ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Runze Zhao,Xiaoyue Ning,Mengqi Wang,Huanhuan Wang,Guang Xing,Li Wang,Chengzhi Lu,Ao Yu,Yongjian Wang
Nanoprodrugs with responsive release properties integrate the advantages of stimuli-responsive prodrugs and nanotechnology. They would provide ultimate opportunity in fighting atherosclerosis. In this study, we synthesized a redox-responsive nanoprodrug of simvastatin (TPTS) by conjugating α-tocopherol polyethylene glycol derivative to the pharmacophore of simvastatin with a thioketal linker. TPTS formed nanoparticles and released parent simvastatin in the presence of hydrogen peroxide. Moreover, by taking advantage of the self-assembly behavior of TPTS, we developed a fibronectin-targeted delivery system (TPTS/C/T) to codelivery simvastatin prodrug and ticagrelor. In vitro and in vivo experiments indicated that TPTS and TPTS/C/T had good stability, which could reduce off-target leakage of drugs. They greatly inhibited the M1-type polarization of macrophages; reduced intracellular reactive oxygen species level and inflammatory cytokine; and TNF-α, MCP-1, and IL-1β were secreted by macrophage cells, thus providing enhanced anti-inflammatory and antioxidant effects compared with free simvastatin. TPTS/C/T realized targeted drug release to plaques and synergistic therapeutic effects of simvastatin and ticagrelor on atherosclerosis treatment in an ApoE–/– mouse model, resulting in excellent atherosclerosis therapeutic efficacy and a promising biosafety profile. Therefore, this study provides a new method for manufacturing statin nanodrugs and a new design idea for related responsive drug release nanosystems for atherosclerosis.
研究领域:
药学
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纳米技术
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心血管疾病
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药物递送系统
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Lu Zhang,Huan Shen,Boheng Liu,Tingting Liu,Yun Mei,Bin Li,Yang Liu,Gang Cao,Shuo Yu
Hepatic fibrosis, primarily driven by the sustained activation of hepatic stellate cells (HSCs), continues to pose a significant global health challenge due to the scarcity of effective therapeutic interventions. Existing single-target approaches are inadequate in addressing the complex multicellular regulatory network within the fibrotic niche, where injured hepatocytes, Kupffer cells (KCs), and capillarized liver sinusoidal endothelial cells (LSECs) collectively perpetuate HSC activation through paracrine signaling mechanisms. To address this challenge, a novel nanoplatform has been developed, comprising a co -delivery system of quercetin (Que) and simvastatin (Sim) within a mesoporous polydopamine (MPDA)-based matrix, designed to achieve the synchronized modulation of multicellular interactions. The MPDA carrier possesses intrinsic liver-targeting and reactive oxygen species (ROS)-scavenging properties, facilitating preferential accumulation in fibrotic lesions and the mitigation of oxidative stress originating from hepatocytes and KCs. In the acidic fibrotic environment, Que and Sim are sustained within the system due to the acid-responsive properties of MPDA. The released Que reprograms pro-inflammatory M1 macrophages into anti-inflammatory M2 phenotypes, while Sim reverses LSEC capillarization, collectively disrupting the microenvironmental factors driving HSC activation. Moreover, all components—MPDA, Que, and Sim—can directly inhibit HSC activation through complementary pathways. This multi-target strategy resulted in a more significant reduction in collagen deposition compared to monotherapies in preclinical models, alongside a notable restoration of liver function. By integrating microenvironmental reprogramming with the interception of multicellular networks, our study establishes a paradigm-shifting nanotherapeutic approach for reversing fibrosis and underscores the potential of engineered multidrug coordination in treating complex stromal diseases.
