Regenerative Biomaterials
·
2022
·
IF 5.763
Wu Hao,Gao Yuan,Ma Jia,Hu Maosong,Xia Jing,Bao Shuting,Liu Yuxi,Feng Kai
Acute myelogenous leukemia (AML) remains a serious fatal disease for the patients and effective treatment strategies are urgently needed. Based on the characteristics of the AML, we developed the CD44 and bone targeting liposomes delivery system decorated with the redox-cleavable polymer. First, ALN-HA was obtained by amination between alendronate (ALN) and hyaluronic acid (HA), and cholesterol (Chol) was coupled by a disulfide linker (-SS-) with biological reducibility to obtain the goal polymer, ALN-HA-SS-Chol, decorated the liposomes loaded with the Cytarabine (AraC). ALN-HA-SS-AraC-Lip exhibited a spherical morphology with the diameter of 117.5 nm and expanded at the environment of 10 mM dithiothreitol. Besides, compared with other groups, ALN-HA-SS-AraC-Lip showed benign hydroxyapatite affinity in vitro and bone targeting in C57/BL6 mice, also, ALN-HA-SS-AraC-Lip exhibited encouraging antitumor which significantly reduced the white blood cell amount in bone marrow and blood smear caused by AML model, besides, the dual targeting liposomes also prolong the survival time of mice. In conclusion, the bone and CD44 dual targeting liposomes with redox sensitivity could target to the leukemia stem cells regions and then uptake by the tumor cells, which would be a valuable target for the treatment of the AML.
研究领域:
药理学
·
肿瘤学
·
纳米技术
·
血液学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF LIPOSOME RESEARCH
·
2023
·
IF 4.4
Ju Huang,Jian Chen
To develop a PEGylated and CD44-targeted liposomes, enabled by surface coating with hyaluronic acid (HA) via amide bond to improve the efficacy of imatinib mesylate (IM), for tumor-targeted cytoplasmic drug delivery. HA was covalently grafted on DSPE-PEG2000-NH2 polymer. HA-modified or unmodified PEGylated liposomes were prepared with ethanol injection method, and the stability, drug release, and cytotoxicity of these liposomes were studied. Meanwhile, intracellular drug delivery efficiency, antitumor efficacy, and pharmacokinetics were also investigated. Ex vivo fluorescence biodistribution was also detected by small animal imaging. In addition, endocytosis mechanism was also explored HA-coated PEGylated liposomes (137.5 nm ± 10.24) had a negative zeta potential (−29.3 mV ± 5.44) and high drug loading (27.8%, w/w). The liposomes were stable with cumulative drug leakage (<60%) under physiological conditions. Blank liposomes were nontoxic to Gist882 cells, and IM-loaded liposomes had higher cytotoxicity to Gist882 cells. HA-modified PEGylated liposomes were internalized more effectively than non-HA coating via CD44-mediated endocytosis. Besides, the cellular uptake of HA-modified liposomes also partly depends on caveolin-medicated endocytosis and micropinocytosis. In rats, both liposomes produced a prolonged half-life of IM (HA/Lp/IM: 14.97h; Lp/IM: 11.15h) by 3- to 4.5-folds compared with the IM solution (3.61h). HA-decorated PEGylated liposomes encapsulated IM exhibited strong inhibitory effect on tumor growth in Gist882 cell-bearing nude mice and formation of 2D/3D tumor spheroids. The Ki67 immunohistochemistry result was consistent with the above results. IM-loaded PEGylated liposomes modified with HA exerted the excellent anti-tumor effect on tumor-bearing mice and more drugs accumulated into the tumor site.
