CHEMICAL ENGINEERING JOURNAL
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2025
·
IF 13.2
Chaozheng Zhang,Yao Chen,Yi Zuo,Maolin Wang,Hongyu Chen,Chuanqi Wang,Yuening Cao,Yingjie Zeng,Ying Chen,Tingting Zhang,Xian Ge,Xiujun Cao,Yilan Liu,Hongbin Cheng,Yun Deng,Jun Lu
Ligand-receptor recognition-based nanodrug delivery systems incorporate stimulus-responsive functionality to proactively transport chemotherapeutics to lesional tissues and intelligently release drugs in response to stimulation, thereby augmenting drug accumulation at target sites, boosting drug bioavailability, and avoiding systemic toxicity, which reveals a promising potential in malignant tumor therapy. Herein, we designed and prepared a dual-targeted nanomedicine, FA-HA-SS-PPT, utilizing microwave-assisted quantitative conjugating of podophyllotoxin (PPT) to folic acid (FA) and hyaluronic acid (HA) carriers via short-chain PEG bearing the tumor microenvironment-sensitive disulfide bond. The FA-HA-SS-PPT nanoparticles developed by self-assembly exploited the peculiarity of specifically binding to the folate receptor (FR) and CD44 receptor, initiated targeting to translocate the drug into the tumor cells and released the PPT by self-cyclization in high intracellular GSH concentration. Furthermore, this nanomedicine demonstrated superior tumor cytotoxicity and proliferation inhibition in vitro by triggering the mitochondrial apoptotic pathway and suppressing the microtubule protein formation. Notably, quantitative disulfide bond conjugation and nanomedicine formation endowed FA-HA-SS-PPT nanoparticles with astonishing in vivo circulatory stability and tumor microenvironmental responsiveness, further reinforcing drug security and anti-tumor capability. Therefore, quantitatively conjugating drugs provide a promising safe and efficient means to treat multi-receptor overexpressing tumors with multi-targeted nanomedicines.
研究领域:
药剂学
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肿瘤学
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生物化学
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DOI
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2026
·
IF 8
Rucui Yu,Yan Zhang,Ruiying Wu,Jingwei Xu
Objective Mitochondrial dysfunction and dysregulated cell death are key drivers of diabetic kidney disease (DKD) progression. This study aimed to construct CD44-targeted chitosan (Cs) nanoparticles encapsulating ginsenoside Rg1 (CD44-Cs@Rg1) for targeted delivery, and to evaluate their ability to regulate autophagy, pyroptosis, and mitochondrial function in DKD. Methods CD44-Cs@Rg1 nanoparticles were synthesized using a covalent modification strategy. Their targeting uptake, effects on GSDMD-mediated pyroptosis, autophagic flux, and energy metabolism were systematically evaluated in renal tubular epithelial cells under high-glucose (HG) conditions and in DKD mouse models. Mitochondrial function was assessed by Western blotting, immunostaining, MitoSOX, JC-1, and ATP assays. Transcriptomic profiling and pharmacological interventions were applied to elucidate the involvement of the AMPK/mTOR signaling axis. Results CD44-Cs@Rg1 nanoparticles were efficiently internalized by renal tubular epithelial cells, significantly reducing pyroptosis while restoring autophagic flux through AMPK activation and mTOR inhibition. These effects improved mitochondrial membrane potential, reduced reactive oxygen species accumulation, and enhanced ATP production. In vivo , CD44-Cs@Rg1 treatment markedly ameliorated renal dysfunction and histopathological injury in DKD mice. Transcriptomic and protein-level analyses consistently revealed enrichment of pathways related to AMPK signaling, autophagy, and energy metabolism. Conclusion CD44-targeted Cs nanoparticles enable precise delivery of ginsenoside Rg1 to renal tubular cells in DKD, restoring mitochondrial homeostasis and regulating autophagy–pyroptosis balance via the AMPK/mTOR axis. This nanotherapeutic platform demonstrates strong translational potential for DKD treatment.
