Cerium oxide nanozymes (CeO2 NZs) exhibit enzyme mimetic activities and great promise for biomedical applications by mediating the dynamic cycling between Ce3+ and Ce4+. However, traditional preparation methods are often expensive and detrimental to the environment. Meanwhile, the problems of easy agglomeration, poor targeting and weak biocompatibility need to be solved. The available literatures have mainly reviewed CeO2 NZs in terms of its material properties, mechanisms and potential clinical applications. The literatures on the limitations of CeO2 NZs and the corresponding improvement methods are fragmented. Consequently, the limitations of CeO2 NZs and the strategies involving green preparation technology and modification mainly summarized, while the biosafety of the modification strategies are compared. Meanwhile, representative studies of potential clinical applications of CeO2 NZs over the past three years are outlined, along with a summary of their clinical translational prospects and challenges. Finally, the challenges of CeO2 NZs promotion technology are discussed.
Exploiting natural and bioactive stabilizers to fabricate green emulsions has attracted increasing attention. In this work, lactoferrin (LF) was combined with chlorogenic acid (CGA) to construct the LF-CGA complex to prepare a eugenol (EG) Pickering emulsion (ELC/PE). The surface activity and binding mechanism of LF-CGA were explored. Additionally, the antioxidant, antibacterial, and anti-inflammatory capacities of ELC/PE were compared. The contact angle of LF-CGA approached 90° (81.9°), indicating enhanced stability at the oil-water interface. The interaction between LF and CGA was primarily driven by static quenching and hydrogen bonding. The ELC/PE consisted of 1.5 wt% LF-CGA, with distilled water and EG as the aqueous and oil phases (15:1 v/v, aqueous/oil). The DPPH-, O2 -, and ABTS+ scavenging rates of ELC/PE were 86.3%, 75.3%, and 83.4%, respectively. The ELC/PE displayed superior antibacterial ability, along with inhibition rates of 99.0% and 99.5% against Candida albicans and Staphylococcus aureus, respectively. Additionally, the ELC/PE exhibited the most significant suppression of ear swelling (81.8%), confirming its anti-inflammatory ability. These values were the highest among all experimental groups. The LF-CGA complex acts as an emulsifier to enhance EG bioactivities. This novel complex holds great potential for expanding the practical applications of poorly soluble bioactive compounds.
The pathogenesis of depression is closely associated with neuronal mitophagy dysfunction and dysregulated energy metabolism. The acidic intracellular microenvironment of depressed neurons is increasingly recognized as a pivotal driver of depressive-like behaviors. Nevertheless, therapeutic strategies for this pathological feature remain largely underexplored. Meanwhile, the nasal mucosal barrier constitutes a major bottleneck for nose-to-brain drug delivery in depression treatment. Constructing carriers with superior deformability can enhance mucosal penetration and the efficiency of intracerebral delivery. Herein, an exosome (EXO)-based nanoengineered platform via conjugation of carnosine (CAR) and rabies virus glycoprotein 29 (RVG29) peptide loaded with miR-532-5p (RVG/CAR–EXOm–miR) was designed. Specifically, the elevated cholesterol content of 130% in RVG/CAR–EXOm–miR markedly reinforced the deformability of engineered exosomes and the nasal mucosal penetration, thereby improving brain delivery efficiency. Subsequently, the entire system migrated to brain neurons due to the distinct neuronal targeting capability of RVG29. Upon internalization into neurons, CAR exerted a pH-regulating function to buffer the intracellular acidic microenvironment, rescuing the impairment of synaptic plasticity and offering supportive therapeutic effects against depression. Meanwhile, miR-532-5p restored mitochondrial function. These findings demonstrate that RVG/CAR–EXOm holds great potential as an efficient nose-to-brain drug delivery system for depression therapy.
