JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
Zhiwei Chen,Xinyu Di,Heyan Chen,Shengnan Song,Siyi Zhu,Leer Cai,Yuqi Han,Yongshuai Kang,Dingchao Shen,Huirong Huang,Aimin Cai,Hailun Zheng,Qing Yao,Maoping Chu,Ruijie Chen,Longfa Kou
Coronary artery lesions are a major complication of Kawasaki disease (KD), where the local microenvironment is marked by excessive oxidative stress and persistent inflammation, presenting significant challenges for effective treatment. M1-polarized macrophages dominate these lesions, releasing pro-inflammatory mediators that aggravate vascular injury. Regulating macrophage polarization from the M1 to M2 phenotype thus offers a promising therapeutic strategy. Here, we developed a reactive oxygen species (ROS)-responsive nanoplatform, HA-Sim@BRPL, to deliver simvastatin (Sim) specifically to inflamed coronary tissues. The nanocarrier is constructed from poly- l -lysine conjugated with bilirubin (BR), which self-assembles and enables ROS-triggered Sim release through BR's oxidative conversion to hydrophilic biliverdin. Surface decoration with hyaluronic acid (HA) facilitates selective uptake by CD44-expressing macrophages rather than cardiomyocytes. HA-Sim@BRPL effectively reduces intracellular ROS, promotes M2 macrophage polarization, and enhances endothelial cell survival via intercellular signaling. In a KD mouse model, HA-Sim@BRPL significantly attenuated coronary artery lesions and improved cardiac function. These results highlight a rationally designed nanomedicine that integrates oxidative stress responsiveness and inflammatory cell targeting, providing a promising therapeutic approach for coronary complications in KD.
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CHEMICAL ENGINEERING JOURNAL
·
2026
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IF 12.5
Duo Sun,Shihui Yang,Shuwei Qiao,Zhuoran Wang,Xiao Han,Sihan Ma,Heyi Gong,Jinghui Zhao,Fei Yan
3D-printed polyetheretherketone (PEEK) scaffolds hold great promise for personalized bone repair owing to their excellent mechanical properties and highly tunable porous architectures. However, their intrinsic bioinertness severely limits osseointegration and long-term clinical efficacy. We have developed an innovative bioactive scaffold (SIM@MPSP) by engineering a multifunctional biointerface onto 3D-printed porous PEEK. The biointerface consists of a polydopamine-anchored bimetallic (MgCu) metal-organic framework (MOF) coating that enables efficient loading and sustained release of simvastatin (SIM), Mg 2+ , and Cu 2+ . The coordinated release of these agents creates a therapeutically conducive microenvironment that promotes osteogenesis and angiogenesis, while reprogramming macrophages from a pro-inflammatory M1 phenotype to a pro-regenerative M2 state through modulation of both canonical and non-canonical NF-κB pathways. This immune-regulatory process effectively mitigates inflammation and rescues inflammatory suppression of osteogenesis, thereby establishing a favorable osteoimmunomodulatory niche. SIM@MPSP demonstrated excellent biocompatibility, significantly attenuated foreign-body responses, and enabled robust bone regeneration in in vivo models. Mechanistically, the scaffold facilitates deep bone growth throughout its porous network and forms an interlocked interface with native bone, thereby achieving robust osseointegration. This study presents a powerful biointerface engineering strategy for converting bioinert PEEK into a bioinstructive platform capable of orchestrating coordinated osteogenic, angiogenic, and immunomodulatory responses, thus offering new opportunities for personalized treatment of complex bone defects.