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Penglei Zhang,Junjie Tang,Lili Cheng,Yifan Xue,Jiahuan Yang,Zhongsheng Sun,Jie Liu
Psoriasis is a chronic inflammatory skin disorder characterized by immune dysregulation and cutaneous symptoms. Methotrexate (MTX), efficacious in psoriasis, suffers from limited transdermal permeability due to its hydrophilic nature. Liposomal nanomedicine, which offers increased bioavailability and targeted delivery with minimized systemic effects, is a promising approach. The application of hyaluronic acid (HA) as a penetration enhancer and modifier leverages its binding to the upregulated CD44 receptor in psoriasis, enhancing the efficacy of liposomes. In this study, we synthesized HA-modified liposomes by conjugating HA with distearoyl phosphatidyl ethanolamine-poly (ethylene glycol) (DSPE-PEG) and encapsulated methotrexate for targeted treatment of psoriasis. The research entailed the meticulous preparation and physicochemical characterization of these HA-modified liposomes, followed by in vitro transdermal delivery assays, cellular uptake studies, and the development of a psoriasis animal model to rigorously assess therapeutic efficacy. Our findings underscore the significant improvement in methotrexate's transdermal penetration and retention within psoriatic lesions afforded by the HA-modified liposomes, indicating a novel and efficacious therapeutic approach for the management of dermatological disorders.
研究领域:
药学
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纳米技术
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皮肤科
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2021
·Vol. 16
·期 5
·055001
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IF 3.715
Junting Tao,Shixuan Feng,Bing Liu,Jiaqi Pan,Chaorong Li,Yingying Zheng
Accurate distinguish of cancer cells through fluorescence plays an important role in cancer diagnosis. Here we synthesized a blue fluorescent nitrogen-doped graphene quantum dots (N-GQDs) from citric acid and diethylamine via one-step hydrothermal synthesis method which was simple and quick to avoid by-products, and highlighted the binding sites to achieve precise combination. Due to the nitrogen element doping, amide II bond was amply obtained and abundant binding sites were provided for hyaluronic acid (HA) conjugation. N-GQDs solution with different pH value was then conjugated to HA via an amide bond for the recognition of human breast cancer cells (MCF-7 cells), and the formation of amide bond was more favorable under alkaline conditions. HA conjugated N-GQDs (HA-N-GQDs) were combined with CD44 which was over expressed on the surface of MCF-7 cells, resulting in MCF-7 cells performing stronger fluorescence. HA-N-GQDs showed high fluorescence, low toxicity, and good cytocompatibility, which held it play a role in fluorescence imaging for accurate identification of cancer cells.
研究领域:
癌症诊断
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材料科学
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生物医学工程
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纳米技术
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-14
·
IF 10.2
Yang Wen,Wang Ning,Yang Jin,Liu Chao,Ma Shuang,Wang Xiye,Li Wenzhen,Shen Meiling,Wu Qinjie,Gong Changyang
Background Photothermal therapy (PTT) is taken as a promising strategy for cancer therapy, however, its applicability is hampered by cellular thermoresistance of heat shock response and insufficient accumulation of photothermal transduction agents in the tumor region. In consideration of those limitations, a multifunctional “Golden Cicada” nanoplatform (MGCN) with efficient gene delivery ability and excellent photothermal effects is constructed, overcoming the thermoresistance of tumor cells and improving the accumulation of indocyanine green (ICG). Results Down-regulation of heat shock protein 70 (HSP70) makes tumor cells more susceptible to PTT, and a better therapeutic effect is achieved through such cascade augmented synergistic effects. MGCN has attractive features with prolonged circulation in blood, dual-targeting capability of CD44 and sialic acid (SA) receptors, and agile responsiveness of enzyme achieving size and charge double-variable transformation. It proves that, on the one hand, MGCN performs excellent capability for HSP70-shRNA delivery, resulting in breaking the cellular thermoresistance mechanism, on the other hand, ICG enriches in tumor site specifically and possesses a great thermal property to promoted PTT. Conclusions In short, MGCN breaks the protective mechanism of cellular heat stress response by downregulating the expression of HSP70 proteins and significantly augments synergistic effects of photothermal/gene therapy via cascade augmented synergistic effects.