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DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Chenghui Qian,Yubo Liu,Si Chen,Chenyang Zhang,Xiaohong Chen,Yuehua Liu,Ping Liu
Introduction: Drugs and biocompatible nanoparticles have raised significant potential in advancing the bone regeneration. Electrospinning technology enables the full realization of the value of drugs and nanoparticles. Methods: In this study, we have successfully fabricated core–sheath nanofibers solely composed of polycaprolactone (PCL) polymer. Simvastatin (SIM) was confined to the core of the nanofibers while nanohydroxyapatite (nHA) was loaded on the nanofiber surface. Results: All the prepared nanofibers exhibited a cylindrical micromorphology, and the core–sheath structure was exploited using a Transmission Electron Microscope. X-ray pattern results indicated that SIM was in an amorphous state within nanofibers, while Fourier Transform InfraRed spectroscopy showed excellent chemical compatibility among SIM, nHA, and PCL. The actual loading of nHA within the nanofiber was determined by a thermogravimetric test due to the high melting point of nHA. Core–sheath nanofibers could release SIM for 672 h, which was attributed to the core–sheath structure. Furthermore, nanofibers loaded with SIM or nHA had a positive impact on cell proliferation, with the core–sheath nanofibers displaying the most favorable cell proliferation behavior. Discussion: Such a synergistic facilitation strategy based on materials and nanostructure may encourage researchers to exploit new biomedical materials in future.
研究领域:
生物医学工程
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材料科学
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组织工程
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DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2018
·Vol. 8
·期 5
·1090-1102
·
IF 3.395
Xie Yonghui,Liu Chenchen,Huang Hongwei,Huang Jian,Deng Aiping,Zou Ping,Tan Xueying
This study aimed to investigate the improved therapeutic efficacy and pharmacokinetic profiles of simvastatin (SIM) with imparted bone targeting potential using tetracycline-mediated PEG-PLGA (TC-PEG-PLGA) micelles in osteoporotic rats. The SIM-loaded TC-PEG-PLGA (TC-PEG-PLGA/SIM) micelles were evaluated for particle size, morphology, stability, loading efficiency, cell viability, bone mineral binding ability in vitro, mineralization, pharmacokinetics, and pharmacodynamics. TC-PEG-PLGA conjugates were successfully and could self-assembly form micelles in aqueous medium with a 19.4 μg/mL critical micelle concentration. Then, TC-PEG-PLGA/SIM micelles were prepared with solvent diffusion method, and the obtained micelles (56.21 ± 7.39 nm average size; 81.8 ± 3.1% encapsulation efficiency; and 7.56 ± 0.27% drug loading) led to the prolonged release of SIM from micelles. Cellular uptake test indicated that TC had no effects on micellar internalization and micellar internalization was mainly involved with clathrin-mediated endocytic pathway. In vivo pharmacokinetic results indicated that TC-PEG-PLGA/SIM micelles exhibited a significantly prolonged time in systemic circulation and were preferentially accumulated in bone tissue. TC-PEG-PLGA/SIM micelles showed better therapeutic effects, as reflected by the improved bone mineral density, bone mineral content, and bone mechanical strength. Overall, these results suggested that TC-PEG-PLGA/SIM micelles provide several advantages, including prolonged systemic circulation, enhanced bone tissue distribution, and improved therapeutic outcomes in osteoporotic rats.
研究领域:
药剂学
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骨科学
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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2010
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IF 2.962
Yanzhuo Zhang,Jinghai Zhang,Tongying Jiang,Siling Wang
The purpose of this study was to develop spherical mesocellular foam (MCF) loaded with a poorly water-soluble drug, intended to be orally administered, able to improve the dissolution rate and enhance the drug loading capacity. Spherical MCF with a continuous 3-D pore system was synthesized using Pluronic 123 triblock polymer (P123) as a surfactant coupled with cetyltrimethyl ammonium bromide (CTAB) as a co-surfactant. A model drug, simvastatin (SV), was loaded onto spherical MCF via a procedure involving a combination of adsorption equilibrium and solvent evaporation . The drug release rate and the drug loading efficiency of spherical MCF were compared with those of fibrous SBA-15. Investigations using nitrogen adsorption , scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and HPLC demonstrated the successful incorporation of SV into the MCF host. It was found that spherical MCF has a high drug loading efficiency up to 37.5%, and higher than that of fibrous SBA-15 with a pore diameter of 6.5 nm. It is worth noting that fast release rate of SV was obtained from spherical MCF compared with SBA-15 and pure crystalline SV using enzyme-free simulated intestinal fluid (SIF, pH 6.8).