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Exosome-based therapies stand at the forefront of precision medicine, offering tailored solutions for disease-specific drug delivery and personalized treatment strategies. Addressing challenges such as the non-specific targeting of exosomes in brain diseases is crucial for optimizing therapeutic efficacy. Chemical modification of exosomes enables specific targeting of brain diseases via precise chemical reactions to conjugate brain disease-targeting ligands, functional molecules, or responsive moieties. The modification efficiency and outcomes are inherently contingent upon varying chemical reaction conditions, while the modification process itself exerts profound influences on the stability, biological activity, and functional expression of exosomes. Advanced chemical modification strategies have been demonstrated to effectively cross the blood-brain barrier (BBB), enabling spatiotemporally precise targeting of intracerebral lesion sites while maintaining their optimal biological activity and structural stability. By integrating the latest research achievements, this study reveals the unique advantages and mechanistic pathways of chemical modification in constructing highly specific targeted delivery systems for brain diseases, providing a precisely controllable novel approach for the precision therapy of brain diseases. Despite existing challenges, these advancements in chemically modified exosome research hold promise for ushering in safer, highly precise, and personalized therapies, thereby propelling the further advancement of exosomes in the therapeutic landscape of brain diseases.
The construction of organic-inorganic semiconductor heterojunctions is an important way to improve the photocatalytic performance of semiconductors and inhibit the recombination of photogenerated charge carriers. In this paper, a novel Sb₂S₃-3,4,9,10-perylene tetracarboxylic acid (Sb2S3-PTCA) heterojunction was prepared by hydrothermal method. Compared with Sb2S3 and PTCA, Sb2S3-PTCA composite catalyst had better photocatalytic reduction ability for Cr(VI) in aqueous solution under visible light conditions. The optimized Sb2S3-1.0 wt.% PTCA heterostructures exhibited significantly enhanced photocatalytic activity compared to pure Sb₂S₃ and PTAC, achieving a complete Cr(VI) reduction rate of 100 % in just 50 min. This will lead to cleaner effluent water being discharged into the environment, thereby reducing pollution and protecting aquatic ecosystems. The enhanced photocatalytic efficacy exhibited by the Sb2S3-PTCA heterostructure stems from the creation of a type II heterojunction, which facilitates a more proficient dissociation and transportation of the electron-hole pairs, thus contributing to its superior performance.
Solar-driven photocatalysis is a promising green technology for wastewater treatment. Molybdenum disulfide (MoS2) is a highly efficient visible-light photocatalyst. However, due to the rapid recombination of photoinduced electron-hole (e--h+) pairs, its photocatalytic activity is severely limited, thereby hindering its practical application. To solve this problem, a novel MoS2-3,4,9,10-perylene tetracarboxylic acid (MoS2-PTCDG) heterojunction was synthesized via a hydrothermal method. In this composite, PTCDG nanosheets are embedded in the inter-layer spaces of three-dimensional flower-like MoS2 nanospheres, forming an organic-inorganic heterostructure. This design not only improves the separation efficiency of photogenerated e--h+ pairs, but also the hydrophilic terminal carboxyl groups on PTCDG can serve as adsorption sites for Cr(VI) pollutants. The MoS2-PTCDG composite demonstrates exceptional photocatalytic activity and stability in degrading Cr(VI) under simulated sunlight, achieving a reaction rate constant 2.5 times higher than that of pure MoS2. This study highlights the potential of rationally designed organic-inorganic heterostructures to overcome the limitations of traditional MoS2-based photocatalysts, thus offering new insights into the development of high-performance photocatalytic materials for environmental remediation.
Glioblastoma (GBM) poses a formidable challenge because of its high morbidity and mortality. The therapeutic efficacy of GBM is significantly hampered by the intricate blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). Nanomaterial-based brain-targeted delivery systems have shown great potential for effectively delivering therapeutic agents for GBM treatment by overcoming the limitations of conventional drugs, such as poor BBB penetration, a short half-life, and low bioavailability. This review focuses on an in-depth analysis of the interplay between the BBB/BBTB and drug transport kinetics while analyzing innovative nanoparticle-mediated strategies for enhanced GBM treatment. Moreover, the delivery strategies of nanoparticle-based brain-targeted systems are emphasized, with particular attention given to biomimetic nanoparticles (BMNPs), whose unique advantages. The current challenges, translational potential, and future research directions in this rapidly evolving field are comprehensively discussed, highlighting advances in nanomaterial applications. This review aims to stimulate further research into GBM delivery systems, offering promising avenues for maximizing the therapeutic effects of gene drugs or chemotherapeutic agents in practical applications.