研究领域:
癌症治疗
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纳米技术
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分子生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
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2024
·Vol. 16
·期 10
·1327
·
IF 4.9
Huiping Zhang,Liang Li,Wei Li,Hongxia Yin,Huiyun Wang,Xue Ke
Background:CPT is a pentacyclic monoterpene alkaloid with a wide spectrum of antitumor activity. Its clinical application is restricted due to poor water solubility, instability, and high toxicity. We developed a new kind of multifunctional micelles to improve its solubility, reduce the side effecs, and obtain enhanced antitumor effects.Methods:We constructed HA-CPT nano-self-assembly prodrug micelles, which combined the advantages of pH-sensitivity, redox-sensitivity, and active targeting ability to CD44 receptor-overexpressing cancer cells. To synthesize dual sensitive HA-CPT conjugates, CPT was conjugated with HA by pH-sensitive histidine (His) and redox-sensitive 3,3′-dithiodipropionic acid (DTPA). In vitro, we studied the cellular uptake and antitumor effect for tumor cell lines. In vivo, we explored the bio-distribution and antitumor effects of the micelles in HCT 116 tumor bearing nude mice.Results:The dual-sensitive and active targeting HA-His-ss-CPT micelles was proved to be highly efficient in CPT delivery by the in vitro cellular uptake study. The HA-His-ss-CPT micelles escaped from endosomes of tumor cells within 4 h after cellular uptake due to the proton sponge effect of the conjugating His and then quickly released CPT in the cytosol by glutathione (GSH). In mice, HA-His-ss-CPT micelles displayed efficient tumor accumulation and conspicuous inhibition of tumor growth.Conclusions:The novel, dual-sensitive, active targeting nano-prodrug micelles exhibited high efficiency in drug delivery and cancer therapy. This “all in one” drug delivery system can be realized in an ingenious structure and avoid intricate synthesis. This construction strategy can illume the design of nanocarriers responding to endogenous stimuli in tumors.
研究领域:
药学
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纳米技术
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癌症治疗
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Zhiwei Wen,Shuiling Qin,Huajie Huang,Xingle Xia,Wei Zhang,Wei Wu
Anthracyclines belong to a class of anti-tumor antibiotics, and their severe cardiotoxicity significantly limits their clinical use. Exosomes play key roles in intercellular communication, characterized by high biocompatibility and specific tissue and organ homing effects. In this study, doxorubicin, an anthracycline anticancer drug widely used in clinical chemotherapy, was selected as a model drug. To address the significant cardiotoxicity associated with doxorubicin, tumor exosomes are utilized as drug carriers. The homing effect of autologous exosomes enhances drug uptake by tumor cells and reduces cardiotoxicity. To enhance the stability of exosomes, improve therapeutic effectiveness, and reduce toxic side effects, chitosan was utilized to modify the surface of exosomes. Chitosan has a specific anti-tumor effect because it can target the CD44 receptor of tumor stem cells and interact with tumor cells through charge adsorption. Through in vitro cell experiments, in vivo pharmacokinetic experiments, and an in situ ectopic nude mouse tumor model, the study demonstrated that chitosan-modified tumor exosomes significantly alleviated the severe cardiotoxicity of doxorubicin, while also showing remarkable anti-tumor efficacy. This study introduces a novel approach to reduce the adverse side effects of anthracycline chemotherapeutic drugs and presents a highly promising nanocarrier delivery system.
