Colloids and Surfaces B: Biointerfaces最新文献

Albendazole (ABZ), an anthelmintic drug, has been repurposed to treat various types of cancers. However, poor solubility of ABZ, resulting in low bioavailability, limits its application. Nanosuspension is a versatile method for enhancing the dissolution of hydrophobic molecules, but a successful drying has been the biggest challenge in the field. The objective of this research is to formulate and optimize ABZ nanosuspension (NS) coated granules for rapid delivery of ABZ for the treatment of colorectal cancer. ABZ NS was prepared by dual centrifugation method using Kollidon® VA64 and sodium lauryl sulphate (SLS) as stabilizers. The processing method was optimized to obtain a stable nanosuspension with particle size < 300 nm. The optimized ABZ NS was coated on microcrystalline cellulose (MCC) to form the nano-coated granules (NCG) and filled in EUDRACAP® for colon targeted delivery. The ABZ NS and NCG achieved ∼ 60 % and ∼55 % drug release, respectively, in presence of bile salt at colonic pH. Half-maximal inhibitory concentration (IC₅₀) of ABZ NS was found to be 1.18 ± 0.081 µM and 3.59 ± 0.080 µM in two colorectal cancer cell lines: HCT 116 and HT-29, respectively. In addition, In vitro 3D tumor assay revealed that ABZ NS has superior tumor growth inhibition activity compared to the control and pure ABZ. The preparation of ABZ NCG in EUDRACAP® could be a promising approach to achieve colon targeted delivery and to repurpose ABZ for the treatment of colorectal cancer.

The global crisis of antibiotic resistance has impelled the exigency to develop more effective drug delivery systems for the treatment of bacterial infection. The development of possessing high biocompatibility and targeted delivery of antimicrobials remains a persisting challenge. For programmable release of efficient antimicrobials in infection sites to enhance antibacterial activity, herein, we fabricated diselenide-bridged mesoporous organosilica nanoparticle-supported silver nanoparticles (Ag NPs) with high drug-loading capacity for the co-delivery of tobramycin (TOB) within one drug delivery system (Ag-MON@TOB (Se)). The resultant Ag-MON@TOB (Se) exhibited favorable biocompatibility due to its high stability in the physiological condition. Notably, such Ag-MON@TOB (Se) manifested a programmable structural destabilization to trigger sequential drug release in response to the oxidative stimuli within the bacterial infection microenvironment. In contradistinction to the oxidation-stable disulfide bond moieties within the framework of the nanocarrier (Ag-MON@TOB (S)), the Ag-MON@TOB (Se) with its programmed drug release behavior augmented prominent antibacterial therapy both in vitro and in vivo. This work represents a promising strategy for programmable drug release by harnessing a responsive degradable vehicle to enhance the treatment of bacterial infection.

Clinical trials based on a single molecular target continue to fail, and the adverse effects of Aβ protein aggregation and neuroinflammation need to be solved and treatment of Alzheimer's disease. Herein, by designed a nano-sized flower mesoporous selenium transport carrier (Met@MSe@Tf) with high enzyme-like activity, metformin (Met) was loaded, and transferrin (Tf) was modified to bind to transferrin receptor to promote receptor-mediated transport across the BBB. In the AD lesion environment, with the acidic environment response dissociation, promote the release of metformin by nanoflower to achieve therapeutic effect in the brain lesion site. Metformin, a major anti-diabetic drug in diabetic metabolism, has been found to be a promising new therapeutic target in neurodegenerative diseases. Further studies showed that the metformin drug release from the designed and synthesized transport nanoparticles showed high intrinsic activity and the ability to degrade the substrate involved, especially the degradation of Aβ deposition in the cortex and hippocampus, increased the phagocytosis of microglia, thus relieving neuroinflammation simultaneously. Collectively, in vivo experiments demonstrated that Met@MSe@Tf significantly increased the number of NeuN-positive neurons in the hippocampus of AD mice, promoted neurovascular normalization in the brain, and improved cognitive dysfunction in AD transgenic AD mice. Thus, it provides a preclinical proof of concept for the construction of a highly modular accurate drug delivery platform for Alzheimer's disease.

