MATERIALS & DESIGN
·
2022
·
IF 9.417
Qiang Zhang,Kui Ma,Chun-Hei Lam,Ho-Pan Bei,Yu Liu,Xing Yang,Xin Zhao
Despite promise in preventing peritendinous adhesion, electrospun membranes face many challenges related to their complex fabrication process, untargeted/uncontrolled drug delivery and consequently low therapeutical effect. Here, a micro-and nano-environment dual-modulated barrier membrane (MNBM) with on-demand gene delivery capability is presented. Our MNBM is developed by first preparing extracellular signal-regulated kinase-2 (ERK2) siRNA-loaded gelatin methacryloyl (GelMA) nanogels via facile nano-emulsification technique, then incorporating these nanogels into poly-L-lactic acid (PLLA) fibers via simple blending electrospinning. The GelMA nanogels offer a nano-niche for ERK2-siRNA encapsulation and allow for a nano-environment controlled siRNA release by readily tuning the GelMA concentrations during nano-emulsification, while the resultant MNBM can mediate a micro-environment controlled siRNA delivery in response to the matrix metalloproteinase-2 (MMP-2) enriched micro-environment at the tendon repair site. Such MNBM can not only biologically orchestrate fibroblast behaviors by silencing the target gene expression, but also physically shield the tendon from extrinsic cell/tissue invasion. This study provides a proof-of-concept of anti-adhesion barrier membrane as an intelligent gene delivery system to offer a spatiotemporal and biophysical dual control over tendon recovery according to disease state and ensure long-term therapeutic efficacy. We envision such MNBM represents a promising therapeutic platform with great efficacy to achieve adhesion-free tendon repair.
研究领域:
生物医学工程
·
组织工程
·
基因治疗
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
OncoTargets and Therapy
·
2022
·
IF 4.345
Yue Jing,Gang Wang,Ying Ge,Minjie Xu,Shuainan Tang,Zhunan Gong
Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Jing Kuang,Zhi-Yong Rao,Di-Wei Zheng,Dong Kuang,Qian-Xiao Huang,Ting Pan,Hao Li,Xuan Zeng,Xian-Zheng Zhang
Glioblastomas (GBMs) are aggressive primary brain tumors with fatal outcome. Traditional chemo-radiotherapy has poor therapeutic effect and significant side effects, due to the drug and radiotherapy (RT) resistance, natural blood-brain barrier, and high-dose RT damage. Even more, tumor-associated monocytes (macrophages and microglia, TAMs) constitute up to 30%–50% of the GBM cellular content, and the tumor microenvironment (TME) in GBM is extremely immunosuppressive. Here, we synthesized nanoparticles (D@MLL) that hitchhike on circulating monocytes to target intracranial GBMs with the assistance of low-dose RT. The chemical construction of D@MLL was DOX·HCl loaded MMP-2 peptide-liposome, which could target monocytes by the surface modified lipoteichoic acid. First, low-dose RT at the tumor site increases monocyte chemotaxis and induces M1 type polarization of TAMs. Subsequently, the intravenous injected D@MLL targets circulating monocytes and hitchhikes with them to the central site of the GBM area. DOX·HCl was then released by the MMP-2 response, inducing immunogenic cell death, releasing calreticulin and high-mobility group box 1. This further contributed to TAMs M1-type polarization, dendritic cell maturation, and T cell activation. This study demonstrates the therapeutic advantages of D@MLL delivered by endogenous monocytes to GBM sites after low-dose RT, and it provides a high-precision treatment for GBMs.
研究领域:
肿瘤学
·
神经科学
·
药学
·
放射肿瘤学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2022
·Vol. 74
·期 9
·1241-1250
·
IF 4.81
Huang Wenwen,Zhou Xiaoying
ObjectivesTo examine the possible anti-histamine effects of dipotassium glycyrrhizinate (DG), a dipotassium salt of glycyrrhizic acid, on histamine-mediated lung fibroblast activation, differentiation and proliferation; to investigate the potential and underlying mechanisms for pulmonary fibrosis (PF) treatment.MethodsRat primary lung fibroblasts were extracted to establish cell models; histamine, DG and loratadine (LTD, a histamine receptor antagonist) were applied. Cell proliferation, migration and cell cycle were explored; intracellular signal proteins were detected; mitochondrial membrane potential was examined.Key findingsThe anti-histamine effects of DG were found in a similar pattern of LTD on lung fibroblasts. DG inhibited histamine-induced cell activation, proliferation and migration; DG altered histamine-mediated mitochondrial membrane potentials. DG reduced the histamine-induced PAR-2 (a tryptase receptor) expression to impair mast cell tryptase co-working. Histamine-induced expressions of MMP-2, FAK, TNF-α, P38, iNOS were decreased by DG, while Bax and caspase-3, P53 were increased by DG against histamine effects. Histamine drove cells from G0/G1 to S phases, whereas DG rested cells by inhibiting G0/G1 and G2/M phases.ConclusionsThis study provided the evidences that DG can inhibit histamine-induced effects on lung fibroblasts and promote apoptosis of abnormally activated lung fibroblasts, implicating its potential therapeutic mechanisms against PF development, also for those histamine-related diseases.