研究领域:
药剂学
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纳米技术
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药物递送
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材料科学
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生物医学工程
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DOI
高影响因子
Cell Death Discovery
·
2026
·
IF 10.4
Yin Shilin,Yang Fang,Zhang Zhiwei,Liu Mingyuan,Tang Hong,Yang Kai
Dysregulation of cholesterol homeostasis is closely associated with the development of various cancers, but the underlying mechanisms remain unclear. This study found that the circadian clock gene Period 2 (PER2) is downregulated in oral squamous cell carcinoma (OSCC), promoting intracellular cholesterol synthesis and cell proliferation. Conversely, PER2 overexpression inhibits cell proliferation by suppressing intracellular cholesterol synthesis. Mechanistically, PER2 binds to Myosin Heavy Chain 9 (MYH9) and recruits Tripartite Motif Containing-21 (TRIM21) to promote ubiquitin-dependent degradation of MYH9, thereby inhibiting the cholesterol synthesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), reducing intracellular cholesterol synthesis, and suppressing OSCC proliferation. In OSCC xenograft models, overexpression of PER2 or treatment with the HMGCR inhibitor simvastatin significantly inhibited OSCC growth, with the combination showing markedly enhanced anti-OSCC efficacy compared to either approach alone. To explore the circadian regulatory role of PER2, overexpression or silencing experiments in OSCC demonstrated that PER2 modulates the circadian rhythms of HMGCR expression, intracellular cholesterol, and cell proliferation. Further investigations in subcutaneous OSCC mouse models revealed sex-specific circadian rhythms in PER2 and HMGCR expression, intracellular cholesterol, cell proliferation, and tumor growth in OSCC cells. Specifically, the acrophases of these indicators in OSCC of male mice were delayed relative to females, and the mesors of HMGCR expression, intracellular cholesterol, and cell proliferation were significantly higher than in females. The anticancer efficacy of simvastatin against OSCC in mice varied up to 2.5-fold across six different time points within 24 h, with broader time windows for optimal therapeutic efficacy and adverse effects in female mice than in males. This study identified a novel mechanism by which PER2 reprograms intracellular cholesterol, demonstrating that PER2 upregulation combined with simvastatin represents a potential novel strategy to improve the prognosis of OSCC patients, and clarifies that the anti-OSCC effect of simvastatin exhibits time-dependent and sex differences.
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DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
·
2023
·
IF 8.3
Wei Peng,Yufeng Qian,Xuchen Qi
Glioma is the most common primary malignant tumor of the nervous system that starts in the glial cells. Its high invasiveness and recurrence pose major challenges to its effective treatment. Ferroptosis is a new type of programmed cell death characterized by intracellular iron overload and accumulation of lipid peroxides. Existing studies have demonstrated the efficacy of targeted ferroptosis therapy in the treatment of glioma. In this study, folic acid (FA)-modified layered double hydroxide loaded with simvastatin (SIM), a ferroptosis drug, was used to prepare a novel ferroptosis nanodrug (FA-LDH@SIM). The prepared nanodrug improved the therapeutic effect of SIM on glioma. Compared with free SIM, FA-LDH@SIM showed greater cytotoxicity, significantly inhibited glioma cell proliferation, and significantly inhibited glioma invasion and migration ability. Furthermore, SIM could induce changes in certain ferroptosis indicators, including increased intracellular LPO, ROS and MDA level, decreased GSH production, increased divalent iron level, and changes in mitochondrial morphology. Further experiments revealed that SIM induced ferroptosis in tumor cells by down-regulating HMGCR expression and inhibiting the mevalonate pathway to down-regulate GPX4 expression. In addition, the FA-LDH@SIM group significantly inhibited tumor growth after treatment in the animal glioma model. These results indicate that the FA-LDH@SIM nanodrug delivery system exhibits excellent anti-tumor effects both in vitro and in vivo , and is an effective method for the treatment of glioma.
