Journal of materials chemistry. B最新文献

Objective. The purpose of this study is to develop, optimize, and evaluate the in vivo effectiveness of orally administered silibinin-loaded nanostructured lipid carriers (SB-NLCs) in amyloid β-induced Alzheimer's disease in Wistar rats. Methods. The emulsification-solvent evaporation method was used for preparing the NLCs, using stearic acid, triacetin, and Cremophor® RH40. The statistical optimization of SB-NLCs was done using the Box-Behnken design (BBD). Then, the following parameters were evaluated: zeta potential, average size, in vitro drug release, and drug entrapment efficiency. Physicochemical properties of the optimized SB-NLCs were determined by FTIR, DSC, and P-XRD. The behavioral (OFT, NOR, MWM), histological (H&E, Congo Red), and biochemical (TAC, MDA, GSH) tests were conducted on 48 male Wistar rats. Results. The findings showed that the mean particle size, zeta potential and entrapment efficiency of optimized SB-NLCs were 194.71 ± 14.06 nm, -12.46 ± 0.25 mV, and 72.13% ± 1.41, respectively. XRD and DSC studies confirmed a reduction in the crystallinity of SB which occurred due to its embedment in the nanostructured lipid. The FTIR results indicated the lack of existence of any chemical interaction between the carrier components and the drug. Drug release in the external environment was slow and steady. Drug-containing nanoparticles showed good stability during three months of storage at 4 °C. The behavioral test of OFT showed no significant change between groups. The group treated with SB-NLCs showed a markedly higher discrimination rate compared to the Aβ group (p < 0.001). The time of the SB-NLC treated group in the target area was considerably more than the time of the SB and Aβ groups, respectively (p < 0.01, p < 0.001), in the MWM test. Histological and biochemical analysis revealed better results in the SB-NLC group as against the SB group. Conclusion. SB-NLCs can be considered as a promising formulation for the proper treatment of Alzheimer's disease in the oral drug delivery system.

Collective behavior has become a recent topic of investigation in systems chemistry. In pursuing this phenomenon, we present polymersome stomatocytes loaded with the enzyme urease, which show basic stigmergy-based communication and are capable of signal production, reception, and response by clustering with surface complementary binding partners. The collective behavior is transient and based on the widely known pH-sensitive non-covalent interactions between nitrilotriacetic acid (NTA) and histidine (His) moieties attached to the surface of urease-loaded and empty stomacytes, respectively. Upon the addition of the substrate urea, the urease stomatocytes are able to increase the environmental pH, allowing the NTA units to interact with the surface histidines on the complementary species, triggering the formation of transient clusters. The stomatocytes display a maximum clustering interaction at a pH between 6.3 and 7.3, and interparticle repulsive behavior outside this range. This leads to oscillating behavior, as the aggregates disassemble when the pH increases due to high local urease activity. After bulk pH conditions are restored, clustering can take place again. Within the detectable region of dynamic light scattering, individual stomatocytes can aggregate to agglomerates with 10 times their volume. Understanding and designing population behavior of active colloids can facilitate the execution of cooperative tasks, which are not feasible for individual colloids.

Musculoskeletal disorders are on the rise, and despite advances in alternative materials, treatment for orthopedic conditions still heavily relies on biometal-based implants and scaffolds due to their strength, durability, and biocompatibility in load-bearing applications. Bare metallic implants have been under scrutiny since their introduction, primarily due to their bioinert nature, which results in poor cell-material interaction. This challenge is further intensified by mechanical mismatches that accelerate failure, tribocorrosion-induced material degradation, and bacterial colonization, all contributing to long-term implant failure and posing a significant burden on patient populations. Recent efforts to improve orthopedic medical devices focus on surface engineering strategies that enhance the interaction between cells and materials, creating a biomimetic microenvironment and extending the service life of these implants. This review compiles various physical, chemical, and biological surface engineering approaches currently under research, providing insights into their potential and the challenges associated with their adoption from bench to bedside. Significant emphasis is placed on exploring the future of bioactive coatings, particularly the development of smart coatings like self-healing and drug-eluting coatings, the immunomodulatory effects of functional coatings and biomimetic surfaces to tackle secondary infections, representing the forefront of biomedical surface engineering. The article provides the reader with an overview of the engineering approaches to surface modification of metallic implants, covering both clinical and research perspectives and discussing limitations and future scope.

