Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Fangfei Li,Zhaoxin Zhang,Qinyan Shi,Rubing Wang,Ming Ji,Xiaoguang Chen,Yong Li,Yunbao Liu,Shishan Yu
Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13a S )-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10- b ] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD + ) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi–pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.
研究领域:
肿瘤学
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药理学
·
分子生物学
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DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Weicheng Chen,Jiaxu Shi,Dachuan Liu,Kai Lu,Jianlong Fu,Jingxi Xu,Huan Wang,Zhiliang Guo,Li Dong,Di Li,Xin Li,Miodrag J. Lukic,Wei Xia,Song Chen,Bin Li
Repositioning and securing the cranial bone flap after craniotomy remain significant challenges in neurosurgery. Traditional fixation methods often suffer from weak mechanical strength, bioinertness, limited osteogenic capacity, and a lack of antibacterial properties, complicating clinical outcomes. Recent medical adhesives offer superior fixation but face significant limitations in cranial bone applications. In this study, we explored the application of PAH (Poly (allylamine) hydrochloride)-TPP (Tripolyphosphate) coacervate (PT) as a bone adhesive. The PT coacervate demonstrated excellent anti-swelling (anti-swelling ratio less than 1 %), self-healing, and injectable properties, as well as exceptional shape adaptability and cytocompatibility. Adhesion tests revealed its outstanding adhesion (99.06 ± 11.76 kPa for lap shear and 121.42 ± 16.73 kPa for end to end), long-term durability, and tunable adhesion strength. Furthermore, the coacervate demonstrated broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria (antibacterial rate more than 90 %), with mechanistic studies revealing promising strategies to address localized and systemic drug-resistant infections. Additionally, the coacervate's self-mineralizing properties significantly enhanced its osteogenic performance. In vivo studies confirmed its effective fixation, robust antibacterial activity, and improved osteogenesis, underscoring its suitability for cranial bone flap repositioning and fixation after craniotomy. In summary, this coacervate adhesive offers a promising therapeutic solution for addressing the challenges of cranial flap fixation in neurosurgery.
研究领域:
神经外科
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生物材料学
·
医学工程
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DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2025
·
IF 14.2
Chuanyi Liu,Wenlong Xu,Cheng Wang,Dong Ma,Zhihui Zeng,Na Wu
In industrial explosion accidents, mechanical shock waves and flame thermal radiation are the main destructive factors, posing serious threat to life and property. Current designs mainly focus on one of these factors, so it is necessary to develop protective materials against both destructive factors. TPP (Triphenyl phosphate) - SiO 2 Aerogel synergistically modified polyurea composites were developed in this work, which process excellent mechanical shock wave mitigation performance and enhanced flame retardancy. The mechanical shock wave mitigation experiments were conducted on Multi-purpose Shock Cannon (MSC), Human Tissue Equivalent Target (HTET) and full-scale human head model, which comprehensively evaluated the protective performance of polyurea composites for the human body. The flame retardancy was assessed through thermal conductivity, LOI, thermal gravimetric and small flame experiment. The combustion residue was analyzed using SEM, EDS, Raman spectroscopy, and XPS technologies, revealing flame retardant mechanism of TPP-SiO 2 Aerogel synergistically modified polyurea composites. The results showed that the TPP-SiO 2 Aerogel synergistically modified polyurea composites achieved the highest mitigation ratios of overpressure peak and acceleration peak at 13.20% and 60.87%, respectively, superior to those of fiber-enhanced polymer composites (Fiber-PE, Fiber-PA6, Fiber-ASA), single filler polyurea, wood and PLA plastic. The flame retardancy was effectively improved, with the highest LOI reaching 24.9%, far higher than that of pure polyurea (19.6%). It particularly enhanced the carbonization performance of polyurea composites during combustion, eliminating burning material dropping phenomenon. The thermal insulation performance was also elevated, with the lowest thermal conductivity reduced by 58.6% compared to pure polyurea.