研究领域:
肿瘤学
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药理学
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纳米技术
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 11
Shengdan Zhang,Wen Zhang,You Wang,Miao Yin,Shuai Lu,Wei Li,Bo Cheng
Diabetic periodontitis remains a formidable clinical challenge characterized by persistent infection, oxidative stress, and impaired alveolar bone regeneration. Here, we have developed an engineered core-shell microneedle (MN) patch that enables the staged release of doxycycline and simvastatin to achieve coordinated antibacterial and osteogenic effects within periodontal lesions. The outer polyvinyl alcohol (PVA) shell rapidly dissolves upon insertion into gingival tissue, enabling burst release of doxycycline for immediate bacterial eradication. Subsequently, the polyvinylpyrrolidone (PVP) core, loaded with simvastatin-encapsulated polydopamine nanoparticles (Sim@PDA NPs), provides sustained release, leveraging the intrinsic reactive oxygen species (ROS)-scavenging capacity of PDA to mitigate local oxidative stress and promote osteogenic differentiation. A silk fibroin backing layer ensures long-term doxycycline release, preventing bacterial recolonization and maintaining a regenerative microenvironment. In vitro , Doxy/SIM-MNs exhibited potent antibacterial and antibiofilm activity against Porphyromonas gingivalis and Staphylococcus aureus , excellent cytocompatibility, and robust induction of alkaline phosphatase activity, mineralized nodule formation, and osteogenic gene expression in mesenchymal stem cells. In a rat model of diabetic periodontitis, Doxy/SIM-MNs markedly reduced inflammatory destruction, enhanced alveolar bone regeneration, and reestablished periodontal homeostasis by relieving negative regulation of Wnt signaling while suppressing NF-κB signaling and apoptosis. This hierarchically staged microneedle platform offers a clinically translatable strategy for the integrated management of infection, inflammation, and bone regeneration in diabetes-associated periodontitis and other chronic inflammatory bone diseases.
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2018
·
IF 7.877
Xiaopeng Mo,Zening Zheng,Yang He,Huihai Zhong,Xuejia Kang,Mingjie Shi,Tuanbing Liu,Zheng Jiao,Yongzhuo Huang
Effective treatment of malignant glioma still remains a formidable challenge due to lack of the effective BBB-permeable drugs and efficient brain delivery methods, and the pharmacotherapy options are very limited. Therefore, to develop an effective therapeutic strategy is a pressing need. In this work, a noncytotoxic drug combination (i.e., simvastatin and fenretinide) was revealed to be potent for treating glioma, which was co-encapsulated into a TPGS-TAT-embedded lactoferrin nanoparticle system for achieving brain-targeted biomimetic delivery via the LRP-1 receptor. It was shown that the lactoferrin nanoparticle repolarized the tumor-associated macrophages from the M2 phenotype to M1 via regulating the STAT6 pathway, as well as induced the ROS-mediated mitochondrial apoptosis by inhibiting the Ras/Raf/p-Erk pathway in the glioma cells. The antiglioma efficacy was further demonstrated in both the subcutaneous and orthotopic glioma models. The repolarization of tumor-associated macrophages not only prompted the ROS generation but also induced the innate immunity (e.g., antitumor cytokine release). This delivery and therapeutic strategy provides a novel modality for the glioma treatment.
研究领域:
神经肿瘤学
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药理学
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纳米医学
·
癌症生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Bionic Engineering
·
2022
·Vol. 19
·期 6
·1645-1657
·
IF 2.995
Liu Chang,Deng Dan,Gao Jing,Jin Shue,Zuo Yi,Li Yubao,Li Jidong
The ideal Guided Bone Regeneration (GBR) membrane is required to have good biocompatibility, space maintenance ability, appropriate degradation rate, and preferably can guide the regeneration of vascularized bone tissue. In this study, Simvastatin (SIM) and calcium Phosphate (CaP) were encapsulated in a Polycaprolactone (PCL)/Chitosan (CS) core–shell structural fibrous membranes via coaxial electrospinning technology. The results showed that loaded SIM in the core of the core–shell structure fibrous membranes could sustainably release the drug for more than two months and upregulate the angiogenic marker of Bone Mesenchymal Stem Cells (BMSCs). Adding a certain amount of CaP to the shell layer provided more sites for the mineralization and synergistic with SIM to promote osteogenic differentiation of BMSCs in vitro. The intramuscular implantation experiments in rabbits suggested a normal early inflammation and enhanced vascularization induced by the SIM-loaded fibrous membranes. This study proposed an effective strategy to prepare a dual-loaded core–shell fibrous membrane for guided vascularized bone tissue regeneration.