Cascading enzymatic therapy is a promising approach in cancer treatment. However, its effectiveness is often hindered by enzyme inactivation, limited exposure of active sites, cancer cell self-protection mechanisms such as autophagy, and non-specific toxicity, which can lead to treatment failure. To address these challenges, we used a low-temperature aqueous-phase synthesis method to create semi-crystalline, water-dispersible fluorescent COF nanospheres. These nanospheres can stably load glucose oxidase (GOx) and ultrafine Fe₂O₃ nanozymes, allowing for convenient coating with tumor cell membranes to form a uniform tumor-targeted cascading enzymatic nanosystem (CFGM). This system promotes a cycle of tumor glucose depletion, reactive oxygen species (ROS) generation, and oxygen production, facilitating tumor-targeted starvation therapy (ST) and chemodynamic therapy (CDT). Notably, the semi-crystalline COF carrier within this system can degrade slowly under mildly acidic conditions, forming large aggregates that damage lysosomes and disrupt lysosomal autophagy, thereby eliminating the autophagy protection of cancer cells activated by the combined ST. This synergistic approach enhances the catalytic inhibition of tumors. Our research thus provides an alternative COF-based platform and strategy for effective cancer treatment.

Sensitive imaging of microRNAs (miRNAs) in tumor cells holds great significance in the domains of pathology, drug development, and personalized diagnosis and treatment. DNA nanostructures possess excellent biostability and programmability and are suitable as carriers for intracellular imaging probes. With its highly controllable motion mechanism and remarkable target recognition specificity, the DNA walker is an ideal tool for living cell imaging. Here, we report a DNA nanowire based-DNAzyme Walker (D-Walker), which loads the DNAzyme based-molecular beacon (D-MB) onto DNA nanowires (NWs) functionalized with aptamers. The experimental results demonstrated that the intracellular target miRNA can specifically activate the pre-locked DNAzyme through a strand displacement reaction, thereby triggering the cleavage of its substrate molecular beacon (MB) and subsequent fluorescence emission. NWs decorated with aptamers can effectively prevent the degradation of the D-Walker by nuclease, and can enter target cells without any transfection reagents, which enhances the stability and reliability of cell imaging. Furthermore, the D-Walker exhibited a remarkable sensitivity with a limit of detection (LOD) of 61 pM and was capable of distinguishing miRNA-21 from other closely related family members. This study provides a novel strategy for intracellular miRNA imaging, offering a promising tool for cancer diagnosis and treatment.

TiO₂ nanotubes (NTs) obtained via electrochemical anodization (EA) on conventionally machined titanium surfaces are reported to be promising for achieving mucointegration in dental implant therapy. Dental abutments, manufactured by selective laser melting (SLM), combined with thermal post-treatment, present a promising alternative to conventionally machined titanium. Based on an original protocol, this study aims to investigate how the characteristic microstructure of the α + β phases in post-heated SLM Ti6Al4V can influence the growth of NTs and the resulting physical and chemical surface properties. Ti6Al4V-SLM discs were fabricated, heat post-treated and mechanically polished. The samples were then subjected to EA under different voltage conditions (10, 20 and 30 V). The specimens' surfaces were characterized at the same location, before NTs formation by electron backscatter diffraction (EBSD), and after by scanning electron microscopy (SEM). Then, roughness and wettability were studied to determine how EA affects surface properties compared to conventionally machined and polished titanium surfaces without NTs (reference). Surface reactivity was evaluated through chemical analysis and collagen binding capacities. The self-organized TiO₂ layer was developed on the α phase only and the β phase was preferentially dissolved. The characteristic dimensions of the nanotubes (diameter, length and wall thickness), measured by SEM image analysis, increased proportionally with the rise in voltage but were not affected by the crystallographic orientation of the underlying α grain. Micro-roughness was the same for nanotubular and reference surfaces. Wettability was improved, as was surface reactivity towards collagen, which may contribute to improved bioactivity of titanium surfaces in dentistry.

Recently, the emerging chemotherapy (CDT) has provided a new biocompatibility pathway for cancer therapy. Among them, Cu-based nanocatalysts with good biocompatibility and Fenton-like catalytic efficiency are considered to be a promising approach for enhancing CDT and CDT-involved multimodal synergies to improve the effectiveness of catalytic cancer therapy. Meanwhile, the emerging in situ therapy strategy promoted by Cu-based nanocatalysts has proven to exhibit attractive clinical application potential in replacing traditional chemotherapy and radiotherapy for cancer therapy with significant toxic side effects. In this work, the recent progress of various Cu-based nanocatalysts in cancer therapy was reviewed, especially the remarkable achievements in the catalytic treatment of cancer in the tumor microenvironment using CDT and CDT-involved multimodal synergies. In addition, the development expectations and challenges of Cu-based nanocatalysts in the field of cancer therapy were briefly summarized and discussed. We expect that this review will contribute to the development of Cu-based nanocatalysts for cancer therapy.