研究领域:
药学
·
肿瘤学
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药理学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2019
·
IF 5.57
Chao Teng,Zhuodong Chai,Zhongyue Yuan,Lianjie Ren,Chenshi Lin,Zhen Yan,Wei He,Chao Qin,Lei Yang,Xiaopeng Han,Lifang Yin
PEG coating was regarded as one effective method to improve the tumor-targeting efficiency of hyaluronic acid-based nanoparticles (HBN). However, the research of interaction between PEG coating and different receptors such as stabilin-2 and CD44 was limited. Herein, we synthesized a series of PEGylated hyaluronic acid with Curcumin (PHCs) to evaluate the role of PEG coating density in the interaction between HA and its receptors, which influenced tissues targeting activity, pharmacokinetic profiles and therapeutic efficacy of HBN. Compared with other counterparts, PHC HBN with about 5% PEG coating density preferably accumulated in the tumor mass, rather than in the liver, and hold desirable anti-cancer effect. These results indicated that to obtain optimized anticancer effect of HBN, the cellular uptake efficiency between different types of the cells should be carefully balanced by different PEG densities.
研究领域:
药剂学
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肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Congjian He,Jiahui Zhou,Xixi Wu,Yujin Zhou,Siya Wang,Bo Liu,Ting Luo,Ying Chen,Jia Yuan,Di Wang,Chen Zhang,Jinfeng Shi
Low concentrations or limited residence times in tumor tissues, making celastrol (Cel) difficult to exert significant therapeutic effects. Thus, we developed Zein/hyaluronic acid core-shell nanoparticles (Cel/Zein@HA NPs) for active targeted delivery of Cel via CD44 receptor over-expression on cancer cells, which may strengthen the therapeutic efficacy of Cel and improve delivery targeting. Cel-loaded Zein nanoparticles (core), are elegantly enveloped by a hydrophilic HA coating that forms the shell, resulting in significantly improved encapsulation efficiency and ensured good stability. The cellular uptake of Cel/Zein@HA NPs in HepG2 cells was 1.57-fold higher than nontargeting Cel/Zein NPs. Near-infrared fluorescence imaging confirmed the accumulation of Cel/Zein@HA NPs in H22 liver cancer tumors in mice, resulting in effective antitumor effects and good biosafety. Besides, in vitro and in vivo experiments showed that compared with Cel/Zein NPs, Cel/Zein@HA NPs had more efficient inhibitory effect on tumor proliferation and lower systemic toxicity. Further studies revealed that Cel/Zein@HA NPs induced apoptosis in hepatocellular carcinoma cells by modulating Bax and Bcl-2 expression, while also inhibiting tumor angiogenesis by decreasing CD31 and VEGF levels. Overall, this study presents a promising strategy for enhancing targeted liver cancer therapy through the utilization of biopolymer nanoparticle-based nano-pharmaceuticals that facilitate CD44-mediated cellular uptake.
研究领域:
药学
·
纳米技术
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癌症研究
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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
NEW JOURNAL OF CHEMISTRY
·
2019
·Vol. 43
·期 31
·12275-12282
·
IF 3.069
Beibei Lu,Yuanbin Li,Zhenyuan Wang,Binshen Wang,Xi Pan,Weiwei Zhao,Xing Ma,Jiaheng Zhang
The therapeutic efficacy of anticancer drug delivery systems is severely truncated by their low tumor target ability and inefficient drug release at the target site. Herein, we report the design and synthesis of a novel dual-responsive hyaluronic acid-grafted poly(ionic liquid) block copolymer that was able to self-assemble into spherical nanoparticles in water. Then, the doxorubicin-loaded block copolymer produced particles of 100 nm in size as examined using transmission electron microscopy and dynamic light scattering. The hyaluronic acid-grafted block copolymer micelles were efficiently taken up by CD44-overexpressing cancer cells as indicated by the cell counting kit-8 assays, confocal laser scanning microscopy, and flow cytometry experiments. Therefore, the as-prepared block copolymer micelles had good biocompatibility, low toxicity, and high selectivity, thus offering promise for the treatment of various CD44-overexpressing cancers.
