MATERIALS & DESIGN
·
2022
·
IF 9.417
Zhenyu Yang,Xueqiao Yu,Pengfei Wei,Yiqian Huang,Shuai Zhou,Wei Jing,Yan Zhang,Liya Sun,Guoqiang Bao,Xianli He,Bo Zhao
Pancreatic leakage is severe and life-threatening when happening pancreatitis or conducting pancreatectomy on patients, which easily induces bleeding, infection and even death. Commercial tissue adhesives cannot meet the demands for pancreatic leakage sealing due to the weak adhesiveness, potential toxicity and inability to degrade. Few reports have been feasibly paid attention to pancreas sealants due to the complicated conditions such as enzymatic microenvironments, mechanical dynamics and pre-infections. Herein, we prepared a rapid high-adhesion, antibacterial, biodegradable and injectable bioadhesive based on the FDA-approved polyethylene glycol to seal the pancreatic leakage for clinical translations and commercial applications. The tetra-armed poly(ethylene glycol) succinimidyl glutarate (PEG-SG), tetra-armed poly(ethylene glycol) amine (PEG-NH 2 ) and tannic acid (TA) were integrated to rapidly form the adhesive hydrogel (gelling time < 5 seconds) for convenient operations, while this bioadhesive achieved tough tissue adhesion (∼ 30 kPa), robust antibacterial activity (∼ 95% efficiency) and biocompatibility, revealing the excellent performances for pancreatic wound closure. In the established pre-clinical pancreatectomy using Bama miniature pig model, the bioadhesive presented efficient outcomes on pancreatic leakage, and this indicated the promising feasibility of the bioadhesive for clinical trials and translations.
研究领域:
生物医学工程
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材料科学
·
外科手术
·
药理学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Chae Hwa Kim,Yuseok Kim,Sandeep Karna,Sung Mook Yoo,Ju Han Lee,Yun Ju Kim,Jun Hyuk Lee,Won-Min Jo,Suk-Hee Park,Tae Hee Kim
Artificial vascular grafts, as blood vessel substitutes, are a prime challenge in tissue engineering and biomaterial research. An ideal artificial graft must have physiological and mechanical properties similar to those of a natural blood vessel, and hemocompatibility on its surface. We designed and fabricated artificial grafts by applying 3D printing and templated technology, which is endowed with morphologically patient-specific vascular reconstruction. To optimize mechanical properties, the graft wall was engineered with a controllable hybrid porous structure through a multilayer combination of porous and nonporous coatings, thereby achieving biomimetic mechanical flexibility with reduced stiffness. Further, we successfully synthesized Dopamine-conjugated heparin (Hep-DA) utilizing carbodiimide chemistry, and coated it on a 3D porous graft to improve both surface adhesion and anticoagulant ability. The Hep-DA-coated 3D graft did not show significant cytotoxic effects with a long-term sustained heparin release. We performed a preclinical study in swine using the developed graft along with commercially available graft ePTFE and Dacron as a reference. They were implanted in the swine aorta for 28 days and the implanted grafts were harvested for further analysis. Histopathology study results showed the feasibility of the developed artificial vascular grafts that have less calcification, fibrosis, and collagen deposition than commercially available grafts.
研究领域:
组织工程
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生物材料科学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2024
·Vol. 29
·期 4
·132
·
IF 3.3
Wentao Lin,Yong Xia,Anqi He,Shuang Chen,Jie Zhang
Background: The incidence of melanoma brain metastasis (MBM) is high and significantly compromises patient survival and quality of life. Effective treatment of MBM is made difficult by the blood-brain barrier (BBB), since it restricts the entry of drugs into the brain. Certain anti-psychotic drugs able to cross the BBB have demonstrated efficacy in suppressing brain metastasis in preclinical studies. However, the activity of zuclopenthixol against MBM is not yet clear. Methods: Cell viability assays were employed to investigate the potential of zuclopenthixol in the treatment of MBM. Subsequently, the mechanism of action was investigated by RNA-sequencing (RNAseq), flow cytometry-based cell cycle and apoptosis assays, protein expression analysis, and autophagy flux detection. Additionally, the efficacy of zuclopenthixol against tumor growth was investigated in vivo, including MBM models. Results: Zuclopenthixol inhibited the proliferation of various melanoma cell lines at minimal doses by causing cell cycle arrest in the G0/G1 phase and mitochondrial-mediated intrinsic apoptosis. Zuclopenthixol also induced cytoprotective autophagy, and inhibition of autophagy enhanced the anti-melanoma effects of zuclopenthixol. Furthermore, zuclopenthixol inhibited the growth of human melanoma tumors in nude mice, as well as the growth of intracranial metastases in a mouse model of MBM. Conclusions: These results demonstrate that zuclopenthixol has significant potential as an effective therapeutic agent for MBM.
