Advanced Science
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2025
·
IF 14.1
Jiaxin Yin,Shengcai Yang,Zengguang Liu,Songchen Zhao,Siyu Sun,Ziling Liu,Quanshun Li
The metabolic reprogramming of immunosuppressive tumor microenvironment (ITME) greatly influences the anti-tumor immunity. Bioinformatic analysis demonstrates that indoleamine 2,3-dioxygenase 1 and 3-hydroxy-3-methylglutaryl coenzyme A reductase (key enzymes of kynurenine (Kyn) and cholesterol metabolism, respectively), are overexpressed in human colon adenocarcinoma tissues. Herein, biomimetic and pH/ROS dual-responsive nanoparticles (PTSK@CRM) loaded with simvastatin and kynureninase (KYNase) are prepared to regulate Kyn and cholesterol metabolism, thereby enhancing the immunotherapeutic efficacy of PD-1 antibody (αPD-1). The monodisperse spherical PTSK@CRM is stable at pH 7.4, while it can release simvastatin and KYNase under low pH and high H 2 O 2 concentration. PTSK@CRM achieves excellently homologous tumor targeting to CT26 cells and induces cell apoptosis more effectively than PTSK. Moreover, PTSK@CRM significantly reduces the contents of Kyn and cholesterol and decreases the activation of the Kyn-AhR pathway in tumor metabolism. In vivo experiments show that PTSK@CRM possesses a favorable tumor-targeting ability to effectively suppress tumor growth and increase the infiltration of immune cells, including CD8 + T cells, CD4 + T cells, M1-like macrophages, and mature dendritic cells. Further, PTSK@CRM reduces the infiltration of immunosuppressive cells, thereby reversing ITME to improve the therapeutic efficacy of αPD-1. Overall, this immune-metabolic therapeutic strategy provides a potential route for remodeling ITME to enhance tumor immunotherapy.
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高影响因子
RSC Advances
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2024
·Vol. 14
·期 20
·13958-13971
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IF 3.9
Bin Wang,Yanbin Zhao,Yangyang Li,Junyan Yao,Shunjie Wu,Guoping Miu,Chenglin Chu
The insufficient osteogenesis of magnesium phosphate cement (MPC) limits its biomedical application. It is of great significance to develop a bioactive MPC with osteogenic performance. In this study, an injectable MPC was reinforced by the incorporation of a near infrared (NIR)-responsive nanocontainer, which was based on simvastatin (SIM)-loaded mesoporous silica nanoparticles (MSNs) modified with a polydopamine (PDA) bilayer, named SMP. In addition, chitosan (CHI) was introduced into MPC (K-struvite) to enhance its mechanical properties and cytocompatibility. The results showed that nanocontainer-incorporated MPC possessed a prolonged setting time, almost neutral pH, excellent injectability, and enhanced compressive strength. Immersion tests indicated that SMP-CHI MPC could suppress rapid degradation. Based on its physicochemical features, the SMP-CHI MPC had good biocompatibility and osteogenesis properties, as shown via in vitro and in vivo experiments. These findings can provide a simple way to produce a multifunctional MPC with improved osteogenesis for further orthopedic applications.
研究领域:
材料科学
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生物医学工程
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纳米技术
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药学
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Regenerative Biomaterials
·
2026
·
IF 8.7
Zhang Junjiang,Chang Yuqi,Zhou Yiwen,Zhou Yang,Li Jiayin,Wang Feng,Zhou Zhimin,Sui Lei,Li Yanjing
Maxillofacial bone defects present a major challenge in clinical practice. Bone graft and bone tissue engineering are limited by various side effects and potential risks, while local drug delivery is regarded as a convenient and efficient strategy for bone repair and regeneration. However, for bone tissue regeneration, drug delivery system should not only release osteogenic drugs, but also possess an appropriate morphology to provide structural support for cell proliferation and differentiation. Polymeric non-spherical counterparts may offer new osteogenic properties through altered cellular interactions, biodistribution, and immune responses, compared with spherical drug carriers. Poly(lactic-co-glycolic) acid (PLGA) has been widely used to prepare various drug carriers due to its excellent biocompatibility and controllable biodegradation. Shape regulation, surface modification, and drug incorporation are effective approaches to impart distinct functions to PLGA particles for various biomedical applications. However, PLGA has inherent limitations, including poor hydrophilicity, acidic degradation products, and a lack of functional ligands for cell attachment, which hinder its effectiveness in bone regeneration. To solve these problems, natural proteins were utilized to improve the bone/cartilage regeneration of polymeric particles/scaffolds through surface modification or physical complex due to their excellent biocompatibility and biodegradability.In this study, we successfully developed simvastatin (SIM)-loaded