研究领域:
药理学
·
呼吸医学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Zhi Zheng,Zheng Guo,Fengmin Zhong,Bin Wang,Li Liu,Wei Ma,Cui-yun Yu,Hua Wei
The efficacy of myocardial regeneration strategies for myocardial infarction (MI) is significantly compromised by the complex structure and microenvironment of the myocardium. Although tissue engineering strategies based on cell therapy and/or pro-angiogenesis can somewhat improve cardiac function, the lack of proper myocardial materials that can withstand sustained deformability and adaptable mechanical properties severely affects myocardial wall integrity, systolic-diastolic cycles, and regeneration. Herein, we developed an integrated single “all-in-one” in situ dual crosslinking conductive hydrogel with favorable treatment properties termed as MaHA/B-G-SH/Fe 3+ by ionic interactions and chemical covalency based on modified hyaluronic acid (HA), gelatin (G), and Fe 3+ . The resulting dual crosslinking dynamic hydrogel not only provides self-healing and mechanical properties adapted to the myocardial systolic-diastolic cycle with simultaneous electrical signal transmission to fibrous islands and normal tissue, but also leads to significant increase of the myocardial wall thickness very close to that of normal myocardium upon one single injection with complete degradation within 28 days. Notably, the hydrogel covalently conjugated with a tailored peptide sequence of GGR-KLT and encapsulated with bone mesenchymal stem cells (BMSCs) was further used for in situ injection in a rat MI model, which exhibited (i) efficient inhibition of excessive matrix degradation dependent on early MMP-2 expression, (ii) triggered on-demand release of KLT for at least 14 days and significant promotion of angiogenesis, and (iii) synergistic BMSCs considerably enhanced myocardial regeneration within 28 days. Taken together, the dual crosslinking conductive hydrogel-mediated synergistic peptide and cell therapy provides comprehensive recovery and regeneration of the structure and function of the injured myocardium, thus demonstrating great potential for clinical translations.
研究领域:
组织工程
·
心血管医学
·
再生医学
·
生物医用材料
·
干细胞治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Wu Zhen,Zhang Peng,Yue Jie,Wang Qingshan,Zhuang Peipei,Jehan Shah,Fan Liyuan,Xue Jiarun,Zhou Wenhu,Wang Haiyang
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, while there is a lack of pharmaceutical interventions to halt AAA progression presently. To address the multifaceted pathology of AAA, this work develops a novel multifunctional gene delivery system to simultaneously deliver two siRNAs targeting MMP-2 and MMP-9. The system (TPNs-siRNA), formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates siRNAs during self-assembly. TPNs-siRNA safeguards siRNAs from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, and releases siRNAs to silence MMP-2 and MMP-9. Additionally, TPNs, serving as a multi-bioactive material, mitigates oxidative stress and inflammation, fosters M1-to-M2 repolarization of macrophages, and inhibits cell calcification and apoptosis. In experiments with AAA mice, TPNs-siRNA accumulated and persisted in aneurysmal tissue after intravenous delivery, demonstrating that TPNs-siRNA can be significantly distributed in macrophages and VSMCs relevant to AAA pathogenesis. Leveraging the carrier’s intrinsic multi-bioactive properties, the targeted siRNA delivery by TPNs exhibits a synergistic effect for enhanced AAA therapy. Furthermore, TPNs-siRNA is gradually metabolized and excreted from the body, resulting in excellent biocompatibility. Consequently, TPNs emerges as a promising multi-bioactive nanotherapy and a targeted delivery nanocarrier for effective AAA therapy.Graphical Abstract
研究领域:
纳米技术
·
基因治疗
·
血管生物学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2017
·
IF 6.32
Hong Cheng,Shi-Ying Li,Hao-Ran Zheng,Chu-Xin Li,Bo-Ru Xie,Ke-Wei Chen,Bin Li,Xian-Zheng Zhang
A novel single-molecular fluorescent probe was developed for spatiotemporal matrix metalloproteinase-2 (MMP-2) and caspase-3 imaging with distinct fluorescence signals. Due to the multi-Förster resonance energy transfer (FRET) processes, the probe could respond to MMP-2 and caspase-3 independently with high signal-to-noise ratio. Moreover, the overexpression of MMP-2 in cancer cell lines and the cisplatin induced cell apoptosis were spatiotemporal imaged with distinct fluorescence emissions. Because of the independent process of the probe for MMP-2 and caspase-3 imaging, the probe could meet the demands for precise disease diagnosis and cancer theranostic applications, which could extensively simplify the processes for precise cancer diagnosis and imaging.
