Acid-Activated TAT Peptide-Modified Biomimetic Boron Nitride Nanoparticles for Enhanced Targeted Codelivery of Doxorubicin and Indocyanine Green: A Synergistic Cancer Photothermal and Chemotherapeutic Approach.

The evolution of nano-drug delivery systems addresses the limitations of conventional cancer treatments with stimulus-responsive nanomaterial-based delivery systems presenting temporal and spatial advantages. Among various nanomaterials, boron nitride nanoparticles (BNNs) demonstrate significant potential in drug delivery and cancer treatment, providing a high drug loading capacity, multifunctionality, and low toxicity. However, the challenge lies in augmenting nanomaterial accumulation exclusively within tumors while preserving healthy tissues. To address this, we introduce a novel approach involving cancer cell membrane-functionalized BNNs (CM-BIDdT) for the codelivery of doxorubicin (Dox) and indocyanine green to treat homologous tumor. The cancer cell membrane biomimetic CM-BIDdT nanoparticles possess highly efficient homologous targeting capabilities toward tumor cells. The surface modification with acylated TAT peptides (dTAT) further enhances the nanoparticle intracellular accumulation. Consequently, CM-BIDdT nanoparticles, responsive to the acidic tumor microenvironment, hydrolyze amide bonds, activate the transmembrane penetrating function, and achieve precise targeting with substantial accumulation at the tumor site. Additionally, the photothermal effect of CM-BIDdT under laser irradiation not only kills cells through thermal ablation but also destroys the membrane on the surface of the nanoparticles, facilitating Dox release. Therefore, the fabricated CM-BIDdT nanoparticles orchestrate chemo-photothermal combination therapy and effectively inhibit tumor growth with minimal adverse effects, holding promise as a new modality for synergistic cancer treatment.

Immobilizing c(RGDfc) on the surface of metal-phenolic networks by thiol-click reaction for accelerating osteointegration of implant.

The limited osteointegration often leads to the failure of implant, which can be improved by fixing bioactive molecules onto the surface, such as arginyl-glycyl-aspartic acid (RGD): a cell adhesion motif. Metal-Phenolic Networks (MPNs) have garnered increasing attention from different disciplines in recent years due to their simple and rapid process for depositing on various substrates or particles with different shapes. However, the lack of cellular binding sites on MPNs greatly blocks its application in tissue engineering. In this study, we present a facile and efficient approach for producing PC/Fe@c(RGDfc) composite coatings through the conjugation of c(RGDfc) peptides onto the surface of PC/Fe-MPNs utilizing thiol-click reaction. By combined various techniques (ellipsometry, X-ray photoelectron spectroscopy, Liquid Chromatography-Mass Spectrometry, water contact angle, scanning electronic microscopy, atomic force microscopy) the physicochemical properties (composition, coating mechanism and process, modulus and hydrophilicity) of PC/Fe@c(RGDfc) surface were characterized in detail. In addition, the PC/Fe@c(RGDfc) coating exhibits the remarkable ability to positively modulate cellular attachment, proliferation, migration and promoted bone-implant integration in vivo, maintaining the inherent features of MPNs: anti-inflammatory, anti-oxidative properties, as well as multiple substrate deposition. This work contributes to engineering MPNs-based coatings with bioactive molecules by a facile and efficient thiol-click reaction, as an innovative perspective for future development of surface modification of implant materials.

Engineering tunable dual peptide hybrid coatings promote osseointegration of implants.

Utilizing complementary bioactive peptides is a promising surface engineering strategy for bone regeneration on osteogenesis. In this study, we designed block peptides, (Lysine)6-capped RGD (K6-(linker-RGD)3) and OGP (K6-linker-(YGFGG)2), which were mildly grafted onto PC/Fe-MPNs through supramolecular interactions between K6 and PC residues on the MPNs surface to form a dual peptide coating, named PC/Fe@K6-RGD/OGP. The properties of the block peptides coating, including mechanics, hydrophilicity, chemical composition, etc., were detailly characterized by various techniques (ellipsometry, quartz crystal microbalance, X-ray photoelectron spectroscopy, water contact angle, scanning electronic microscopy and atomic force microscopy). Importantly, the RGD/OGP ratio can be well adjusted, which allowed optimizing the RGD/OGP ratio to endow significantly enhanced osteogenic activity of MC3T3-E1 cells through the Wnt/ß-catenin pathway, while also promoting cell adhesion, immune regulation, inhibiting osteoclast differentiation and oxidative stress reduction. In vivo, the optimized RGD/OGP coatings promoted bone regeneration and osseointegration around implants in rats with bone defects. In conclusion, rationally designed PC/Fe@K6-RGD/OGP coating integrated RGD and OGP bioactivities, providing a convenient approach to enhance bioinert implant surfaces for bone regeneration.