Healing wounds presents a significant challenge due to bacterial biofilm infections and the inherent drug resistance of these biofilms. This report introduces a multifunctional nanoplatform (NPs) designed to combat wound biofilm infections using NIR-II photothermal therapy. The NPs are self-assembled from amphiphilic polymers (AP) to encapsulate photothermal polymers (PT) through classic electrostatic interactions. Importantly, these NPs are electrically neutral, which enhances their ability to penetrate biofilms effectively. Once inside the biofilm, the NPs achieve complete thermal ablation of the biofilm under NIR-II laser irradiation. Additionally, when exposed to laser and the GSH microenvironment, the NPs exhibit strong photothermal effects and self-degradation capabilities. In vitro tests confirm that the NPs have excellent antibacterial and anti-biofilm properties against methicillin-resistant Staphylococcus aureus (MRSA). In vivo studies demonstrate that the NPs can efficiently clear wound biofilm infections and promote wound healing. Notably, the NPs show superior photothermal effects under NIR-II laser irradiation compared to NIR-I lasers. In summary, the developed NPs serve as an integrated diagnostic and therapeutic nano-antimicrobial agent, offering promising applications for biofilm wound infections and wound healing.

Skull base defects are a common complication after transsphenoidal endoscopic surgery, and their commonly used autologous tissue repair has limited clinical outcomes. Tissue-engineered scaffolds prepared by advanced techniques of electrostatic spinning and three-dimensional (3D) printing was an effective way to solve this problem. In this study, soft tissue scaffolds consisting of centripetal nanofiber mats and 3D-printed hard tissue scaffolds consisting of porous structures were prepared, respectively. And the two layers were combined to obtain bilayer composite scaffolds. The physicochemical characterization proved that the nanofiber mat prepared by polylactide-polycaprolactone (PLCL) electrospinning had a uniform centripetal nanofiber structure, and the loaded bFGF growth factor could achieve a slow release for 14 days and exert its bioactivity to promote the proliferation of fibroblasts. The porous scaffolds prepared with polycaprolactone (PCL), and hydroxyapatite (HA) 3D printing have a 300 μm macroporous structure with good biocompatibility. In vivo experiments results demonstrated that the bilayer composite scaffold could promote soft tissue repair of the skull base membrane through the centripetal nanofiber structure and slow-release of bFGF factor. It also played the role of promoting the regeneration of the skull base bone tissue. In addition, the centripetal nanofiber structure also had a promotional effect on the regeneration of skull base bone tissue.

Ferroptosis, which depends on iron ions to generate reactive oxygen species (ROS), has been proved to be an effective strategy for cancer therapy. However, cells will initiate different programs, including reducing iron uptake and storing excess iron in ferritin, to lower the intracellular iron concentration. In this work, we reported a simple, one-pot method to synthesize bovine serum albumin stabilized MnFe₂O₄ nanoparticles (MnFe₂O₄@BSA NPs) for ferroptosis therapy of cancer. Artemisinin (ART) and salinomycin (Sali), which could induce the degradation of ferritin and enhance the uptake by increasing binding protein IRP2 and transferrin receptor, were loaded onto the MnFe₂O₄@BSA NPs to strengthen the killing effect. The prepared MnFe₂O₄@BSA-ART/Sali (MnFe₂O₄/ART/Sali) NPs could significantly increase the cellular iron concertation, enhancing the ROS generation in cells. After intravenous injection, the MnFe₂O₄/ART/Sali NPs showed superior anti-tumor effects, with a tumor inhibition rate of 67.65 %. Hence, the hybrid nanocomposite indicated the combined effect of MnFe₂O₄, ART, and Sali, providing a platform to enhance ferroptosis therapy of cancer.