disc-shape PLGA microparticles with coarse surface (dPLGA) using W1/O/W2 followed by silk fibroin (SF) coating for hydrophilicity and biocompatibility improvement. In vitro and in vivo experiments revealed that SF-modified SIM-loaded dPLGA (SF-SIM@dPLGA) significantly promotes the osteogenic differentiation of stem cells and bone regeneration in cranial bone defects, indicating the superior osteoconductive and osteoinductive advantages arising from the physical morphology of particles and chemical effect. Additionally, SF-SIM@dPLGA demonstrated improved tissue adhesion and hemostatic ability. This novel PLGA non-spherical particle-based local delivery system provides a feasible strategy for practical maxillofacial bone repair due to the simple preparation procedures and enhanced bone regeneration performance.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Siyu Du,Yi Zheng,Yabing Chen,Yijing Guo,Xinyue Kang,Lei Wang
The growing incidence of periodontitis demands innovative therapies, as current drug treatments are limited by short retention times, rapid clearance, and the risk of antimicrobial resistance. This study introduces a novel pH-responsive nano-miclle system for simvastatin (SIM) delivery. Its core innovation lies in being the first system ((SIM NP)n) of its kind to be stabilized by a cross-linked "outer shell," which significantly enhances its stability and controlled release capabilities. This "smart" system remains stable in a neutral environment (pH 7.4), preventing premature drug release. However, upon encountering the acidic inflammatory microenvironment of periodontitis, the shell degrades, triggering the sustained release of SIM directly at the site of inflammation. In vitro studies demonstrated that the SIM-loaded micelles possess potent immunomodulatory effects: they effectively suppressed pro-inflammatory M1 macrophage polarization (decreasing IL-1β, iNOS) while promoting anti-inflammatory M2 macrophage polarization (increasing Arg-1, IL-10). Mechanistic investigation confirmed this therapeutic effect is mediated by the PI3K/AKT/mTOR signaling pathway. More importantly, in a mouse model of periodontitis, the nano-micelles significantly reduced alveolar bone resorption, demonstrating potent anti-inflammatory and bone-protective efficacy in vivo. In conclusion, this "smart" pH-triggered delivery system for SIM offers a highly promising and effective strategy to overcome the limitations of traditional therapies, providing a new targeted path for the treatment of periodontitis.
研究领域:
纳米医学
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牙科
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药物递送
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炎症
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生物材料
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CELLS TISSUES ORGANS
·
2018
·Vol. 205
·期 1
·20-31
·
IF 1.275
Li Yu,Zhang Zhanzhao,Zhang Zhiyong
The combination of bone tissue scaffolds with osteogenic induction factors is an effective strategy to facilitate bone healing processes. Here, chitosan (CS)/nano-hydroxyapatite (HA) scaffolds containing simvastatin (SIM)-loaded PLGA microspheres were fabricated by combining a freeze-drying technique with a modified water-oil-water emulsion method. The CS/HA weight ratio of 1:2 was selected by analyzing the effect of HA content on the micro-architecture, mechanical strength, and biocompatibility of the scaffold. Drug release kinetics showed that the SIM encapsulated in the scaffold was released in a sustained manner for up to 30 days. In vitro bioactivity study in rat bone marrow-derived mesenchymal stem cells showed that the SIM-loaded scaffolds had a strong ability in accelerating cell proliferation and inducing osteogenic differentiation. Moreover, an in vivo experiment using a rat calvarial defect model also documented that the SIM-loaded scaffolds had a remarkable effect on bone-promoting regeneration. The results of this study suggest that the SIM-loaded CS/HA scaffold is feasible and effective in bone repair and thus may provide a promising route for the treatment of critical-sized bone defects
研究领域:
生物材料学
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组织工程学
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药剂学
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APPLIED SPECTROSCOPY
·
2023
·
IF 3.5
Xinyuan Chen,Xiuzhi Chen,Hongyan Sun,Xiumin Li,Shizhao Ren,Can Jin,Hongjun Jin,Fenghua Chen,Rongrong Xue
Amorphous simvastatin (amorphous SIM) and Form I of SIM were prepared separately from SIM acetone (AC)/ethyl acetate (ETAC)/ethanol (ET) solutions by simply controlling the solvent evaporation rate, and the kinetic formation of amorphous SIM from SIM AC/ETAC/ET solutions was explained using mid-frequency Raman difference spectra analysis. The mid-frequency Raman difference spectra analysis results indicate that the amorphous phase has close connections with solutions and might be the bridge, playing an important role in the intermediate phase, between solutions and their outcome polymorphs.