Biomimetic Boron Nitride Nanoparticles for Targeted Drug Delivery and Enhanced Antitumor Activity.

Boron nitride nanomaterials are being increasingly recognized as vehicles for cancer drug delivery that increase drug loading and control drug release because of their excellent physicochemical properties and biocompatibility. However, these nanoparticles are often cleared rapidly by the immune system and have poor tumor targeting effects. As a result, biomimetic nanotechnology has emerged to address these challenges in recent times. Cell-derived biomimetic carriers have the characteristics of good biocompatibility, long circulation time, and strong targeting ability. Here, we report a biomimetic nanoplatform (CM@BN/DOX) prepared by encapsulating boron nitride nanoparticles (BN) and doxorubicin (DOX) together using cancer cell membrane (CCM) for targeted drug delivery and tumor therapy. The CM@BN/DOX nanoparticles (NPs) were able to target cancer cells of the same type on its own initiative through homologous targeting of cancer cell membranes. This led to a remarkable increase in cellular uptake. In vitro simulation of an acidic tumor microenvironment could effectively promote drug release from CM@BN/DOX. Furthermore, the CM@BN/DOX complex exhibited an excellent inhibitory effect against homotypic cancer cells. These findings suggest that CM@BN/DOX are promising in targeted drug delivery and potentially personalized therapy against their homologous tumor.

A novel method of calcium dissolution-crystallization-polymerization for stabilization/solidification of MSWI fly ash.

Municipal solid waste incineration fly ash (MSWI FA) stabilization/solidification using calcium carbonate (CaCO3) oligomer is an efficient, low-carbon disposal method. The insoluble Ca in FA was converted to free-Ca, utilizing for CaCO3 oligomer preparation, which was crystallized and polymerized by thermal induction to develop continuous cross-link or bulk structures for stabilization/solidification of potentially toxic elements (PTEs, e.g., lead (Pb) and zinc (Zn)). Experimental results showed that the weakly alkaline acid-leaching suspension provided an excellent condition for the generation of CaCO3 oligomers, with Pb and Zn immobilization reaching over 99.4%. With the acid strengthening of the suspension, H+ took the lead in protonating with TEA and limiting the capping action of TEA, which was harmful to the synthesis of CaCO3 oligomers. Ethanol with a low dielectric constant was considered an ideal solvent for oligomer production, and triethylamine (TEA) as a capping agent established hydrogen bonds (N⋯H) with protonated CaCO3. H2O molecules competed with the protonated CaCO3 molecules for TEA with ethanol concentration decreasing, resulting in erratic precipitation of CaCO3 molecules and significantly elevated leaching risk of Pb and Zn. The sequential extraction procedure, pH-dependent leaching, and geochemical analysis results revealed that the dissolution/precipitation of Ca, Pb, and Zn in treated FA was mostly controlled by the carbonate mineral phases. Moreover, the low boiling points of ethanol and TEA can be recovered for recycling. The gel-like, flexible combination of CaCO3 oligomers and FA particles formed by FA offers great resource utilization potential via a controlled crystallization polymerization process.

Deletion of Arrb2 Down-regulates Autophagy in the Mouse Hippocampus via Akt-mTOR Pathway Activation.

The cytoplasmic multifunctional adaptor protein ß-arrestin 2 (Arrb2) is involved in the occurrence of various nervous system diseases, such as Alzheimer's disease and Parkinson's disease. Previous laboratory studies have shown that the expression and function of the Arrb2 gene was increased in valproic acid-induced autistic mice models. However, few reports have examined the possible role of Arrb2 in the pathogenesis of autism spectrum disorder. Therefore, Arrb2-deficient (Arrb2-/-) mice were further studied to uncover the physiological function of Arrb2 in the nervous system. In this study, we found that Arrb2-/- mice had normal behavioral characteristics compared with wild-type mice. The autophagy marker protein LC3B was decreased in the hippocampus of Arrb2-/- mice compared to wild-type mice. Western blot analysis revealed that deletion of Arrb2 caused hyperactivation of Akt-mTOR signaling in the hippocampus. In addition, abnormal mitochondrial dysfunction was observed in Arrb2-/- hippocampal neurons, which was characterized by a reduction in mitochondrial membrane potential and adenosine triphosphate production and an increase in reactive oxygen species levels. Therefore, this study elucidates the interaction between Arrb2 and the Akt-mTOR signaling pathway and provides insights into the role of Arrb2 in hippocampal neuron autophagy.

Macrophage migration inhibitory factor protects bone marrow mesenchymal stem cells from hypoxia/ischemia-induced apoptosis by regulating lncRNA MEG3.