研究领域:
肿瘤学
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药理学
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神经科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Feng Zijin,Hu Zhijing,Li Lei,Yu Minquan,Zhang Yiting,Jing Peng,Xu Xiangqing,Wu Jinhui,Hu Yiqiao,Xu Xiangyang
Background: Schizophrenia is a serious psychiatric disorder that significantly affects the quality of life of patients. The objective of this study is to discover a novel antipsychotic candidate with highly antagonistic activity against both serotonin and dopamine receptors, demonstrating robust efficacy in animal models of positive, negative, and cognitive symptoms of schizophrenia.Methods: In the present study, we examined the activity of antipsychotic drug (NH300094) on 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1B, 5-HT7, H1, M1, Alpha1A, D2L, D2S, Alpha2A, D3 receptor functional assay in vitro. In addition, multiple animal models, including dizocilpine (MK-801) induced hyper-locomotion; APO induced climbing; Conditioned Avoidance Response (CAR); DOI-Induced Head Twitch; Forced swimming test; Scopolamine induced cognitive impairment model, were used to verify the antipsychotic activity of NH300094 in preclinical.Results: In vitro functional assays have indicated that NH300094 is a potent antagonist of 5-HT receptors and dopamine receptors, with higher relative antagonistic activity against 5-HT2A receptor (5-HT2A IC50 = 0.47 nM) than dopamine receptors (D2L IC50 = 1.04 nM; D2S IC50 = 11.71 nM; D3 IC50 = 31.55 nM). Preclinical in vivo pharmacological study results showed that NH300094 was effective in multiple models, which is more extensive than the clinic drug Risperidone. Furthermore, the safety window for extrapyramidal side effects of NH300094 is significantly wider than that of Risperidone (For NH300094, mice catalepsy model ED50/ Mice MK-801 model ED50 = 104.6-fold; for Risperidone, mice catalepsy model ED50/ Mice MK-801 model ED50 = 12.9-fold), which suggests a potentially better clinical safety profile for NH300094.Conclusion: NH300094 is a novel potent serotonin and dopamine receptors modulator, which has good safety profile and therapeutic potential for the treatment of schizophrenia with cognition disorders.
研究领域:
药理学
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精神病学
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神经科学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Jinwei Zhang,Meilin Sun,Fen Zhang,Tingting Xuanyuan,Xufang Liu,Danyang Yu,Wenming Liu
Microengineered cancer model is exceedingly practical in preclinical screening, while establishing a highly tumor-biomimetic pathophysiological microsystem with multi-function integration remains challenging. Here, an integrated microfluidic biomimetic tumor-on-a-chip (IMBTC) platform is established to reinforce at once the spatiotemporal control of fluid/cell samples and wide-range gradient (WRG), as well as the in vitro multi-feature reconstruction of native tumors for supporting diverse preclinical therapy evaluations. The active pneumatic manipulators enable precise cell capture and array-like organization with high positioning efficiency. The WRG generator can unprecedentedly create a wide range of chemical gradients with up to 8 orders of magnitude, affording efficient therapy screening evaluation in a single chip capable of producing hundreds of tumors with size-uniformity via coculturing under a physiological flow condition. Multiple high-biomimetic characteristics in the engineered tumors, including complex multilayer organization, various phenotypic/biochemical gradients involving proliferation, viability, metabolism, hypoxia, and molecular penetration, and heterogeneous cell and stroma compositions, are validated. The IMBTC system is applied to successively evaluate individual drug chemotherapy, combinatorial chemotherapy, and photosensitive drug-dominant photodynamic therapy, thereby identifying the effective lethal doses from wide-range antitumor concentration screenings. The verified IMBTC system offers considerable benefits for advancing the development of next-generation tumor-on-a-chip and an innovative preclinical screening paradigm.