研究领域:
材料科学
·
安全工程
·
燃烧学
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DOI
高影响因子
Bio-Design and Manufacturing
·
2021
·Vol. 4
·期 4
·776-789
·
IF 6.302
Fei Panyu,Ding Haibo,Duan Yu,Wang Xinyi,Hu Wei,Wu Peng,Wei Mengxiao,Peng Zhengchun,Gu Zhongze,Chen Wei
Biophysical restrictions regulate protein diffusion, nucleus deformation, and cell migration, which are all universal and important processes for cells to perform their biological functions. However, current technologies addressing these multiscale questions are extremely limited. Herein, through two-photon polymerization (TPP), we present the precise, low-cost, and multiscale microstructures (micro-fences) as a versatile investigating platform. With nanometer-scale printing resolution and multiscale scanning capacity, TPP is capable of generating micro-fences with sizes of 0.5–1000 μm. These micro-fences are utilized as biophysical restrictions to determine the fluidity of supported lipid bilayers (SLB), to investigate the restricted diffusion of Src family kinase protein Lck on SLB, and also to reveal the mechanical bending of cell nucleus and T cell climbing ability. Taken together, the proposed versatile and low-cost micro-fences have great potential in probing the restricted dynamics of molecules, organelles, and cells to understand the basics of physical biology. Graphic abstract
研究领域:
细胞生物学
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生物物理学
·
微制造
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DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
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2019
·Vol. 44
·期 1
·162-170
·
IF 3.069
Dawei Jiang,Tao Yue,Guichen Wang,Chaochao Wang,Chao Chen,Hongliang Cao,Yun Gao
Due to biological safety and negligible toxicity, nitric oxide (NO) therapy has gained increasing interest in the field of cancer therapy during the past few years. However, individual NO cancer therapy normally exhibited limited therapeutic efficiency. In order to acquire satisfactory therapeutic outcomes, the NO therapy is usually combined with other therapeutic treatments, mostly chemotherapy. Herein, we constructed HA-TPP@NORM nanoparticles based on the co-assembly of an NO donor (NORM) and tetraphenylporphyrin (TPP)-modified hyaluronic acid, which can efficiently generate a highly biocidal molecule of peroxynitrite (ONOO−) via the synergistic interactions of the nitric oxide (NO) therapy and photodynamic therapy (PDT) to enhance the cancer therapeutic efficiency. In addition, MTT results exhibited that without light irradiation, the HA-TPP@NORM nanoparticles have favourable biocompatibility with the cell viability above 95% at the maximum TPP concentration (20 μg mL−1). Under simultaneous irradiation with 365 nm and 650 nm light, ONOO− can be efficiently produced in cancer cells via the direct coupling reaction of the generated NO and superoxide anion radical (O2˙−), which significantly enhanced the anticancer effect, when compared with individual NO therapy or PDT therapy. Therefore, the HA-TPP@NORM nanoparticles may provide a new insight into the design of efficiently NO-related cancer therapeutic systems.
研究领域:
生物医学工程
·
癌症治疗研究
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DOI
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
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2021
·
IF 6.165
Yong Hu,Guojing Mo,Ying Wang,Juan Guo,Chao Huang
The TPP-β-cyclodextrin/chitosan (TPP-β-CD/CS) nanoparticles loading with curcumin (Cur) and vitamin C (Vc) was prepared via controllable self-assembly. The cross-linking reaction between TPP-β-CD and CS, and co-encapsulation of Cur and Vc in TPP-β-CD/CS nanoparticles were confirmed by the fourier-transform infrared (FTIR), UV–Vis (UV), X-ray diffraction (XRD), atomic force microscope (AFM), and particle size analyzer. The results of stability and antioxidant activity indicated that co-encapsulation not only enhanced the chemical stability of Cur and Vc, but also improved antioxidant properties compared with the active ingredients used alone. Release kinetic fitted by Ritger–Peppas model revealed that the release of dual active ingredients were mainly dominated by Fickian diffusion in pH 1.2, while followed non-Fickian or anomalous diffusion in pH 7.4. Furthermore, the two-dimensional UV correlation spectroscopy (2D-UV-COS) confirmed that the release rate of Cur was faster than that of Vc during co-delivery, which helps to precisely elucidate the synergistic nutraceuticals effect of each active ingredient.
研究领域:
纳米技术
·
药学
·
材料科学
·
药物递送系统
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生物医学工程
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Liqiang Wang,Xiaoyu Yuan,Qianyu Cai,Yutong Chen,Zhi Jia,Qiongmei Mai,Jie Liu,Yanan Liu
ABSTRACT Mitochondrial dysfunction in microglia has been implicated as a key pathogenesis of most neurodegenerative diseases including Alzheimer's disease (AD). Abnormal production of reactive oxygen species (ROS) and neuroinflammation caused by mitochondrial oxidative stress are important factors leading to neuronal death in AD. Herein, a "dual brake" strategy to synergistically halt mitochondrial dysfunction and neuroinflammation targeting mitochondria in microglia is proposed. To achieve this goal, (3-carboxypropyl) triphenyl-phosphonium bromide (TPP)-modified Cu 2-x Se nanozymes (Cu 2-x Se-TPP NPs) with dual enzyme-like activities was designed. Cu 2-x Se-TPP NPs with superoxide dismutase-mimetic (SOD) and catalase-mimetic (CAT) activities can effectively scavenge ROS in the mitochondria of microglia and relieve mitochondrial oxidative stress. In vivo studies demonstrated that Cu 2-x Se-TPP NPs can alleviate oxidative stress and promote neuroprotection in the hippocampus of AD model mice. In addition, Cu 2-x Se-TPP NPs can regulate the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, promote A β phagocytosis and reshape the AD inflammatory microenvironment, thus effectively attenuating AD neuropathology and rescuing cognitive deficits in AD model mice. Taken together, this strategy preventing mitochondrial damage and remodeling the inflammatory microenvironment will provide a new perspective for AD therapy.