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Polymers
·
2026
·Vol. 18
·期 3
·398
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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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JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Xiaorong Kou,Xue Wu,Tao He,Liping Bai,Xinchao Li,Rui Luo,Yangsong Xu,Yixi Wang,Meiling Shen,Changyang Gong,Qinjie Wu
Temporary amelioration of immunosuppression following extrinsic stress-induced immunogenic signal release provides opportunities for immunotherapy improvement. However, therapeutics that fail to translate local stimulatory clues into ongoing systemic antitumor responses would in turn hijack the alleviated immune status toward tolerance, instead of immunity. Here, we constructed a tumor-activated precise dual-metabolic nanomodulator (RAISE) that induced extensive tumor cell death while supporting DCs functions, thus synergistically turning over tolerogenic tumor control and skewing an antitumor immunity. Sequentially responsive to tumor-overexpressing enzymes and high intracellular GSH, RAISE disintegrated in a self-destructive manner, which facilitated drug release and produced immunogenic tumor cell death associated with immunosuppression relief. Then, the regression of tolerogenic metabolism by RAISE replenished intratumoral CD103 + DCs, which further amplified T cell activation by enhancing antigen cross-presentation. Moreover, the blockade of indoleamine 2,3-dioxygenase activity restored the sensitivity of tumors to T cell immunity. Consequently, the cascade of immune activation helped to escape from the fate of tolerance and evolved into durable immune memory. RAISE exhibited efficient tumor control, and when combined with anti-PD-1 immunotherapy, RAISE inhibited lung metastasis, generated systemic immune responses, and induced immune memory. Taken together, RAISE can be utilized to trigger long-term systemic antitumor immunity for improving tumor immunotherapy.
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VACCINE
·
2023
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IF 5.5
Shuwen Xu,Zhiyong Wu,Gaofeng Cai,Yue Zhang,Song Peng,Lina Jiao,Zhenguang Liu,Yang Yang,Deyun Wang
Oil-in-water emulsion-based adjuvants have demonstrated acceptable safety in many disease indications, while their adjuvant activities for vaccines still need to be improved. Recently, the strategy of combining adjuvants with multiple types of immunostimulants has been shown to enhance immune responses. In this study, astragalus polysaccharides were combined with simvastatin as an immunostimulant to construct a compound O/W emulsion adjuvant. The formulations were optimized according to the OVA-specific antibody responses induced in mice. For this reason, high (5 mg/mL), medium (2.5 mg/mL), and low (1.25 mg/mL) concentrations of astragalus polysaccharides and high (10 mg/mL), medium (1 mg/mL), and low (0.1 mg/mL) concentrations of simvastatin were selected. The final optimal formulation of the immunostimulant was a high concentration of astragalus polysaccharides combined with a medium concentration of simvastatin. The optimal compound O/W emulsion adjuvant could induce effective humoral and cellular immune responses that were stronger and more stable than those induced by aluminum adjuvant and Freund's adjuvant. The OVA/HAPS-MSim-OE induced dramatically strong and persistent IgG expressions and Th1-polarized immune responses. What’s more, the highest CD4 + /CD8 + lymphocyte ratios were observed in OVA/HAPS-MSim-OE group. In addition, compound O/W emulsion adjuvant groups significantly promoted the secretion of IFN-γ and IL-6, which also indicated that the compound O/W emulsion adjuvants could induce both enhanced Th1 and Th2-mediated immune responses but prefer the Th1-mediated ones. This study would contribute to an interesting and promising direction in the development of emulsion-based adjuvants.
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ACS Nano
·
2022
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IF 18.027
Ling-Feng Zhang,Xing-Huan Wang,Cheng-Lu Zhang,Jaiwoo Lee,Bo-Wen Duan,Lei Xing,Ling Li,Yu-Kyoung Oh,Hu-Lin Jiang
During liver fibrogenesis, liver sinusoidal capillarization and extracellular matrix (ECM) deposition construct dual pathological barriers to drug delivery. Upon capillarization, the vanished fenestrae in liver sinusoidal endothelial cells (LSECs) significantly hinder substance exchange between blood and liver cells, while excessive ECM further hinders the delivery of nanocarriers to activated hepatic stellate cells (HSCs). Herein, an efficient nanodrug delivery system was constructed to sequentially break through the capillarized LSEC barrier and the deposited ECM barrier. For the first barrier, LSEC-targeting and fenestrae-repairing nanoparticles (named HA-NPs/SMV) were designed on the basis of the modification with hyaluronic acid and the loading of simvastatin (SMV). For the second barrier, collagenase I and vitamin A codecorated nanoparticles with collagen-ablating and HSC-targeting functions (named CV-NPs/siCol1α1) were prepared to deliver siCol1α1 with the goal of inhibiting collagen generation and HSC activation. Our in vivo results showed that upon encountering the capillarized LSEC barrier, HA-NPs/SMV rapidly released SMV and exerted a fenestrae-repairing function, which allowed more CV-NPs/siCol1α1 to enter the space of Disse to degrade deposited collagen and finally to achieve higher accumulation in activated HSCs. Scanning electronic microscopy images showed the recovery of liver sinusoids, and analysis of liver tissue sections demonstrated that HA-NPs/SMV and CV-NPs/siCol1α1 had a synergetic effect. Our pathological barrier-normalization strategy provides an antifibrotic therapeutic regimen.