研究领域:
生物工程
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微流控技术
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癌症研究
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药理学
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生物医学工程
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR DIVERSITY
·
2025
·
IF 3.8
Miao Wenjun,Yang Meixian,Peng Zhiping,Xia Zhu,Zhang Xiaoyang,Chen Yi,Jia Jianhua
Cyclooxygenase-2 (COX-2) plays vital roles in promoting angiogenesis, tissue invasion, and resistance to apoptosis, so it has become an attractive biomarker for imaging and therapy of cancer. Numerous radio-tracers for detection of COX-2 in vivo have been reported, but no one has been successfully applied in clinic. In this study, the radiosynthesis and evaluation of [ 18 F] 6 , containing a 1,5-diarylpyrrole structure, as a radiotracer for imaging of COX-2 is described. [ 18 F] 6 was prepared within 90 min synthesis time with radiochemical yields (RCYs) of 2–6% (n = 7, decay corrected) from [ 18 F]fluoride by a one-step 18 F-trifluoromethylation reaction. After purification by high performance liquid chromatography (HPLC), its radiochemical purity (RCP) was higher than 98%, and the molar activity was 156–210 MBq/mmol. The stability of [ 18 F] 6 was determined by incubation in saline and fetal bovine serum (FBS) in vitro, showing excellent stability in 4 h. The specific binding of [ 18 F] 6 was evaluated using MCF-7 cells (COX-2 positive cells) in vitro, where the radiotracer uptake was blocked in the presence of Celecoxib (a commonly used COX-2 inhibitor). However, no tumor accumulation of [ 18 F] 6 could be observed by micro-PET/CT studies on MCF-7 tumor-bearing mice in vivo. This may be due to the insufficient molar activity of [ 18 F] 6, or inadequate expression of COX-2 in MCF-7. In conclusion, optimizations of radiosynthesis and evaluations of specific binding in suitable model are further still needed to verify the potential of [ 18 F] 6 as a COX-2 imaging agent.
研究领域:
分子影像学
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核医学
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药物化学
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肿瘤学
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放射化学
✓ 已验证
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2025
·Vol. 10
·期 1
·1-17
·
IF 52.7
Su Minhui,Liu Yuan,Lin Hongxin,Wang Xiaoxing,Ying Danxia,Zhang Lizhuan,Yang Cai,Jiang Mengyuan,Xu Lujuan,Wang Xie,Sun Yang,Xu Haiyan,Zhang Ziwen,Wang Xiaojia,Fu Ting,Xie Sitao,He Jiaxuan,Liu Xiangsheng,Tan Weihong
Aptamers serve as unique targeting ligands, making aptamer-drug conjugates (ApDCs) an attractive strategy for targeted cancer therapy. This study performs a comprehensive evaluation from rodents to non-human primates (NHP) of a protein tyrosine kinase 7 (PTK7)-targeted ApDC (Sgc8c-M) made by conjugating the potent antimitotic agent monomethyl auristatin E (MMAE) to the classic PTK7 aptamer Sgc8c. Efficacy studies in various cancer types with PTK7 overexpression showed that Sgc8c-M effectively induces sustained tumor regression in cell line-derived and patient-derived xenografts, outperforming unconjugated MMAE, the chemotherapy drug paclitaxel, and a PTK7-targeted antibody-drug conjugate. Pharmacokinetic (PK) studies in mice revealed that Sgc8c-M leads to rapid accumulation and sustained MMAE levels in tumors, along with fast clearance from plasma and normal tissues. Further study in rats confirmed rapid clearance across most organs and revealed that over 75% of MMAE was excreted through urine and feces within 24 h. Toxicokinetic (TK) assessments indicated comparable systemic drug exposure without accumulation for repeated doses compared to single administration. Toxicity evaluations showed that the therapeutic dose with high efficacy was safe and that the toxicity resulting from extremely high doses could be reversibly controlled. Encouraged by these findings, we evaluated PK/TK profiles and safety of Sgc8c-M in cynomolgus monkeys. Similar to PK/TK profiles observed in rats, Sgc8c-M demonstrated good dose-dependent drug exposure. It was, moreover, well tolerated in monkeys with no obvious accumulation following multiple administrations. These findings highlight the potential of Sgc8c-M as an effective antitumor agent and provide useful insights for the clinical translation of emerging ApDCs.