研究领域:
药理学
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肿瘤学
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纳米技术
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
RSC Advances
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2016
·Vol. 6
·期 46
·39896-39902
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IF 3.289
Lipeng Qiu,Mengqin Zhu,Yan Huang,Kai Gong,Jinghua Chen
Plenty of hyaluronic acid (HA) drug delivery systems have been developed to target cancer cells. Carboxyl of HA is the active group for targeting CD44 receptor, which is overexpressed in several different types of cancer cells. To verify whether the number of carboxyl is the main factor in cellular uptake, hyaluronic acid–octadecylamine (HM) conjugates with 12–51% degrees of substitution (DS) were synthesized. Moreover, a series of doxorubicin (DOX)-loaded HM micelles (DOX/HM) were prepared and characterized. With the increase of DS, the sizes of DOX/HM decreased obviously. The micelles had good fetal bovine serum stability and presented a controlled-release manner. In vitro cytotoxicity tests showed that all the blank micelles were nontoxic against Michigan Cancer Foundation-7 (MCF-7) cells (overexpressed CD44 receptors), whereas DOX/HM micelles with DS of 23% (DOX/HM23) exhibited optimal enhanced anticancer activity. Cellular uptake experiments showed that compared with the other micelles, DOX/HM23 had the appropriate DS and particle size, which led to remarkably efficient internalization to achieve the highest intracellular drug concentration. These results indicate that both the carboxyl groups and particle size play important roles in the cellular uptake of HA-based micelles.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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产品关联
DOI
高影响因子
Antibiotics-Basel
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2025
·Vol. 14
·期 8
·824
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IF 4.6
Pu Guo,Xuwen Liu,Xiaoyi Li,Awais Ihsan,Zhongyuan Wu,Shulin Fu,Chun Ye,Yinsheng Qiu,Xu Wang,Qirong Lu,Yu Liu
Background:Glaesserella parasuis(GPS) is a conditional pathogen that colonizes the upper respiratory tract in pigs and causes Glässer’s disease, resulting in high morbidity and mortality in piglets. GPS infection increases the vascular endothelial permeability, but the mechanism has not been fully elucidated. Luteolin (Lut) is a naturally occurring flavonoid found in plants such as vegetables, herbs, and fruits, but its potential to treat the increased vascular endothelial permeability caused by GPS infection has not been evaluated.Results:This study revealed that GPS infection induces increased vascular endothelial permeability in porcine iliac artery endothelial cells (PIECs) by increasing the gene expressions of tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-8, and IL-1β, and by regulating F-actin cytoskeleton reorganization. Mechanistically, GPS infection or Cluster of differentiation 44 (CD44) overexpression significantly increased the expressions of vascular-endothelial-permeability-related proteins (CD44; vascular endothelial growth factor (VEGFA); matrixmetalloProteinase-3 (MMP-3); MMP-9; and SRC proto-oncogene, non-receptor tyrosine kinase (c-Src)) and increased the vascular endothelial permeability; these changes were alleviated by a Lut treatment or CD44 silencing in the PIECs.Conclusions:This study comprehensively illustrates the potential targets and molecular mechanism of Lut in alleviating the GPS-induced increase in vascular endothelial permeability. The CD44 pathway and Lut may be an effective target and antibiotic alternative, respectively, to prevent the increased vascular endothelial permeability caused by GPS.
研究领域:
兽医学
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微生物学
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药理学
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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
Frontiers in Bioengineering and Biotechnology
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2023
·
IF 5.7
Liu Zhanbiao,Chen Xuejun,Jin Qian,Li Min,Zhu Siqing,Zhang Yi,Zhi Defu,Zhao Yinan,Li Liqin,Zhang Shubiao
Although many carriers for the delivery of chemotherapeutic drugs have been investigated, the disadvantages of passive targeting and uncontrolled drug release limit their utility. Herein, hyaluronic acid (HA) was hydrophobically modified to serve as a carrier for binding to cluster determinant 44 (CD44) overexpressed on tumor cell surfaces. Specifically, after deacetylation, HA was grafted to dodecylamine or tetradecylamine to afford amphiphilic zwitterionic polymer micelles, designated dHAD and dHAT, respectively, for the delivery of paclitaxel (PTX). The micelles were negatively charged at pH 7.4 and positively charged at pH 5.6, and this pH sensitivity facilitated PTX release under acidic conditions. The cell uptake efficiencies of the dHAD-PTX and dHAT-PTX micelles by MCF-7 cells after 4 h of incubation were 96.9% and 95.4%, respectively, and their affinities for CD44 were twice that of HA. Furthermore, the micelles markedly inhibited tumor growth both in vitro and in vivo, with IC50 values of 1.943 μg/mL for dHAD-PTX and 1.874 μg/mL for dHAT-PTX for MCF-7 cells; the tumor inhibition rate of dHAD-PTX (92.96%) was higher than that of dHAT-PTX (78.65%). Importantly, dHAD and dHAT micelles showed negligible systemic toxicity. Our findings suggest that these micelles are promising delivery vehicles for antitumor drugs.