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MATERIALS & DESIGN
·
2021
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IF 7.991
Mohammed A. Al-Baadani,Kendrick Hii Ru Yie,Abdullrahman M. Al-Bishari,Bilal A. Alshobi,Zixin Zhou,Kai Fang,Binwei Dai,Yiding Shen,Jianfeng Ma,Jinsong Liu,Xinkun Shen
The rising popularity of co-electrospinning technique in the field of biomaterial has enabled the possibility of combining various polymers, in which they provide the mechanical properties and the bioactivity for each other. Herein, a series of polycaprolactone/gelatin (PCL/Gel) composite membranes were prepared by co-electrospinning, and their biocompatibility and drug-controlled release ability were evaluated in detail for the first time. The addition of Gel significantly enhanced the adhesion and differentiation of osteoblasts, while the addition of PCL significantly improved the mechanical properties. Moreover, the in vitro degradation and drug release results showed that by adjust the PCL fibers amount and size, the degradation of Gel and the release profile of hydrophilic drugs/proteins could be effectively controlled: in the low PCL groups (PCL/Gel-1 & PCL/Gel-4), the Gel nano-fibers dissolved rapidly, resulting in an early explosive release within 1 week; however, with the increase of PCL content, the drug release rate decreased gradually, and the total release period could be extended to over 2 weeks (PCL/Gel-2, PCL/Gel-3 & PCL/Gel-5) or more (PCL/Gel-6). Therefore, the preparation of a controllable drug delivery system with good biological activity by co-electrospinning of PCL and Gel could provide an effective strategy for bone regeneration.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Xuejing Yang,Wenyu Cao,Xun Gu,Lijie Zheng,Qiuyue Wang,Yingying Li,Fang Wei,Tao Ma,Lu Zhang,Qingqing Wang
Currently, one of the main problems encountered in wound healing therapy is related to inefficient drug delivery. However, dissolving microneedles (DMNs) can be administered percutaneously to effectively deliver a drug to a deep wound area. Simvastatin (SIM) can promote wound healing, albeit its insolubility in water limits its application. Here, we designed a DMNs (SIM-NC@DMNs) drug delivery system loaded with SIM nanocrystals (SIM-NC) and evaluated its efficacy in wound healing. Based on our observations, the dissolution performance of insoluble SIM is significantly improved after the preparation of SIM-NC. For example, the saturation solubility of SIM-NC in deionized water and PBS increased by 150.57 times and 320.14 times, respectively. After the SIM-NC@DMNs are deeply inserted into the wound, the needle portion, which is composed of hyaluronic acid (HA), dissolves rapidly, and the SIM-NC loaded on the needle portion is efficiently released into the deep wound area for optimal therapeutic efficacy. The combination of NC and DMNs makes this system further effective for wound healing. Our cumulative work suggests that the newly developed SIM-NC@DMNs possess great potential in accelerating wound healing. By day 12 after treatment, the residual wound area in the Control group was 21.34 %, while the residual wound area in the SIM-NC@DMNs group was only 2.36 %. This result as well as provides certain evidence of its efficacy for wound healing therapy. The SIM-NC@DMNs drug delivery system may become an efficient treatment modality that promotes wound healing, with a promising potential in the field of wound healing research.