研究领域:
肿瘤学
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药物代谢
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转化医学
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分子靶向治疗
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生物药剂学
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毒理学
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临床前药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2021
·Vol. 8
·期 8
·2003941
·
IF 16.806
Xian Sun,Xiaochuan Zhang,Xiaohong Ren,Hongyu Sun,Li Wu,Caifen Wang,Xiaohui Ye,Peter York,Zhaobing Gao,Hualiang Jiang,Jiwen Zhang,Xianzhen Yin
The effective pulmonary deposition of inhaled particulate carriers loaded with drugs is a prerequisite for therapeutic effects of drug delivery via inhalation route. Revealing the sophisticated lung scaffold and intrapulmonary distribution of particles at three-dimensional (3D), in-situ, and single-particle level remains a fundamental and critical challenge for dry powder inhalation in pre-clinical research. Here, taking advantage of the micro optical sectioning tomography system, the high-precision cross-scale visualization of entire lung anatomy is obtained. Then, co-localized lung-wide datasets of both cyto-architectures and fluorescent particles are collected at full scale with the resolution down to individual particles. The precise spatial distribution pattern reveals the region-specific distribution and structure-associated deposition of the inhalable particles in lungs, which is undetected by previous methods. Overall, this research delivers comprehensive and high-resolution 3D detection of pulmonary drug delivery vectors and provides a novel strategy to evaluate materials distribution for drug delivery.
研究领域:
药剂学
·
生物医学工程
·
肺科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2024
·
IF 8.2
Fangkun Yang,Jie Cao,Xiaoxue Jia,Hailiang Zhu,Jieli Zhou,Zhaocheng Liu,Hanbin Cui,Kai Wang
Cardiovascular diseases (CVDs) pose a serious threat to human health, with atherosclerosis being a leading cause of heart disease and stroke. Elevated cysteine (Cys) levels have been closely linked to an increased risk of cardiovascular diseases, underscoring its significance in cardiovascular health. However, current detection methods for cysteine in serum and atherosclerotic plaques present challenges in sensitivity, specificity, dynamic monitoring, and invasiveness. The development of more sensitive, specific, and noninvasive assays is needed to enable accurate monitoring of cysteine levels. This study introduces the development and characterization of Cys-NPs, a sensitive and selective tool for imaging cysteine in foam cells and atherosclerotic mice. Encapsulation of the HD-probe using DSPE-PEG to obtain Cys-NPs effectively reduced interference from glutathione (GSH), leading to successful preparation and validation of Cys-NPs’s nanoscale structure. At the same time, Cys-NPs was able to use the differences in Hcy and Cys concentrations in vivo to better assess Cys levels in vivo. In vitro and in vivo studies demonstrated Cys-NPs’s effective imaging of cysteine in foam cells and atherosclerotic mice, highlighting its potential for noninvasive assessment of cysteine levels in ischemic heart disease research and clinical practice.