研究领域:
神经科学
·
药理学
·
纳米技术
·
生物医学工程
·
神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Zi-Wei Jing,Yi-Yang Jia,Ning Wan,Min Luo,Meng-Lei Huan,Tai-Bin Kang,Si-Yuan Zhou,Bang-Le Zhang
The covalently modified ureido-conjugated chitosan/TPP multifunctional nanoparticles have been developed as targeted nanomedicine delivery system for eradication of Helicobacter pylori . H. pylori can specifically express the urea transport protein on its membrane to transport urea into cytoplasm for urease to produce ammonia, which protects the bacterium in the acid milieu of stomach. The clinical applicability of topical antimicrobial agent is needed to eradicate H. pylori in the infected fundal area. In this study, we designed and synthesized two ureido-conjugated chitosan derivatives UCCs-1 and UCCs-2 for preparation of multifunctional nanoparticles. The process was optimized in order to prepare UCCs/TPP nanoparticles for encapsulation of amoxicillin. The results showed that the amoxicillin-UCCs/TPP nanoparticles exhibited favorable pH-sensitive characteristics, which could procrastinate the release of amoxicillin at gastric acids and enable the drug to deliver and target to H. pylori at its survival region effectively. Compared with unmodified amoxicillin-chitosan/TPP nanoparticles, a more specific and effective H. pylori growth inhibition was observed for amoxicillin-UCCs/TPP nanoparticles. Drug uptake analysis tested by flow cytometry and confocal laser scanning microscopy verified that the uptake of FITC-UCCs-2/TPP nanoparticles was associated with urea transport protein on the membrane of H. pylori and reduced with the addition of urea as competitive transport substrate. These findings suggest that the multifunctional amoxicillin-loaded nanoparticles have great potential for effective therapy of H. pylori infection. They may also serve as pharmacologically effective nanocarriers for oral targeted delivery of other therapeutic drugs to treat H. pylori .
研究领域:
药学
·
纳米技术
·
微生物学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2023
·
IF 6.7
Zhang Shengqing,Cai Jinhong,Yao Yi,Huang Lanli,Zheng Li,Zhao Jinmin
Excessive reactive oxygen species (ROS)-induced mitochondrial damage has impact on osteoarthritis (OA). Nanozyme mimics as natural enzyme alternatives to scavenge excessive ROS has offered a promising strategy for OA therapy. Herein, we reported a novel mitochondrial-targeting Mn3O4/UIO-TPP nanozyme using metal-organic frameworks (MOFs) with loaded Mn3O4 as the enzyme-like active core combining mitochondria-targeting triphenylphosphine (TPP) groups to serve as ROS scavengers for therapy of OA. With sequential catalysis of superoxide dismutase (SOD)-like, catalase (CAT)-like, and hydroxyl radical (·OH) scavenging potentials, the nanozyme can target mitochondria by crossing subcellular barriers to effectively eliminate ROS to restore mitochondrial function and inhibit inflammation and chondrocyte apoptosis. It also has favorable biocompatibility and biosafety. Based on anterior cruciate ligament transection (ACLT)-induced OA joint models, this mitochondrial-targeting nanozyme effectively mitigated the inflammatory response with the Pelletier score reduction of 49.9% after 8-week therapy. This study offers a prospective approach to the design of nanomedicines for ROS-related diseases.