For cancer patients with a high risk of ovarian tissue metastasis, ovarian autotransplantation is not advised due to the potential spread of malignant cells. Ex vivo purging of ovarian fragments may offer a more suitable alternative for fertility restoration. Eradicating malignant cells should be done selectively without affecting follicles or ovarian stromal cells (SCs). As a clinically licensed method, photodynamic therapy (PDT) is a minimally invasive treatment to destroy cancer cells. This study evaluates the effectiveness of nanoemulsions (NE) containing two phthalocyanine photosensitizers; aluminum (III) phthalocyanine (AlPc) and zinc (II) phthalocyanine (ZnPc) in eliminating cancer cells. Human leukemic malignant (HL-60) and ovarian stromal cells (SCs) were treated with AlPc/ZnPc loaded NEs with or without diode laser irradiation. HL-60 leukemia cells in 2D culture were eliminated by treatment with 10 nM AlPc-NE or 0.1 µM ZnPc-NE, while no toxicity was observed in SCs. In 3D culture models, although the cells showed more resistance to the NEs as a result of limited oxygen and photosensitizer penetration, the treatment remained selective for cancer cells. These approaches have the potential to eliminate malignant cells from ovarian tissue fragments.

The misuse of antibiotics has led to the growing problem of multidrug-resistant (MDR) bacteria, and there is still a lack of effective antibacterial agents that can replace antibiotics. Therefore, the design and development of multifunctional nanomaterials with long-term inhibitory effects on drug-resistant bacteria are extremely challenging. In this study, a multifunctional biomimetic self-assembly system, BSA-ZnO&Quercetin, based on bovine serum albumin (BSA), ZnO, and quercetin, was established using a simple and controllable method. The prepared self-assembly system has high stability and biocompatibility, and could fully combine the performance advantages of each component. BSA-ZnO&Quercetin showed excellent broad-spectrum antibacterial activity without inducing bacterial resistance. The related antibacterial mechanism of BSA-ZnO&Quercetin primarily involves biofilm inhibition and destruction, and inducing the production of reactive oxygen species, resulting in the death of the bacteria. The biomimetic self-assembly system BSA-ZnO&Quercetin constructed in this research is expected to replace antibiotics for antibacterial application.

Several anions present in the extracellular matrix (ECM) not only have significant physiological functions in ECM but also play an important role in regulating peptide-based self-assembly. Herein, we have employed a non-conventional approach to overcome the limitations of the positively charged Cardin-motif peptide that failed to self-assemble at physiological pH. We used a simple and elegant strategy by employing different anions such as HPO₄^2-, Cl^- and I^- to mask the overall surface charge of peptide. Interestingly, these anions were utilized to modulate the nanostructure formation and mechanical stiffness of peptide hydrogels owing to their differential interactions with water molecules according to the Hofmeister series. Interestingly, these anions induced hydrogels showed diverse cellular responses on two different cell lines, fibroblast and neuronal, indicating diverse application potential of the new scaffold. Thus, this study emphasizes the importance of anions to regulate the self-assembly of Cardin-motif peptide and this approach can be utilized in developing the ideal biomimetic model of ECM for futuristic applications.

Landfill leachate, a complex mixture of pollutants, poses a significant environmental hazard. This study reports the synthesis and characterization of superabsorbent nanocomposites (SANs) designed for enhanced performance in waste management applications. SANs were prepared using carboxymethyl cellulose (CMC) and sodium polyacrylate (SPA) as the main components, carbon dots (CDs) to improve absorption, and Satureja Khuzestanica essential oil (SEO) for antibacterial performance. The results demonstrated that the addition of CDs significantly increased the absorption capacity and liquid retention of the samples, with a water absorption capacity reaching up to 8621 %. Furthermore, the samples exhibited high mechanical strength, with tensile strength improving by over 100 % in the presence of CDs. The inclusion of SEO provided strong antibacterial activity against Escherichia coli and Staphylococcus aureus, with inhibition zones measuring up to 26 mm. These SANs, with their high absorption capacity, mechanical robustness, and antibacterial properties, show great potential for improving waste management practices, particularly in leachate absorption strategies.