研究领域:
药学
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材料科学
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光谱学
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Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 47
·9300-9311
·
IF 4.543
Zhao-Hui Huang,Peng-Fei Wei,Le Jin,Xiao-Qing Hu,Qing Cai,Xiao-Ping Yang
Nanomedicines have found promising applications in regulating the biological behaviors of cells because of the cell endocytosis effect. To enhance the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs), which is one of the key issues in relation to bone regeneration, a biodegradable simvastatin-bearing polyphosphazene prodrug was synthesized and made into nanoparticles (NPs). At the same time, photoluminescent tryptophan ethyl ester and hydrolyzable glycine ethyl ester were introduced as co-substituted side groups onto the polyphosphazene backbone. The resultant polymer, poly(simvastatin-co-ethyl tryptophanato-co-ethyl glycinato)phosphazene (PTGP-SIM), displayed the expected features of photoluminescence, degradability and sustained SIM release. Endocytosis of PTGP-SIM NPs by BMSCs and the location of internalized NPs, were visualized via the inherent photoluminescence features of PTGP-SIM. Thus, simvastatin was released inside the cells directly along with polymer degradation and could play a role in promoting osteogenic differentiation efficiently at quite a low local concentration. From the results, the present study suggested a very promising biomaterial for use as a flexible and functional carrier for bioactive components, which could find wide applications in relation to tissue regeneration.
研究领域:
纳米技术
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生物材料
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组织工程
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药学
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MOLECULES
·
2022
·Vol. 27
·期 21
·7158
·
IF 4.927
Lu Pan,Jiahao Yang,Lan Xu
Simvastatin (SIM) particles are liposoluble drugs with large particle sizes, resulting in poor compatibility with electrospun polycaprolactone (PCL)/polyethylene glycol (PEG) nanofibers, so that part of them will be exposed to the electrospun nanofiber surface, which is easy to cause the burst release of drugs. Therefore, in this paper, stearic acid (SA) with good biocompatibility was innovatively added to increase the dispersion uniformity of SIM in the spinning solution, thus improving the performances of SIM-loaded PCL/PEG nanofiber membranes (NFMs). Accordingly, the effects of SA addition on the morphologies, mechanical properties, wettability, and drug release properties of the SIM-loaded NFMs were studied. The results showed that after SIM was dissolved in SA solution, the particle size of SIM was significantly reduced and could be evenly dispersed in the polymer spinning solution, thus obtaining the SIM-loaded composite NFMs with the best morphology and performance.Keywords:electrospinning;simvastatin;composite nanofiber membranes;drug release
研究领域:
药学
·
材料科学
·
纳米技术
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Bioactive Materials
·
2022
·
IF 16.874
Tiantong Sun,Jie Huang,Wang Zhang,Xuanqi Zheng,Hong Wang,Jing Liu,Huijie Leng,Wanqiong Yuan,Chunli Song
Implant-associated infections (IAIs) caused by biofilm formation are the most devastating complications of orthopedic surgery. Statins have been commonly and safely used drugs for hypercholesterolemia for many years. Here, we report that simvastatin-hydroxyapatite-coated titanium alloy prevents biofilm-associated infections. The antibacterial properties of simvastatin against Staphylococcus aureus and Staphylococcus epidermidis biofilms in vitro was confirmed by crystal violet staining and live-dead bacterial staining. We developed a simvastatin-and hydroxyapatite (Sim-HA)-coated titanium alloy via electrochemical deposition. Sim-HA coatings inhibited Staphylococcus aureus biofilm formation and improved the biocompatibility of the titanium alloy. Sim-HA coatings effectively prevented Staphylococcus aureus IAI in rat femurs, as confirmed by radiological assessment and histological examination. The antibacterial effects of the Sim-HA coatings were attributed to their inhibitory effects on biofilm formation, as verified by scanning electron microscopic observations and bacterial spread plate analysis. In addition, the Sim-HA coatings enhanced osteogenesis and osteointegration, as verified by micro-CT, histological evaluation, and biomechanical pull-out tests. In summary, Sim-HA coatings are promising implant materials for protection against biofilm-associated infections.