研究领域:
药学
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材料科学
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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
✓ 已验证
产品关联
DOI
高影响因子
GIANT
·
2025
·
IF 4.9
Yanrong Shuai,Xiaojuan Miao,Yan Wang,Chaozheng Zhang,Yu Liu,Yuening Cao,Tingting Zhang,Jun Lu,Yilan Liu
Conventional DNA double-strand breaks (DSBs)-inducing chemotherapeutics for acute myeloid leukemia (AML) are often limited by poor solubility, non-selectivity, and drug resistance stemming from robust tumor DNA repair mechanisms. Here, we report a glutathione (GSH)-responsive, dual-targeting nano-prodrug, designated HA-FA@Etp-Olp, for efficient AML cell eradication. The HA-FA@Etp-Olp system was constructed through the conjugation of the PARP inhibitor Olaparib (Olp) with Etoposide (Etp) via a disulfide linkage, forming an Etp-Olp heterodimeric prodrug. This hydrophobic conjugate was encapsulated within a polymeric carrier composed of poly (ethylene glycol)-modified hyaluronic acid (HA) functionalized with folic acid (FA), self-assembling into well-refined nanoparticles. Exhibiting excellent circulatory stability, HA-FA@Etp-Olp achieved efficient accumulation within AML cells leveraging CD44/FR dual-receptor-mediated active targeting, followed by GSH-triggered disassembly and specific drug release in response to elevated intracellular GSH levels. Furthermore, HA-FA@Etp-Olp elicited a synergistic cytotoxic effect against AML through a dual-pronged mechanism: "DNA damage-repair blockade" cascade and significant augmentation of mitochondrial oxidative stress, effectively inducing apoptotic cell death. This strategy provides a promising targeted nanotherapeutic approach with enhanced efficacy and reduced systemic toxicity, demonstrating significant potential for the precise treatment of AML.
研究领域:
肿瘤学
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纳米医学
·
药剂学
·
分子生物学
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转化医学
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血液病学
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药物递送
✓ 已验证
DOI
高影响因子
LABORATORY INVESTIGATION
·
2018
·Vol. 98
·期 12
·1642-1656
·
IF 4.263
Cao Zhanqi,Hao Zhaojun,Xin Ming,Yu Lugang,Wang Lei,Zhang Ying,Zhang Xinke,Guo Xiuli
Tumor cell-endothelial adhesion is one of the key steps in tumor cell haematogenous dissemination in metastasis and was previously shown to be mediated by interaction of galectin-3 with the transmembrane mucin protein MUC1. In this study, the effect of exogenous as well as endogenous galectin-3 on adhesion of two cell lines (low MUC1-expressing human prostate cancer PC-3M cells and non-small-cell lung cancer A549 cells) to monolayer of umbilical vein endothelial cells (HUVECs) was investigated. We found that suppression of endogenous galectin-3 expression reduced tumor cell adhesion to HUVECs and also decreased cell invasion and migration. Exogenous galectin-3 promoted tumor cell adhesion to HUVECs by entering cells. Both exogenous and endogenous galectin-3 upregulated the expression of β-catenin and increased β-catenin nuclear accumulation, and subsequently upregulated the expression of N-cadherin and CD44. We deduced that both exogenous as well as endogenous galectin-3 promoted low MUC1-expressing cancer cell adhesion to HUVECs by increasing the expression of N-cadherin and CD44 via an increase of nuclear β-catenin accumulation. These results were confirmed further by using a β-catenin/TCF transcriptional activity inhibitor, N-cadherin or CD44 siRNAs. Taken together, our results suggest a new molecular mechanism of galectin-3-mediated cell adhesion in cancer metastasis.