Iron deficiency anemia (IDA) is one of the most common and widespread forms of anemia, particularly affecting women during pregnancy and postpartum period. Traditional iron supplements primarily consist of inorganic iron, which is often associated with gastrointestinal side effects. In contrast, natural polysaccharide-based iron supplements are gaining popularity owing to their superior absorption, higher bioavailability, and improved biosafety profiles. Conventional methods for synthesizing polysaccharide‑iron complexes typically use sodium hydroxide (NaOH) to regulate the pH of the reaction system. However, NaOH was prone to reacting with carbon dioxide (CO2) in the air, leading to pH instability and, consequently, fluctuations in the iron content of the final product. Therefore, enhancing the iron content remains a significant challenge. Sodium bicarbonate (NaHCO3), being alkaline and better stability compared to NaOH, presents a promising alternative. Consequently, we explored the synthesis of a novel polysaccharide‑iron complex using NaHCO3 as a pH adjusting agent in this study. To address this issue of low iron content, we synthesized a cost-effective and safe Bletilla Striata polysaccharide (BSP) Fe (III) complex under alkaline conditions using an optimized fluidization additive method, with NaHCO3 as the pH regulator. The BSP-Fe (III) complex was thoroughly characterized via FT-IR, 1H NMR, XRD, SEM, DSC and TGA. The absorption properties of BSP-Fe (III) in the small intestine were investigated in vitro, along with its effects on IDA mice in vivo. Under optimized conditions-including 2 M FeCl3, 10 % NaHCO3, a BSP-to‑sodium citrate mass ratio of 1.3:1, a pH of 9.2, a reaction temperature of 81 °C, and a reaction time of 1.3 h-the BSP-Fe (III) achieved an iron content of 21.12 %, as determined by the Box-Behnken design plus response surface methodology (RSM). The complex was efficiently absorbed in duodenum and jejunum and demonstrated a significant ability to replenish blood in IDA mice. These findings highlighted that NaHCO3 can effectively replace NaOH as a pH adjuster, successfully enhancing the iron content of BSP-Fe (III) complex from 14.63 % to 21.12 %. This study provides insights that may guide future researches aimed at improving the iron content of polysaccharide-Fe (III) complexes. Furthermore, our BSP-Fe (III) complex exhibited great potential as a safe and non-toxic novel iron supplement, providing a pharmacodynamic foundation for the development of polysaccharide‑iron dosage forms.
Skin aging has become a major urgent problem to be solved. Evidence reveals that oxidation and glycosylation are two dominant inducements of aging. Resveratrol (RES) with outstanding anti-oxidant effect and carnosine (CAR) with superb anti-glycation property were selected as two model drugs to evaluate the feasibility of their synergistic anti-aging effect. RES and CAR at the most desired mass ratio, supplying the most superior synergistic anti-aging effects were further encapsulated in liposomes (LP), which were separately coated with chitosan (CS) and catechol chitosan (Cat-CS) to increase the transdermal penetration. Their anti-aging efficacy was explored in human skin fibroblast (HSF) and human immortalized keratinocytes (HaCaT) cells, as well as the back skin of guinea pigs. Herein, RES and CAR at the mass ratio of 2:1 exhibited the most ideal synergistic anti-aging effect. The constructed liposomes have been shown to possess excellent fundamental properties and sustained-release properties. The aging-related indicator levels in the two cells and guinea pigs were obviously improved for the RES + CAR@Cat-CS-LP group. Additionally, skin appearance, tissue morphology, and collagen content were visibly improved, indicating its perfect anti-aging effect. In conclusion, RES + CAR@Cat-CS-LP is expected to be exploited as a potential anti-aging drug delivery system.
The considerable challenge of wound healing remains. In this study, we fabricated a novel multifunctional core-shell nanofibrous scaffold named EGF@BSP-CeO2/PLGA (EBCP), which is composed of Bletilla striata polysaccharide (BSP), Ceria nanozyme (CeO2) and epidermal growth factor (EGF) as the core and poly(lactic-co-glycolic acid) (PLGA) as the shell via an emulsion electrospinning technique. An increase in the BSP content within the scaffolds corresponded to improved wound healing performance. These scaffolds exhibited increased hydrophilicity and porosity and improved mechanical properties and anti-UV properties. EBCP exhibited sustained release, and the degradation rate was <4 % in PBS for 30 days. The superior biocompatibility was confirmed by the MTT assay, hemolysis, and H&E staining. In addition, the in vitro results revealed that, compared with the other groups, the EBCP group presented excellent antioxidant and antibacterial effects. More importantly, the in vivo results indicated that the wound closure rate of the EBCP group reached 94.0 % on day 10 in the presence of H2O2. The results demonstrated that EBCP could comprehensively regulate the wound microenvironment, possess hemostatic abilities, and significantly promote wound healing. In conclusion, the EBCP is promising for facilitating the treatment of infected wounds and represents a potential material for clinical applications.