研究领域:
骨科手术
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生物材料
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感染控制
·
生物医学工程
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JOURNAL OF CONTROLLED RELEASE
·
2026
·
IF 12.4
Muye He,Zhenze Xie,Ling Wang,Chengxiao Song,Dandan Chen,Bufang Fu,Jingguang Wang,Tao Wang,Wenxin Guo,Qianqian Han,Chang Du
Simvastatin, a traditionally recognized lipid-lowering medication, has emerged as a potent osteoinductive agent with significant potential in bone tissue engineering and regenerative medicine. Its advantages include multi-pathways enhancement of bone healing, potential application in special populations with osteoporosis (e.g., the elderly and pregnant women), high safety profile, and low cost. However, the clinical translation of simvastatin for bone regeneration has been challenged by its poor aqueous solubility, limited bioavailability when administered orally, and potential systemic side effects at higher doses. In this study, an osmotic pump system was developed as an innovative localized delivery carrier for simvastatin acid-loaded material, which could maintain therapeutic drug concentrations at the defect site for extended periods while minimizing systemic exposure. The approach mitigated the local inflammatory response caused by the burst release of simvastatin acid and enhanced the osteogenesis effect both in vitro and in vivo. This study represented the first application that loaded drugs with biomaterials through osmotic pump principle which is applicable to most materials loaded with water-soluble drugs, broadening the range of loadable drugs and their clinical application scope.
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CANCER SCIENCE
·
2022
·
IF 6.518
Jie Liu,Huxia Wang,Miao Zhang,Yazhao Li,Ruiqi Wang,He Chen,Bo Wang,Xiaoqian Gao,Shaoran Song,Yaochun Wang,Yu Ren,Juan Li,Peijun Liu
Multiple cancers have been reported to be associated with angiogenesis and are sensitive to anti‐angiogenic therapies. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. However, the underlying anticancer mechanisms of antiangiogenic drugs are still unknown. Metformin (MET) and simvastatin (SVA), two metabolic‐related drugs, have been shown to play important roles in modulating the hypoxic tumor microenvironment and angiogenesis. Whether the combination of MET and SVA could exert a more effective antitumor effect than individual treatments has not been examined. The antitumor effect of the synergism of SVA and MET was detected in mouse models, breast cancer patient‐derived organoids, and multiple tumor cell lines compared with untreated, SVA, or MET alone. RNA sequencing revealed that the combination of MET and SVA (but not MET or SVA alone) inhibited the expression of endothelin 1 (ET‐1), an important regulator of angiogenesis and the hypoxia‐related pathway. We demonstrate that the MET and SVA combination showed synergistic effects on inhibiting tumor cell proliferation, promoting apoptosis, alleviating hypoxia, decreasing angiogenesis, and increasing vessel normalization compared with the use of a single agent alone. The MET and SVA combination suppressed ET‐1‐induced hypoxia‐inducible factor 1α expression by increasing prolyl hydroxylase 2 (PHD2) expression. Furthermore, the MET and SVA combination showed a more potent anticancer effect compared with bosentan. Together, our findings suggest the potential application of the MET and SVA combination in antitumor therapy.
研究领域:
肿瘤学
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药理学
·
分子生物学
·
癌症生物学
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International Journal of Nanomedicine
·
2017
·
IF 4.3
Fei Tong,Bo Dong,Rongkui Chai,Ke Tong,Yini Wang,Shipiao Chen,Xinmei Zhou,Daojun Liu
The purpose of the research was to explore the therapeutic action of simvastatin-loaded poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) (PEG-b-PBLG50) on intestinal ischemia/reperfusion injury (II/RI) through downregulating bone morphogenetic protein 4 (BMP4)/cyclooxygenase-2 (COX-2) pathway as compared to free simvastatin (Sim). Sprague Dawley rats were preconditioned with 20 mg/kg Sim or simvastatin/PEG-b-PBLG50 (Sim/P) compounds, and then subjected to 45 min of ischemia and 1 h of reperfusion. The blood and small intestines were collected, serum levels of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α, and nitric oxide (NO) were checked, and the dry/wet intestine ratios, superoxide dismutase activity, myeloperoxidase content, reactive oxygen species, endothelial nitric oxide synthase, protein 47 kDa phagocyte oxidase (p47phox), BMP4, COX-2, and p38 mitogen-activated protein kinase (p38MAPK) expressions were measured in intestinal tissues. Both Sim and Sim/P pretreatment reduced intestinal oxidative damnification, restricted inflammatory harm, and downregulated the BMP4 and COX-2 expressions as compared to II/RI groups, while Sim/P remarkably improved this effect.
研究领域:
药理学
·
病理学
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高影响因子
危险品化学品经营许可证（带存储）