研究领域:
生物医学工程
·
分子生物学
·
癌症研究
·
成像科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Ting-Ting He,Xin Li,Jie-Zhi Ma,Yuan Yang,Shiye Zhu,Jianhua Zeng,Lin Luo,Yu-Long Yin,Lin-Ying Cao
Triclocarban (TCC) and triclosan (TCS) have been detected ubiquitously in human body and evoked increasing concerns. This study aimed to reveal the induction risks of TCC and TCS on triple negative breast cancer through non-genomic GPER-mediated signaling pathways. Molecular simulation indicated that TCC exhibited higher GPER binding affinity than TCS theoretically. Calcium mobilization assay displayed that TCC/TCS activated GPER signaling pathway with the lowest observed effective concentrations (LOEC) of 10 nM/100 nM. TCC and TCS also upregulated MMP-2/9, EGFR, MAPK3 but downregulated MAPK8 via GPER-mediated signaling pathway. Proliferation assay showed that TCC/TCS induced 4 T1 breast cancer cells proliferation with the LOEC of 100 nM/1000 nM. Wound-healing and transwell assays showed that TCC/TCS promoted 4 T1 cells migration in a concentration-dependent manner with the LOEC of 10 nM. The effects of TCC on breast cancer cells proliferation and migration were stronger than TCS and both were regulated by GPER. TCC/TCS induced migratory effects were more significantly than proliferative effect. Mechanism study showed that TCC/TCS downregulated the expression of epithelial marker (E-cadherin) but upregulated mesenchymal markers (snail and N-cadherin), which was reversed by GPER inhibitor G15. These biomarkers results indicated that TCC/TCS-induced 4 T1 cells migration was a classic epithelial to mesenchymal transition mechanism regulated by GPER signaling pathway. Orthotopic tumor model verified that TCC promoted breast cancer in-situ tumor growth and distal tissue metastasis via GPER-mediated signaling pathway at human-exposure level of 10 mg/kg/d. TCC-induced tissue metastasis of breast cancer was more significantly than in-situ tumor growth. Overall, we demonstrated for the first time that TCC/TCS could activate the GPER signaling pathways to induce breast cancer progression.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Chunfang Qin,Hao Wang,Hongyan Cui,Yue Wang,Ming Zhang,Haidong Li,Yuchen Liu,Jingyun Wang,Qixian Chen,Yan Zhao
To overcome the biological barriers in the journey of systemic gene delivery, a multifaceted genomic synthetic nanomedicine was elaborated and strategically equipped with a multiple of intriguing responsiveness. Particularly, core–shell plasmid DNA condensates were created based on polyionic complexation with block copolymer of polyethylene glycol (PEG)-polylysine (PLys), namely, the nanoscaled PLys&pDNA nanoparticle tethered with the biocompatible PEG surroundings. Furthermore, redox-reversible disulfide crosslinking was introduced into PLys&pDNA nanoparticle to accomplish adequate structural stabilities, and thermal-responsive polypropylacrylamide (PNIPAM) was introduced as the secondary intermediate surroundings onto the pre-formulated PLys&pDNA nanoparticle with the aim of preventing the potential enzymatic degradation from the environmental nucleases. Hence, hundreds of times prolonged survival and retention was determined in pertinent to the blood circulation properties. Additionally, the installation of a guide ligand at the distal end of PEG segments was proposed to encourage selective tumor uptake. A linear peptide of GPLGVRG, which is selectively susceptible to digestion by the tumor-enriched matrix metalloproteinase 2 (MMP-2), was used as the linkage between the shell and core. This peptide has been shown to detach the bio-inert PEGylation, resulting in further facilitated cell endocytosis and intracellular trafficking activities. Hence, the precisely defined synthetic nanomedicine, which exhibits desirable characteristics, efficient expression of the therapeutic gene in the affected cells, and contributed to potent therapeutic efficacy in systemic treatment of intractable tumors by encapsulating the anti-angiogenic gene.