研究领域:
肿瘤学
·
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
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Yan Li,Huiwen Hou,Zengmei Liu,Wen Tang,Jie Wang,Lu Lu,Jiaai Fu,Didi Gao,Feiyan Zhao,XinQing Gao,Peixue Ling,Fengshan Wang,Feng Sun,Haining Tan
Neovascularization is crucial to the occurrence and progression of tumors, and the development of antiangiogenic drugs has essential theoretical value and clinical significance. However, antiangiogenesis therapy alone cannot meet the needs of tumor therapy. Meanwhile, polysaccharides are ideal drug carriers with promising applications in drug modification and delivery. In this research, we developed a novel redox and acid sensitive nanodrug (CDDP-CS-Cys-EA, CCEA) composed of chondroitin sulfate (CS), antiangiogenic peptide (endostatin2-alft1, EA) and chemotherapeutic drug (cisplatin, CDDP). CCEA exhibited redox and acid responsiveness, better blood hemocompatibility (hemolysis rate < 5 %), the ability to target tumors (CD44-mediated endocytosis), and strong antiangiogenesis and antitumor characteristics in vitro . Moreover, CCEA showed excellent antitumor activity and low toxicity in B16 xenograft mice. It also has been confirmed that CCEA induced tumor cell apoptosis through promoting the expression of Bax, suppressing the expression of Bcl-2, decreasing mitochondrial membrane potential, releasing cytochrome C (Cyto C), and enhancing the activities of Caspase 9 and Caspase 3. The results of this paper provided a theoretical basis and insight for the development of antitumor drugs.
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
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Bobo Fan,Qi Fan,Min Cui,Tingting Wu,Jinshen Wang,Hongmin Ma,Qin Wei
The serum level of soluble CD44 is directly associated with several clinicopathological parameters of malignant diseases. There is a great need for the development of an easy and cost-effective detection method for soluble CD44 for both the diagnosis and the treatment of cancers. In this work, a simple photoelectrochemical (PEC) method for the sensitive detection of serum-soluble CD44 is proposed based on the construction of a hybrid antifouling coating on the TiO2 substrate. Hyaluronic acid (HA) and poly(ethylene glycol) (PEG) are co-immobilized using a biomimetic one-step surface functionalization approach. The immobilized HA shows strong recognition abilities toward soluble CD44, and the synergistic antifouling effect achieved by the combination of PEG and HA improves the sensing specificity. Based on the inhibitory effect of CD44 recognition on the PEC signal of the TiO2 substrate, a PEC biosensor is developed with a wide response range and a low detection limit. The development of antibody-free biosensors may promote the application of soluble CD44 as a biomarker for the diagnosis and treatment of malignant diseases.
研究领域:
生物化学
·
生物医学工程
·
癌症研究
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL AND MOLECULAR MEDICINE
·
2025
·
IF 12.9
Yang Qihao,Wu Jianqun,Huang Songqiang,Zeng Jing,Jing Yihan,Wang Zhiyong,Zhang Chi,Wu Zenghui,Liu Song,Wang Zhao
Here we investigate the effects and mechanisms of eicosapentaenoic acid (EPA) in regulating chondrocyte mechanics during inflammation in the progression of osteoarthritis (OA). Primary porcine chondrocytes and human OA chondrocytes were isolated and cultured. Cell mechanical properties were measured using atomic force microscopy. RNA sequencing, immunocytochemistry, quantitative PCR and western blotting were used to elucidate associated signaling mechanisms. Porcine cartilage and human OA cartilage explants were collected. Human articular cartilage samples were obtained from ten donors. Anterior cruciate ligament transection surgery was performed to induce OA in male C57BL/6J mice. The therapeutic effects of EPA and activation of associated signaling were evaluated using histology, immunohistochemistry and micro-computed tomography. EPA reduced F-actin intensity and Young’s modulus in IL-1α-treated porcine chondrocytes and in human OA chondrocytes. Mechanistically, EPA inhibited IL-1α-induced increase in CD44 expression in porcine chondrocytes by suppressing phosphorylation of NF-κB subunits p65. In addition, EPA alleviated articular cartilage degeneration and decreased the expression of p-p65 and CD44 in IL-1α-treated porcine and human OA cartilage explants. Moreover, EPA suppressed the increase in Young’s modulus induced by CD44 ligands (A6 peptide and low-molecular-weight hyaluronic acid) in porcine chondrocytes. Finally, intraarticular injection of EPA emulsion-integrated hyaluronic acid injection attenuated OA-associated alterations in articular cartilage and subchondral bone and decreased CD44 expression in mice. Our data not only provide new insights into EPA’s chondroprotective actions and underlying mechanisms but also offer new evidence supporting the therapeutic efficacy of a novel EPA emulsion-integrated hyaluronic acid injection for OA treatment.