Molybdenum disulfide nanoflowers (MoS2 NFs) were prepared by hydrothermal method. The prepared MoS2 NFs was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), specific surface areas, Raman and X-ray photoelectron spectroscopy (XPS). The characterization results show that the flower-like spherical MoS2 is composed of many ultra-thin nanosheets with an average diameter of about 300-400 nm. MoS2 NFs also exhibits excellent UV-vis absorption and high fluorescence intensity. In order to explore the biological behavior of MoS2 NFs, the interaction between MoS2 NFs and bovine serum albumin (BSA) was studied by UV-Vis absorption, fluorescence, synchronous fluorescence spectra, and cyclic voltammetry. The results of absorption and fluorescence show that MoS2 NFs and BSA interact strongly through the formation of complexes in the ground state, and the static quenching is the main mechanism. The Stern-Volmer constant and the quenching constant was calculated about 3.79×107 L mol-1 and 3.79×1015 L mol-1 s-1, respectively. The synchronous fluorescence implied that MoS2 in the complex may mainly bind to tryptophan residues of BSA. The cyclic voltammograms indicated that the addition of BSA makes electron reduction of MoS2 NFs more difficult than the corresponding free state. The results show that hydrophobic forces play a major role in the binding interaction between BSA and MoS2 NFs.
临床药学是医药交叉融合的学科,是运用现代医药理论和技术,为患者提供最优的药物治疗方案,促进健康以及疾病预防的应用性学科.我国20世纪70年代末引入临床药学概念.随着生活水平的大幅提高,基因测序技术的飞速发展,生物信息与大数据科学的交叉应用,人们对医药服务要求越来越高,使临床药学从合理用药迅速扩展到精准药学、循证药学、新药临床发现与临床评价、医药大数据分析等更为广泛的领域[1],对临床药学服务以及临床药师的需求不断增加.
Depression is a chronic mental disorder which threatens human health and lives. However, the treatment of depression remains challenging largely due to blood brain barrier (BBB), which restricts drugs from entering the brain, resulting in a poor distribution of antidepressants in the brain. In this work, a novel brain-targeted drug delivery system was developed based on borneol-modified PEGylated graphene oxide (GO-PEG-BO). GO-PEG-BO was characterized and proved to possess excellent biocompatibility. By incorporating borneol, GO-PEG-BO could penetrate BBB efficiently by opening tight junctions and inhibiting the efflux system of BBB. The targeted distribution of GO-PEG-BO in the brain was observed by an in vivo biodistribution study. Moreover, GO-PEG-BO exhibited a neuroprotective effect, which is beneficial to the treatment of depression. Ginsenoside Rg1 (GRg1), which can relieve depressive symptoms but difficult to cross BBB, was loaded to GO-PEG-BO for the therapy of depression. In depressive rats, GRg1/GO-PEG-BO improved stress-induced anhedonia, despair and anxiety, and comprehensively relieved the depressive symptoms. In conclusion, GO-PEG-BO could serve as a promising nanocarrier for brain-targeted drug delivery, and provide a new strategy for the therapy of depression.
The immune-excluded tumors (IETs) show limited response to current immunotherapy due to intrinsic and adaptive immune resistance. In this study, it is identified that inhibition of transforming growth factor-β (TGF-β) receptor 1 can relieve tumor fibrosis, thus facilitating the recruitment of tumor-infiltrating T lymphocytes. Subsequently, a nanovesicle is constructed for tumor-specific co-delivery of a TGF-β inhibitor (LY2157299, LY) and the photosensitizer pyropheophorbide a (PPa). The LY-loaded nanovesicles suppress tumor fibrosis to promote intratumoral infiltration of T lymphocytes. Furthermore, PPa chelated with gadolinium ion is capable of fluorescence, photoacoustic and magnetic resonance triple-modal imaging-guided photodynamic therapy, to induce immunogenic death of tumor cells and elicit antitumor immunity in preclinical cancer models in female mice. These nanovesicles are further armored with a lipophilic prodrug of the bromodomain-containing protein 4 inhibitor (i.e., JQ1) to abolish programmed death ligand 1 expression of tumor cells and overcome adaptive immune resistance. This study may pave the way for nanomedicine-based immunotherapy of the IETs.