研究领域:
纳米医学
·
骨科
·
生物化学
·
药学
·
生物技术
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Yong Mei,Xiaohua Qin,Zhenyu Yang,Shiyao Song,Xiaoting Liu,Chong Wu,Jieying Qian,Xiaowan Huang,Yunjiao Zhang,Weiling He
KRAS-TP53 co-mutation is strongly associated with poor prognosis and high malignancy in gastrointestinal cancers. Therefore, a novel approach to oncotherapy may lie in combination therapy targeting both KRAS and TP53 . Herein, we present a novel self-assembled nanoparticle (HA-TPP/A) that are functionalized nano-carrier hyaluronic acid (HA)-TPP conjugate (HA-TPP) to degrade mutant p53 proteins (mutp53) and co-deliver AMG510 for treating KRAS-TP53 co-alteration of gastrointestinal cancers by inhibiting the mutant KRAS and mutp53 signaling pathways. The HA-TPP/A nanoparticles led to ubiquitination-dependent proteasomal degradation of mutp53 by targeting damage to mitochondria. Furthermore, these nanoparticles abrogated the gain-of-function (GOF) phenotypes of mutp53 and increased sensitivity to AMG510-induced cell killing, thereby reducing cell proliferation and migration in gastrointestinal cancer with KRAS-TP53 co-mutation. The co-loaded HA-TPP/A nanoparticles demonstrated remarkable therapeutic efficacy in a tumor-bearing mouse model, particularly in KRAS-TP53 double mutant expressing cancer cells, compared with single drug and combined free drug groups. Notably, HA-TPP/A is the first reported nanoparticle with an ability to co-target KRAS-TP53 , providing a promising approach for therapy in highly malignant gastrointestinal tumors and potentially expanding clinical indications for AMG510 targeted therapies in gastrointestinal tumors.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 41
·25694-25701
·
IF 3.108
Xiaoju Shi,Guoyue Lv,Xiaodong Sun,Dianbo Cao,Guangyi Wang,Yulei Chang
Recently, several targeted drug delivery systems have shown promising antitumor activity towards different types of cancer. However, targeting the tumor microenvironment, cellular surface and/or only one organelle may not achieve the expected therapeutic effects. Herein, a targeted drug delivery with stepwise targeting and image-guided strategy was obtained for enhancing antitumor therapy and overcoming various problems caused by the random drug distribution of traditional medicine. In this design, a multifunctional nanoplatform, TPGS/PPG2L@IONPs@DOX/TPP–DOX, based on poly(ethylene glycol)-poly(ε-caprolactone)-poly(amidoamine)-lactose acid (mPEG-PCL-G2.0 PAMAM-LA, PPG2L) copolymer and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS), as a co-carrier, incorporates iron oxide nanoparticles (IONPs) as imaging agents and loads a DOX/triphenylphosphonium (TPP)–DOX drug for chemotherapy. In this nanoplatform micelle, the LA as targeting moieties to hepatocarcinoma cells is the first targeting step. After the drug is released from the hybrid micelles, the incorporated DOX and TPP–DOX target delivery to nuclei and mitochondria for the next targeting step. Furthermore, with the help of MRI contrast agents of IONPs, the distribution of hybrid micelles was monitored. As a result, the hybrid micelles demonstrated enhanced antitumor cell activity in both HepG2 and HepG2/DOX cells. The results indicated that the multifunctional hybrid micelles showed great potential in enhancing antitumor activity under image-guided and stepwise targeted chemotherapy.
研究领域:
药学
·
癌症研究
·
纳米技术
·
医学影像
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产品关联
DOI
高影响因子
Materials Today Bio
·
2026
·
IF 11
Jinguo Xu,Yujun Li,Jiafeng Xu,Ruobing He,Fengchi Jiang,Jiaxue Lu,Tao Xu,Jie Wang,Chengxin Zhang
Acute kidney injury (AKI) is a critical clinical syndrome closely associated with mitochondrial dysfunction. Its etiology encompasses both intrinsic renal factors and extrarenal factors, such as cardiac complications following heart surgery. AKI remains a formidable therapeutic challenge due to the absence of strategies capable of precisely targeting and reversing mitochondrial dysfunction, a key pathological driver. To address this, we developed a renal-targeted mitochondrial autophagy inducer, tFNA-TPP, by covalently linking tetrahedral framework nucleic acid (tFNA) with triphenylphosphine (TPP) using click chemistry. This nanocomposite demonstrates a 91.6% efficiency in targeting the kidneys and functions as an integrated system for ROS scavenging and mitophagy activation. The tFNA component promotes renal accumulation and neutralizes reactive oxygen species, while the TPP moiety ensures precise delivery to damaged mitochondria, enhancing organelle-specific autophagy. In AKI models induced by both cisplatin and ischemia-reperfusion, tFNA-TPP effectively enhanced mitophagic flux, as evidenced by a 4.2-fold increase in the LC3-II/LC3-I ratio and a reduction in p62 expression, facilitating the clearance of impaired mitochondria and the restoration of renal function. By concurrently addressing oxidative stress and mitochondrial integrity, our study establishes a versatile platform for organelle-level therapy, offering a transformative approach for treating AKI and other conditions driven by mitochondrial dysregulation.
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DOI
PubMed
高影响因子
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