OBJECTIVES: This research was performed to explore the effect of macrophage migration inhibitory factor (MIF) on the apoptosis of bone marrow mesenchymal stem cells (BMSCs) in ischemia and hypoxia environments. METHODS: The cell viability of BMSCs incubated under hypoxia/ischemia (H/I) conditions with or without pretreatment with MIF or triglycidyl isocyanurate (TGIC) was detected using cell counting kit-8 (CCK-8) analysis. Plasmids containing long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) or ß-catenin small interfering RNA (siRNA) were used to overexpress or downregulate the corresponding gene, and the p53 signaling pathway was activated by pretreatment with TGIC. The influences of MIF, overexpression of lncRNA MEG3, activation of the p53 signaling pathway, and silencing of ß-catenin on H/I-induced apoptosis of BMSCs were revealed by western blotting, flow cytometry, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining. RESULTS: From the results of CCK-8 assay, western blotting, and flow cytometry, pretreatment with MIF significantly decreased the H/I-induced apoptosis of BMSCs. This effect was inhibited when lncRNA MEG3 was overexpressed by plasmids containing MEG3. The p53 signaling pathway was activated by TGIC, and ß-catenin was silenced by siRNA. From western blot results, the expression levels of ß-catenin in the nucleus and phosphorylated p53 (p-p53) were downregulated and upregulated, respectively, when the lncRNA MEG3 was overexpressed. Through flow cytometry, MIF was also shown to significantly alleviate the increased reactive oxygen species (ROS) level of BMSCs caused by H/I. CONCLUSIONS: In summary, we conclude that MIF protected BMSCs from H/I-induced apoptosis by downregulating the lncRNA MEG3/p53 signaling pathway, activating the Wnt/ß-catenin signaling pathway, and decreasing ROS levels.

Sargassum fusiforme fucoidan ameliorates diet-induced obesity through enhancing thermogenesis of adipose tissues and modulating gut microbiota.

Obesity has become a global epidemic. Sargassum fusiforme fucoidan (Fuc) is a group of water-soluble heteropolysaccharides that exhibits a wide range of medicinal functions. It consists of l-fucose and sulfate groups, with l-fucose as the main monosaccharide. This study investigated the therapeutic effects of Fuc on diet-induced obesity (DIO) in C57BL/6J female mice. Fuc significantly alleviated obesity in mice induced by high-fat high-fructose (HFHF) feeding, inhibiting body weight gain, reducing fat accumulation, and improving hepatic steatosis. In addition, Fuc significantly improved glucose tolerance and insulin sensitivity by enhancing the phosphorylation level of AKT (at Ser473) in the adipose tissues. Mechanistically, although Fuc did not decrease the energy intake in DIO mice, it significantly increased the energy expenditure by up-regulating the expression of uncoupling protein 1 (UCP1) in the adipose tissues. Notably, Fuc also improved the obesity-driven dysbiosis of gut microbiota and decreased the relative abundance of the obesity-related intestinal bacteria. However, Fuc was unable to alleviate DIO-induced metabolic disorders in pseudo-sterile mice. Our findings suggested that Fuc might remodel gut microbiota and exert its weight loss and hypolipidemic effects by increasing the energy expenditure, thus providing a novel perspective for treating obesity and related complications.

Different extraction methods bring about distinct physicochemical properties and antioxidant activities of Sargassum fusiforme fucoidans.

Fucoidan is a complex sulfated polysaccharide and an active component found in the cell wall of brown seaweeds. In the present study, fucoidans were obtained from Sargassum fusiforme using different extraction methods, including hot water (prepared fucoidan was named as WSFF), dilute hydrochloric acid (ASFF), and calcium chloride solution (CSFF). The assessments were performed on S. fusiforme fucoidans based on their chemical composition, molecular conformations, and in vitro antioxidant activities. ASFF showed the maximum extraction yield (11.24%), whereas CSFF exhibited the minimum yield (3.94%). The monosaccharide composition of WSFF, ASFF, and CSFF was similar, but the molar ratio of monosaccharide was quite different. Moreover, their molecular weight, Fourier transform infrared (FT-IR) spectrum, surface morphology, uronic acid content and degree of sulfation were distinct. The Congo red test and Circular dichroism spectroscopy analysis displayed some differences in solution conformation of these samples. Furthermore, WSFF, ASFF, and CSFF showed distinct in vitro antioxidant activities evaluated by DPPH and hydroxyl radical scavenging assays. The present study provides scientific evidence on the influences of extraction methods on the physicochemical characteristics, conformation behaviors and antioxidant activities of S. fusiforme fucoidans.