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International Journal of Nanomedicine
·
2023
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IF 8
Yulin Mo,Yanjun Yang,Jingqi Zeng,Weikun Ma,Yuxin Guan,Jingxi Guo,Xiaochun Wu,Dingkun Liu,Liang Feng,Xiaobin Jia,Bing Yang
Purpose Asperosaponin VI (ASP VI) as an active ingredient of Dipsacus asperoides, which has a wide range of biological and pharmacological activity. However, its development and application are restricted due to the poor gastrointestinal permeability and oral bioavailability. This investigation aims to reveal the influence of the self-assembled structure by the interaction between ASP VI and endogenous components NaTC and/or DOPC in the gastrointestinal environment on its biopharmaceutical properties, and novelty elucidated the molecular mechanism for the formation of self-assembled nanomicelles.Methods This change in phase state in gastrointestinal fluids is characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). UPLC-Q-TOF-MS was used to analyze the composition of phase components and the exposure of nanomicelles in vivo. Molecular dynamics simulation (MDS) was applied to preliminarily elucidate the self-assembly mechanism of ASP VI in the gastrointestinal environment. Furthermore, theS8 promoting absorption mechanism of nanomicelles were investigated through in vivo pharmacokinetic experiments, parallel artificial membrane permeability assay (PAMPA), quadruple single-pass intestinal perfusion in rats, and Caco-2 cell monolayer model.Results We demonstrated that the ASP VI could spontaneously form dynamic self-assembled structures with sodium taurocholate (NaTC) and dipalmitoyl phosphatidylcholine (DOPC) during gastrointestinal solubilization, which promoted the gastrointestinal absorption and permeability of ASP VI and increased its exposure in vivo, thus improving the biopharmacological characteristics of ASP VI. Moreover, ASP VI-NaTC-DOPC-self-assembled nanostructures (ASP VI-NaTC-DOPC-SAN) manifested higher cellular uptake in Caco-2 cells as evidenced by flow cytometry and confocal microscopy, and this study also preliminarily revealed the mechanism of self-assembly formation of ASP VI with endogenous components NaTC and DOPC driven by electrostatic and hydrogen bonding interactions.Conclusion This study provides evidence that the dynamic self-assembled phase transition may play a key role in improving the biopharmacological characteristics of insoluble or low permeability active ingredients during the gastrointestinal dissolution of Chinese medicines.
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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.
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ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Xiaojie Xu,Jiahui Zuo,Huajing Zeng,Yuan Zhao,Zengjie Fan
The bioinertness, poor antibacterial properties, and weak osseointegration of polyether-etherketone (PEEK) limit its clinical application as oral implants. In this study, it is developed a personalized and customizable PEEK implant with multifunctional capabilities through sequential 3D printing, surface sulfonation (SPEEK), and modification using a drug-loaded photocured hydrogel composed of acrylic acid-acrylamide (AA-AM) containing simvastatin-cefepime (SIM-CFP). The modified implant, referred to as SCHSPEEK, mimics the structure of biomimetic periodontal ligament (PDL) fibers. The chemical composition, surface characteristics, and biological properties of SCHSPEEK both in vitro and in vivo are systematically investigated. The results demonstrate that hydrogel modification not only enhances hydrophilicity and reduces surface roughness and friction coefficient, but also improves biocompatibility, drug release, and antibacterial efficacy. Importantly, SCHSPEEK exhibits a significant improvement in osseointegration capacity in vivo. These findings highlight the potential of SCHSPEEK implants to serve as promising orthopedic and dental implants in clinical settings.
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BIOMATERIALS
·
2023
·
IF 14
Yanbin Zhao,Peng He,Junyan Yao,Mei Li,Bin Wang,Linyuan Han,Zhihai Huang,Chao Guo,Jing Bai,Feng Xue,Yu Cong,Weihua Cai,Paul K. Chu,Chenglin Chu
Although biodegradable polymer coatings can impede corrosion of magnesium (Mg)-based orthopedic implants , they are prone to excessive degradation and accidental scratching in practice. Bone implant-related infection and limited osteointegration are other factors that adversely impact clinical application of Mg-based biomedical implants. Herein, a self-healing polymeric coating is constructed on the Mg alloy together with incorporation of a stimuli-responsive drug delivery nanoplatform by a spin-spray layer-by-layer (SSLbL) assembly technique. The nanocontainers are based on simvastatin (SIM)-encapsulated hollow mesoporous silica nanoparticles (S@HMSs) modified with polydopamine (PDA) and polycaprolactone diacrylate (PCL-DA) bilayer . Owing to the dynamic reversible reactions, the hybrid coating shows a fast, stable, and cyclical water-enabled self-healing capacity. The antibacterial assay indicates good bacteria-killing properties under near infrared (NIR) irradiation due to synergistic effects of hyperthermia, reactive oxygens species (ROS), and SIM leaching. In vitro results demonstrate that NIR laser irradiation promotes the cytocompatibility, osteogenesis, and angiogenesis . The coating facilitates alkaline phosphatase activity and expedites extracellular matrix mineralization as well as expression of osteogenesis-related genes. This study reveals a useful strategy to develop multifunctional coatings on bioabsorbable Mg alloys for orthopedic implants .
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