading capacity. This system simultaneously enables magnetic resonance imaging (MRI), photothermal therapy, and enzyme-mediated catalytic intervention. In vitro studies demonstrated strong T₂-weighted MRI contrast for precise tumor localization, together with near-infrared laser-triggered hyperthermia that enhance the efficacy of GOx-mediated starvation therapy, elevating oxidative stress and promoting apoptosis in 4T1 cells. In 4T1 tumor-bearing mice, a single administration of Fe₃O₄-GOx NPs combined with laser irradiation elicited potent tumor suppression through the synergistic effects of intratumoral ROS generation, glucose depletion, and localized photothermal ablation, outperforming either modality alone. Histopathological assessment revealed negligible systemic toxicity and preserved organ integrity. This work presents an integrated theranostic nanoplatform that unites tumor-targeted imaging, enzyme- driven metabolism intervention, and photothermal therapy into a single system, offering a promising strategy for precision cancer management.