研究领域:
心血管疾病
·
医学成像
·
纳米技术
·
分子生物学
·
临床前研究
✓ 已验证
DOI
PubMed
高影响因子
Oncotarget
·
2016
·
IF 5.008
Mei Peng,Qiongli Su,Qing Zeng,Le Li,Zhihong Liu,Lei Xue,Yan Cheng,Yanjun Huang,Ting Tao,Hongwei Lv,Xiaohui Li,Xiaojun Tao,Peng Guo,Alex F. Chen,Xiaoping Yang
Anticancer potential of metformin has been extensively studied. However, its anticancer clinical use remains yet to be approved since sufficient concentration on target organs could not be achieved via conventional administration. To overcome this drawback, we aim to examine the efficiency of novel intravesical treatment of metformin on syngeneic orthotopic preclinical model. Three human and one murine bladder cancer cell lines were tested in vitro for inhibitory sensitivity by MTT and cologenic assays. AMPK pathway including AKT, Erk and S6K was examined by western blot and further explored by regulating activated levels using specific inhibitors. In vivo efficacy was determined by Kaplan-Meier survival curves and measurements of body and bladder weights plus tumor biomarkers. Lactic acid and metformin levels of plasma were measured by standard procedures. The results demonstrated that metformin activated AMPK and decreased phosphorylation of Akt and Erk. Furthermore, combinations of metformin with either Akt or Erk inhibitors synergistically diminished cancer proliferation, suggesting the involvement of Akt- and Erk- related pathways. Intravesical metformin 26 and 104 mg/kg, twice per week demonstrated a rapid elimination of the implanted tumor without any evidence of toxicity. In contrast, oral treatment at a dose of 800mg/kg/d exhibited little efficacy whereas severe toxicity existed if the dosage is higher. Collectively, intravesical metformin displays potent inhibition on bladder cancer in vitro and this preclinical study reveals the profound therapeutic application of metformin with durable tolerance via intravesical administration route.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Wei Cheng,Haijing Qu,Jiaojiao Yang,Han Chen,Yuqing Pan,Zhiran Duan,Xiangdong Xue
Glioblastoma multiforme (GBM), particularly the deep-seated tumor where surgical removal is not feasible, poses great challenges for clinical treatments due to complicated biological barriers and the risk of damaging healthy brain tissue. Here, we hierarchically engineer a self-adaptive nanoplatform (SAN) that overcomes delivery barriers by dynamically adjusting its structure, surface charge, particle size, and targeting moieties to precisely distinguish between tumor and parenchyma cells. We further devise a SAN-guided intuitive and precision intervention (SGIPi) strategy which obviates the need for sophisticated facilities, skilled operations, and real-time magnetic resonance imaging (MRI) guidance required by current MRI-guided laser or ultrasound interventions. In a preclinical intracranial GBM mouse model, SGIPi-based photodynamic therapy effectively impedes GBM progression with high tumor specificity and significantly extends overall survival. Moreover, the SGIPi potentiates chemotherapy while minimizing adverse effects; it eradicates intracranial GBM lesions in 100% cases solely through Temozolomide chemotherapy. This SGIPi strategy holds potential to improve the clinical management of GBM, with the possibility of extending survival rates and even achieving complete remission, and may inspire research focus from expensive and complex hardware development to simpler, delivery-based GBM interventions.
研究领域:
肿瘤学
·
纳米医学
·
神经科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-18
·
IF 9.429
Xia Ya-Nan,Zu He,Guo Haoxiang,Jiang Tianyan,Yang Siqi,Yu Huan,Zhang Shaodian,Ding Heng,Li Xiaoyu,Wang Yangyun,Wang Yong,Zhang Leshuai W.
Albumin-biomineralized copper sulfide nanoparticles (Cu 2−x S NPs) have attracted much attention as an emerging phototheranostic agent due to their advantages of facile preparation method and high biocompatibility. However, comprehensive preclinical safety evaluation is the only way to meet its further clinical translation. We herein evaluate detailedly the safety and hepatotoxicity of bovine serum albumin-biomineralized Cu 2−x S (BSA@Cu 2−x S) NPs with two different sizes in rats. Large-sized (LNPs, 17.8 nm) and small-sized (SNPs, 2.8 nm) BSA@Cu 2−x S NPs with great near-infrared absorption and photothermal conversion efficiency are firstly obtained. Seven days after a single-dose intravenous administration, SNPs distributed throughout the body are cleared primarily through the feces, while a large amount of LNPs remained in the liver. A 14-day subacute toxicity study with a 28-day recovery period are conducted, showing long-term hepatotoxicity without recovery for LNPs but reversible toxicity for SNPs. Cellular uptake studies indicate that LNPs prefer to reside in Kupffer cells, leading to prolonged and delayed hepatotoxicity even after the cessation of NPs administration, while SNPs have much less Kupffer cell uptake. RNA-sequencing analysis for gene expression indicates that the inflammatory pathway, lipid metabolism pathway, drug metabolism-cytochrome P450 pathway, cholesterol/bile acid metabolism pathway, and copper ion transport/metabolism pathway are compromised in the liver by two sizes of BSA@Cu 2−x S NPs, while only SNPs show a complete recovery of altered gene expression after NPs discontinuation. This study demonstrates that the translational feasibility of small-sized BSA@Cu 2−x S NPs as excellent nanoagents with manageable hepatotoxicity. Graphical Abstract
研究领域:
纳米技术
·
药理学
·
毒理学
·
分子生物学
✓ 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）