Colloids and Surfaces B: Biointerfaces最新文献

Exogenous microRNA-144 (miR-144) is considered as a potential biological drug for gastric cancer because of its biological activity to inhibit the epithelial-mesenchymal transition (EMT). However, the specific molecular mechanisms have not been fully revealed. In addition, their vulnerability to degradation by RNA enzymes in the blood limits their bioavailability. In this paper, a polyamidoamine (PAMAM)-wrapped miR-144 (PAMAM/miR-144) is prepared as a nanocarrier system to protect miR-144 from nuclease degradation. The PAMAM/miR-144 nanocarrier system achieves the optimal antitumor activity against gastric cancer migration and reduce mTOR protein expression by transferring miR-144 into human gastric cancer HGC-27 cells. At the same time, the PAMAM/miR-144 nanocarrier system significantly decreases the EMT via targeting mTOR signal pathway in HGC-27 cells and noticeably inhibited the growth of subcutaneous gastric cancer xenografts in nude mice. PAMAM/miR-144 nanocarrier system has effectively improved the bioavailability of miR-144, thus providing a promising combination modality for anticancer therapy.

Natural compounds have shown promising application prospects in preventing or treating various diseases, including osteoporosis on account of their abundant sources, low price, multi-targeting and multiple biological effects. As a bioactive natural product, quercetin (Que) has previously demonstrated to ameliorate osteoporosis (OP), however, its poor bioavailability resulting from low water solubility, poor stability and lack of bone-targeting largely restricted its efficacy and clinical applications. Inspired by the bone-targeting capability of phosphate compounds, we reported a one-step procedure for synthesis of phosphorylated Que (p-Que) by direct phosphorylating phenol groups of Que for the first time. The phosphate groups on p-Que could not only improve the water dispersibility of Que, but also endow p-Que desirable bioavailability and bone-targeting feature. The results from biological assays suggested that p-Que could inhibit osteoclastogenesis and bone resorption and alleviate trabeculae loss in osteoporotic mice. In conclusion, this work demonstrated that phosphorylation strategy can effectively solve low water solubility, lack of bone-targeting capability and poor bioavailability of natural compounds, providing a novel and efficient approach for development of OP nanomedicines.

The rampant use of commercial antibiotics not only increases drug resistance but also causes a significant threat to human health. This study assessed the wound healing efficacy of hydrogels crafted from carboxymethyl chitosan (Cmc), polyglutamic acid (γ-PGA), tannic acid (TA), and carbazole (Car), with the aim of expediting the wound healing process. Hydrogels were formulated using Cmc/γ-PGA, Cmc/γ-PGA/TA, and Cmc/γ-PGA/TA/Car, followed by a thorough evaluation of their physicochemical attributes. Additionally, assessments encompassed cytotoxicity, antibacterial efficacy, wound contraction rates, histopathological parameters, immunofluorescent staining of CD31, CD86, and COL1A, along with the determination of serum concentrations of IL-1β, IL-6, and IL-10. The physicochemical analyses validated the successful synthesis of the hydrogels, which exhibited both safety and potent antibacterial properties. Topical application of Cmc/γ-PGA/TA/Car hydrogels notably accelerated wound contraction, as evidenced by heightened expression of CD31 and COL1A, alongside reduced serum concentrations of IL-1β and IL-6. In essence, the Cmc/γ-PGA/TA/Car hydrogel demonstrated a dual effect of mitigating inflammation and modulating the proliferative phase, that shows their abilities for application in the wound healing process.

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.