研究领域:
生物材料
·
组织工程
·
再生医学
·
药剂学
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产品关联
DOI
高影响因子
Polymers
·
2026
·Vol. 18
·期 3
·398
·
IF 5.8
Wanqing Zhan,Qiqi Wen,Haiyan Yao,Junchao Wei
Insufficient osteogenic activity and mechanical properties of poly-L-lactic acid (PLLA) are urgent problems to be solved in deepening their application in bone tissue engineering. In this work, PLLA/mesoporous bioactive glass (PLLA/MBG) scaffolds and PLLA/simvastatin-loaded mesoporous bioactive glass (PLLA/MBG@SIM) scaffolds with filler content of 5, 10, and 15 wt% MBG and MBG@SIM were fabricated via electrospinning technology. At 10 wt% MBG loading, the tensile strength and tensile modulus were 3.23 ± 0.26 MPa and 124.47 ± 8.68 MPa, respectively, over 50% higher than those of PLLA scaffolds, demonstrating a significant enhancement in mechanical properties. Moreover, the incorporation of MBG improved the bioactivity of the PLLA scaffold, promoting the formation of apatite on the surface of the scaffolds. All composite scaffolds were non-toxic with good biocompatibility. Furthermore, PLLA/MBG@SIM composite scaffolds displayed superior osteogenic effects, better than the pure PLLA scaffolds and PLLA/MBG scaffolds. This work presents a multifunctional scaffold system combining enhanced mechanical strength with potent osteogenic activity, showing great promise for bone tissue engineering applications.
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DOI
PubMed
高影响因子
Materials Today Bio
·
2022
·
IF 10.761
Xiaojing Yuan,Zuoying Yuan,Yuanyuan Wang,Zhuo Wan,Xiaotong Wang,Shi Yu,Jianmin Han,Jianyong Huang,Chunyang Xiong,Lihong Ge,Qing Cai,Yuming Zhao
Dental pulp necrosis are serious pathologic entities that causes tooth nutrition deficiency and abnormal root development, while regeneration of functional pulp tissue is of paramount importance to regain tooth vitality. However, existing clinical treatments, which focus on replacing the necrotic pulp tissue with inactive filling materials, fail to restore pulp vitality and functions, thus resulting in a devitalized and weakened tooth. Currently, dental pulp regeneration via stem cell-based therapy for pulpless teeth has raised enormous attention to restore the functional pulp. Here, a novel design of injectable simvastatin (SIM) functionalized gelatin methacrylate (GelMA) cryogel microspheres (SMS) loaded with stem cells from human exfoliated deciduous teeth (SHEDs) was established to refine SHEDs biological behaviors and promote in vivo vascularized pulp-like tissue regeneration. In this system, SIM encapsulated poly (lactide- co -glycolide) (PLGA) nanoparticles were incorporated into GelMA cryogel microspheres via cryogelation and O 1 /W/O 2 emulsion method. SMS with sustained release of SIM promoted SHEDs adhesion, proliferation and exhibited cell protection properties during the injection process. Furthermore, SMS enhanced SHEDs odontogenic differentiation and angiogenic potential, and SHEDs loaded SMS (SHEDs/SMS) are beneficial for human umbilical vein endothelial cells (HUVECs) migration and angiogenesis, demonstrating their potential for use in promoting vascularized tissue regeneration. SHEDs/SMS complexes were injected into cleaned human tooth root segments for subcutaneous implantation in nude mice. Our results demonstrated that SHEDs/SMS could induce vessel-rich pulp-like tissue regeneration in vivo and that such an injectable nano-in-micro multistage system for the controlled delivery of bioactive reagents would be suitable for clinical application in endodontic regenerative dentistry.
研究领域:
牙科学
·
组织工程
·
再生医学
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干细胞生物学
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材料科学
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DOI
PubMed
高影响因子
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