研究领域:
纳米技术
·
药学
·
癌症研究
·
基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Yahong Li,Junjin Zhu,Xin Zhang,Yuanyuan Li,Shu Zhang,Linxin Yang,Ruyi Li,Qianbing Wan,Xibo Pei,Junyu Chen,Jian Wang
It has been confirmed that substantial vascularization is an effective strategy to heal large-scale bone defects in the field of bone tissue engineering. The local application of deferoxamine (DFO) is among the most common and effective methods for promoting the formation of blood vessels, although its short half-life in plasma, rapid clearance, and poor biocompatibility limit its therapeutic suitability. Herein, zeolitic imidazolate framework-8 (ZIF-8) was selected as a vehicle to extend the half-life of DFO. In the present study, a nano DFO-loaded ZIF-8 (DFO@ZIF-8) drug delivery system was established to promote angiogenesis–osteogenesis coupling. The nanoparticles were characterized, and their drug loading efficiency was examined to confirm the successful synthesis of nano DFO@ZIF-8. Additionally, due to the sustained release of DFO and Zn2+, DFO@ZIF-8 NPs were able to promote angiogenesis in human umbilical vein endothelial cells (HUVECs) culture and osteogenesis in bone marrow stem cells (BMSCs) in vitro. Furthermore, the DFO@ZIF-8 NPs promoted vascularization by enhancing the expression of type H vessels and a vascular network. The DFO@ZIF-8 NPs promoted bone regeneration in vivo by increasing the expression of OCN and BMP-2. RNA sequencing analysis revealed that the PI3K-AKT-MMP-2/9 and HIF-1α pathways were upregulated by DFO@ZIF-8 NPs in HUVECs, ultimately leading to the formation of new blood vessels. In addition, the mechanism by which DFO@ZIF-8 NPs promoted bone regeneration was potentially related to the synergistic effect of angiogenesis–osteogenesis coupling and Zn2+-mediation of the MAPK pathway. Taken together, DFO@ZIF-8 NPs, which were demonstrated to have low cytotoxicity and excellent coupling of angiogenesis and osteogenesis, represent a promising strategy for the reconstruction of critical-sized bone defects.
研究领域:
骨组织工程
·
纳米技术
·
药学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Tong Shanshi,Yu Zhilong,Yin Fang,Yang Qilin,Chu Juhang,Huang Luyao,Gao Wenxue,Qian Mingping
Pancreatic cancer (PC) is one of the deadliest gastrointestinal malignancies. Advances in molecular biology and surgery have significantly improved survival rates for other tumors in recent decades, but clinical outcomes for PC remained relatively unchanged. Chemodynamic therapy (CDT) and Photothermal therapy (PTT) represent an efficient and relatively safe cancer treatment modality. Here, we synthesized Mn-doped Prussian blue nanoparticles (MnPB NPs) through a simple and mild method, which have a high loading capacity for drugs and excellent CDT/PTT effect. Cell line experiments in vitro and animal experiments in vivo proved the safety of MnPB NPs. We stimulated the PC cells with MnPB NPs and performed transwell migration assays. The migration of PC cells was reduced company with the decrease of two classical proteins: matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Moreover, MnPB NPs induced ferroptosis, which mediated the MAPK pathway and achieved tumor elimination in nude mice. This effective and safe strategy controlled by irradiation represents a promising strategy for pancreatic cancer.
研究领域:
肿瘤学
·
纳米技术
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 22
·7456-7470
·
IF 6.843
Xiangyu Meng,Jia Song,Yunfeng Lei,Xuezhong Zhang,Zhixin Chen,Zhuoxuan Lu,Liming Zhang,Zhifei Wang
Severe hypoxia in solid tumors limits the efficacy of oxygen (O2)-dependent photodynamic therapy (PDT). The overexpressed heat shock proteins (HSPs) in tumor cells hamper the effect of photothermal therapy (PTT). Herein, a tumor oxygenation-enhanced and ATP-reduced gelatin nanoreactor (MCGPD ∼ RGD NPs) for PDT/PTT-augmented combination cancer therapy is reported. In this nanosystem, the Arg-Gly-Asp (RGD) peptides of MCGPD ∼ RGD NPs can ensure accurate recognition and sufficient accumulation in the tumor site. After accumulation, doxorubicin (DOX) can be released from MCGPD ∼ RGD NPs in a mild acidic tumor microenvironment (TME) for highly efficient chemotherapy. Upon 808 nm laser irradiation, the overexpressed matrix metalloproteinase-2 (MMP-2) in the TME and the heat produced from the PDA coating trigger Gel NP degradation to expose chlorin e6 (Ce6) and Met from the cavity of MCGPD ∼ RGD NPs. The exposed Met elevates the O2 content and reduces ATP production in tumor sites to spur the successful O2-dependent PDT and HSP-mediated PTT. The heat generated by the PDA coating directly kills the tumor cells to ensure PTT and amplifies the chemotherapeutic effect. In vitro and in vivo assays indicate that MCGPD ∼ RGD NPs have excellent ability to promote cell apoptosis and to inhibit tumor growth. Overall, this smart responsive hydrogel nanosystem with hypoxia-relieving capacity and ATP-decreasing performance provides a promising strategy against cancer.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）