研究领域:
药学
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癌症研究
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Weibin Jia,Runrun Li,Fengjuan Zou,Min Li,Hongjuan Weng,Qianqian Shen,Guozhen Qi,Ruipiao Zhou,Yikang Shi,Guofeng Gu,Fengshan Wang,Zonggang Chen
The major drawback of conventional chemotherapeutic treatment is the non-specificity or inability to ascertain and target cancerous cells directly. In this study, an active targeting strategy that is poised to carry the anticancer agents to the desired sites for therapeutic action while avoiding toxicity to normal organs is provided. The active targeting of delivery vehicles is achieved by ligand-receptor interactions, in particular the specific binding between hyaluronic acid oligosaccharides (oHAs) and CD44 receptors. This study first prepares oHAs by the size-exclusion chromatography and utilizes them to decorate chitosan (CTS) as basic materials (oHAs-CTS) for drug delivery, then fabricates oHAs-CTS into micro/nanoscale carriers to encapsulate agents for cancer chemotherapy. The oHAs-CTS micro/nanocarriers exhibit high drug encapsulation efficiency (58–87%), and the drug releases present a sustained behavior. Notably, oHAs-CTS delivery vehicles display an enhanced active targeting toward cancers and alleviate the cytotoxic effects on normal cells. Additionally, in vivo results show that drug-laden oHAs-CTS nanocarriers demonstrate a significant inhibitory effect on 4 T1 tumors without any toxicity to the major organs. Taken together, the findings highlight the potential of oHAs-CTS micro/nanospheres as delivery vehicles with enhanced active targeted capability toward cancers and minimized adverse effects of chemotherapeutic agents for cancer treatment.
研究领域:
药学
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纳米技术
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癌症研究
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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
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2020
·
IF 4.845
Kaipei Luo,Shaoping Yin,Ruixia Zhang,Hua Yu,Guangji Wang,Juan Li
The efficient delivery of chemotherapeutic drugs to the tumor tissues unavoidably encounters numerous obstacles, such as poor tumor targeting capability, slow intracellular drug release and massive accumulation in the liver. In this study, by self-assembling methoxy poly (ethylene glycol)-poly (lactide) block copolymer (mPEG-PLA) and hyaluronic acid-paclitaxel conjugate (HA-PTX), the composite nanoparticles (mPPHP NPs) were fabricated for efficient therapy of cancer. mPPHP NPs formed self-assembled nanoparticles (116 nm in diameter) with a narrow size distribution; and showed a rapid release of PTX in the presence of hyaluronidase and esterase . mPPHP NPs exhibited enhanced internalization by cells via CD44 receptors and selected cytotoxicity against A549 cells in vitro . More importantly, compared with other PTX formulations, mPPHP NPs were demonstrated to present the reduced liver accumulation, excellent tumor-targeting ability and superior antitumor efficacy in vivo , with a TIR of 75.9%. The multifunctional composite nanoparticles could be developed as a promising nano-carrier for improved therapeutic efficacy.
研究领域:
肿瘤学
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纳米医学
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药剂学
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分子靶向治疗
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药物递送系统
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转化医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）