Total saponins of Panax ginseng (TSPG) have antidepressant effects. However, the underlying antidepressant mechanism of TSPG remains not clear. This study aimed to predict the mechanism of TSPG by bioinformatics analysis and to verify it experimentally. Bioinformatics analysis showed that the antidepressant effects of TSPG may be related to inflammation, and CX3CL1/CX3CR1 may play a key mediating role. Wistar rats were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks, and TSPG (50 mg/kg/d, 100 mg/kg/d) was administered throughout the modeling period. It was found that TSPG improves depressive behavior and reduces neuropathic damage in the hippocampus in rats. Meanwhile, TSPG decreased mRNA and protein expression of pro-inflammatory cytokines and CX3CL1/CX3CR1 and inhibited P38 and JNK protein phosphorylation in the hippocampus. Rat astrocytes were employed to explore further the potential mechanism of TSPG in regulating CX3CL1/CX3CR1. The results showed that CX3CL1 small interfering RNA (siRNA-CX3CL1) and CX3CR1 inhibitor (JMS-17-2) had similar effects to TSPG, that is, reduced inflammatory response, reactive oxygen species (ROS), and phosphorylation of P38 and JNK proteins, while overexpression of CX3CL1 (pcDNA-CX3CL1) counteracted the above effects of TSPG. It is suggested that the antidepressant effect of TSPG may be achieved through inhibition of CX3CL1/CX3CR1.
The dry root and rhizome of Panax ginseng C. A. Mey has garnered much interest owing to its medicinal properties against diabetes and cardiovascular diseases. In this study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS)-based metabolomics approach was used to illustrate the therapeutic mechanisms of ginseng extract on the serum and urinary metabolic profiles in streptozotocin-induced type 1 diabetes mellitus (T1DM) rats. Pharmacological and renal parameters in response to the administration of ginseng were also evaluated. In total, 16 serum endogenous metabolites and 14 urine endogenous metabolites, including pyruvic acid, indoleacetic acid, and phenylacetylglycine, were identified as potential biomarkers for diabetes. Pathway enrichment and network analysis revealed that the biomarkers modulated by ginseng were primarily involved in phenylalanine and pyruvate metabolism, as well as in arginine biosynthesis. Moreover, the levels of several renal injury-related biomarkers in T1DM rats were significantly restored following treatment with ginseng. The administration of the extract helped maintain tissue structure integrity and ameliorated renal injury. The findings suggest that the regulatory effect of ginseng extract on T1DM involves metabolic management of diabetic rats, which subsequently attenuates T1DM-induced early renal dysfunction.
The present study was to evaluate the chemo-photodynamic synergistic antitumor effect of FA-BSP-SA/TPGS micelles loaded with doxorubicin (Dox) and Zinc phthalocyanine (ZnPc). Multiple evaluation parameters involving quality index (particle size, zeta potential, loading capacity, and encapsulation efficiency, etc), biocompatibility, in vitro drug release, and in vitro antitumor assays were performed to explore the optimal mass ratio in FA-BSP-SA/TPGS mixed micelles. The results showed that FA-BSP-SA/TPGS25 micelles were more ideal carriers. The synergistic antitumor effect of Dox and ZnPc was also investigated and proved to be better. Moreover, the current study revealed that TPGS, Dox, and ZnPc decreased mitochondrial membrane potential and increased ROS level in breast 4T1 cancer cells. Meanwhile, in vivo antitumor assay certified that Dox@FA-BSP-SA/TPGS25+ ZnPc@FA-BSP-SA/TPGS25 micelles showed the most superior antitumor effect. In conclusion, Dox@FA-BSP-SA/TPGS25+ZnPc@FA-BSP-SA/TPGS25 micelles are promising drug-loaded nanomaterials with synergistic chemo-photodynamic effects against cancer.
以教学内容为载体,开展药剂学课程思政探索.深入挖掘药剂学课程蕴含的思政元素及两者间的融合点,建立有助于培养学生爱岗敬业、科学精神、科学思维、职业道德和工匠精神的思政案例库,使学生掌握药剂学基本知识和基本技能,引导学生形成良好的职业素养.