Methaemoglobin (metHb) possesses inherent characteristics that facilitate reversible binding to hydrogen sulphide. Exogenous hydrogen sulphide supplementation imparts beneficial bioactive effects, including antioxidant and anti-inflammatory; hence, we hypothesized that the metHb-hydrogen sulphide complex could act as a hydrogen sulphide donor for medication. In this study, we prepared a hydrosulphide-metHb-albumin (H₂S-metHb-albumin) cluster and examined its applicability as a hydrogen sulphide donor in the mice model of hepatic ischemia-reperfusion injury. Structural analysis revealed that the H₂S-metHb-albumin cluster exhibited a nanostructure wherein one metHb was wrapped by an average of three albumins, and hydrogen sulphide was bound to the haem. Additionally, the H₂S-metHb-albumin cluster exhibited low-pH responsiveness, leading to sustained release of hydrogen sulphide. Owing to these structural and pharmaceutical characteristics, the severity of hepatic ischemia-reperfusion injury was alleviated via antioxidant and anti-inflammatory effects of the H₂S-metHb-albumin cluster treatment. The protective effects were more potent in the H₂S-metHb-albumin cluster compared to that in a conventional hydrogen sulphide donor (sodium hydrogen sulphide). No abnormal signs of toxic and biological responses were observed after the H₂S-metHb-albumin cluster administration, confirming high biological compatibility. These results successfully establish the proof of concept that the H₂S-metHb-albumin cluster is a promising hydrogen sulphide donor. To the best of our knowledge, this is the first report demonstrating the remarkable potential of metHb as a biomaterial for hydrogen sulphide donors.

A striking issue is the scarcity of imaging probes for the early diagnosis of Alzheimer's disease. For the development of Aβ biomarkers, a mitochondria targeting, de novo designed, aggregation-induced emission (AIE) probe Cou-AIE-TPP⁺ is constructed by engineering the aromatic coumarin framework into the bridge of electron donor-acceptor-donor tethered with a lipophilic cationic triphenylphosphonium (TPP⁺) group. The synthesized Cou-AIE-TPP⁺ probe exhibits biocompatibility, noncytotoxicity, and a huge Stokes shift (124 nm in PBS). Cou-AIE-TPP⁺ has respectable fluorescence augmentation inside the aggregated Aβ40 in comparison with monomeric Aβ40 with a high binding affinity (K_d = 83 nM) to Aβ40 aggregates, is capable of detecting the kinetics of amyloid aggregation, and is superior to the gold standard probe thioflavin T. Fluorescence lifetime and brightness are also augmented when the probe Cou-AIE-TPP⁺ binds with Aβ aggregates in PBS. Cou-AIE-TPP⁺ (λ_em 604 nm) selectively targets and images neuronal cell mitochondria, is useful to monitor mitochondrial morphology alteration and damage during Aβ40-induced neurotoxicity, recognizes neurotoxic Aβ fibrils, and is highly colocalized with thioflavin T, showing a decent Pearson correlation coefficient of 0.91 in the human neuroblastoma SH-SY5Y cell line. These findings indicate that the mitochondria targeting, de novo designed, functional AIE-based solvatofluorochromic Cou-AIE-TPP⁺ probe is a promising switch on biomarkers for fluorescence imaging of Aβ aggregates and to monitor mitochondrial morphology change and dysfunction during Aβ-induced neurotoxicity, which may offer imperative direction for the advancement of compelling AIE biomarkers for targeted early stage Aβ diagnosis in the future.

The abnormal pH in cell membranes can lead to disorder in membrane structure and permeability, and is also an important signal of cell cancer. The acidification of the cell membrane can lead to the disorder of cell lipid metabolism and lead to non-alcoholic fatty liver disease (NAFLD). However, fluorescent probes to detect the cell membrane pH have rarely been reported, let alone used to study NAFLD. For this, we developed a fluorescent probe (Mem-pH) that can firmly anchor the cell membrane based on lipophilic action and electrostatic action forces, and successfully detect membrane pH by fluorescence intensity. More importantly, the probe Mem-pH can quantify the pH of different kinds of cell membranes, further demonstrating that the pH of cancer cell membranes is lower than that of normal cell membranes. Furthermore, Mem-pH successfully differentiates and detects different degrees of NAFLD tissues, offering hope for timely diagnosis of NAFLD.