研究领域:
风湿病学
·
分子生物学
·
生物力学
·
骨科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Advances
·
2022
·Vol. 3
·期 11
·4707-4717
·
IF 0
Xiying Fan,Tingting Wang,Min Han,Yi Gu,Guochuan Sun,Xinying Peng,Qinghui Shou,Haipeng Song,Wenshuai Liu,Rui Nian
Colorectal cancer (CRC) is the second leading cause of cancer death among all malignancies. Drug delivery targeting tumor surface receptors improve therapeutic effects and lower side-effects since they can increase the drug accumulation in target tissues and cellular uptake. In this study, we established a pH- and redox-responsive drug delivery system based on mesoporous silica nanoparticles (MSNs) for the delivery of the anticancer drug doxorubicin hydrochloride (DOX). In this drug delivery system, MSNs-NH2 were modified with hyaluronic acid (HA) to form a highly loaded anticancer drug core; they were further coated with 11C12, a nanobody against carcinoembryonic antigen (CEA) to form a guiding outer layer (DOX@MSNs-HA-11C12). The accurate localization of nanoparticles would be mediated by two targeting molecules HA and nanobody 11C12, which target the CD44 receptor and the proximal membrane end of CEA on the surface of CRC cells, respectively. The release amount of DOX observed from in vitro drug release profiles increased as follows: pH 7.4 < pH 6.8 < pH 5.4, and (pH 7.4 + GSH) < (pH 6.8 + GSH) < (pH 5.4 + GSH), illustrating that the drug release could be accelerated in a weakly acidic environment as well as in the presence of reduced glutathione (GSH). In vitro cytotoxicity experiments showed that MSNs-HA-11C12 nanoparticles exhibited good biocompatibility and safety. Drug loaded nanoparticles modified by dual targeting molecules HA and 11C12 (DOX@MSNs-HA-11C12) led to higher LoVo CRC cell apoptosis in vitro, compared with DOX@MSNs-NH2 and DOX@MSNs-HA. Confocal laser scanning microscopy and fluorescence spectrophotometry further confirmed that the dual-targeting system significantly enhanced the uptake of DOX@MSNs-HA-11C12 by LoVo cells and the internalization of DOX was the highest, followed by DOX@MSNs-HA, DOX@MSNs-NH2, and DOX, subsequently. In this study, the nanobody targeting CEA was combined with the HA targeting CD44 receptor for the first time, which proved that the dual CEA/CD44 formulation can promote a more accurate drug delivery mode for CRC cells, and provide a basis for subsequent drug development for treating CRC and related cancers.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
ACS Omega
·
2022
·
IF 4.132
Xiudi Zhou,Qiang Chen,Chunjing Guo,Yanguo Su,Huimin Guo,Min Cao,Zhongxin Liu,Dandan Zhang,Ningning Diao,Huaying Fan,Daquan Chen
For the therapy attenuating renal ischemia–reperfusion (IR) injury, a novel drug delivery system was urgently needed, which could precisely deliver drugs to the pathological renal tissue. Here, we have prepared new nanomaterials with a reactive oxygen species (ROS)-responsive hydrogen sulfide (H2S) donor and hyaluronic acid that targets CD44 receptor. The novel material was synthesized and characterized via related experiments. Then, rapamycin was loaded, which inhibited kidney damage. In the in vitro study, we found that the micelles had ROS-responsiveness, biocompatibility, and cell penetration. In addition, the experimental results showed that the intracellular H2S concentration after administration was threefold higher than that of the control group. The western blot assay revealed that they have anti-inflammatory effects via H2S donor blocking the NF-κB signaling pathway. Consequently, the rising CD44 receptor-targeting and ROS-sensitive H2S donor micelles would provide a promising way for renal IR injury. This work provides a strategy for improving ischemia/reperfusion injury for pharmaceuticals.
研究领域:
药学
·
纳米技术
·
肾脏生理学
·
药物递送系统
·
炎症生物学
✓ 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）