INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Chunpeng Yang,Huiling Ma,Ze Liang,Ying Zhuang,Litao Hu,Kexin Zhang,Leixiao Huang,Min Li,Shubiao Zhang,Yuhong Zhen
Quercetin is a natural flavonoid found in many plants which has various pharmacological activities including antitumor effect. However, the poor water solubility and bioavailability limit the potential benefits of quercetin for patients. Thus, modifying quercetin structure and developing actively targeted drug delivery systems are extremely important for tumor precision therapy. Herein, polymer-drug conjugates dextran-quercetin (D-Q) and cRGD-dextran (R-D) were synthesized by grafting quercetin and polypeptide cRGDfk (Arg-Gly-Asp-(D-Phe)-Lys) to dextran. Then cRGD-modified dextran-quercetin polymer micelles (R-D-Q) were constructed by self-assembling of D-Q and R-D. R-D-Q micelles possessed appropriate particle size (133.4 nm), nearly neutral potential (8.14 mV) and excellent drug-loading efficiency (13.1 %) and achieved higher cytotoxicity, apoptosis induction and penetration to human breast cancer MCF-7 cells than the micelles unmodified with cRGD, which were ascribed to cRGD-integrin mediated transcytosis. R-D-Q micelles effectively suppressed tumor growth in tumor-bearing mice by delivering more quercetin throughout the tumor tissue. And R-D-Q micelles could promote the apoptosis of tumor cells by activating p38 and JNK signal pathways and suppressing ERK signal pathway. In addition, R-D-Q micelles had no damage to normal tissues of mice at therapeutic dose. These results indicate promising prospects for R-D-Q micelles as an effective drug delivery system against tumor.
研究领域:
药学
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肿瘤学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2014
·Vol. 11
·期 4
·3078-3086
·
IF 1.484
Ai‑Jun Li,Yue‑Hua Zheng,Guo‑Dong Liu,Wei‑Sheng Liu,Pei‑Cheng Cao,Zhen‑Fu Bu
The treatment of glioblastoma, and other types of brain cancer, is limited due to the poor transport of drugs across the blood brain barrier and poor penetration of the blood‑brain‑tumor barrier. In the present study, cyclic Arginine‑Glycine‑Aspartic acid‑D‑Tyrosine‑Lysine [c(RGDyK)], that has a high binding affinity to integrin αvβ3 receptors, that are overexpressed in glioblastoma cancers, was employed as a novel approach to target cancer by delivering therapeutic molecules intracellularly. The c(RGDyK)/docetaxel polylactic acid‑polyethylene glycol (DTX‑PLA‑PEG) micelle was prepared and characterized for various in vitro and in vivo parameters. The specific binding affinity of the Arginine‑Glycine‑Aspartic acid (RGD) micelles, to the integrin receptor, enhanced the intracellular accumulation of DTX, and markedly increased its cytotoxic efficacy. The effect of microtubule stabilization was evident in the inhibition of glioma spheroid volume. Upon intravenous administration, c(RGDyK)/DTX‑PLA‑PEG showed enhanced accumulation in brain tumor tissues through active internalization, whereas non‑targeted micelles showed limited transport ability. Furthermore, RGD‑linked micelles showed marked anti‑glioma activity in U87MG malignant glioma tumor xenografts, and significantly suppressed the growth of tumors without signs of systemic toxicity. In conclusion, the results of the present study suggest that ligand‑mediated drug delivery may improve the efficacy of brain cancer chemotherapy.
研究领域:
药学
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肿瘤学
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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
BIOMATERIALS
·
2025
·
IF 12.9
Nana Meng,Jiasheng Lu,Jianfen Zhou,Shengmin Yang,Chen Zhang,Ruiyi Jia,Yuan Ding,Yanning Bao,Jun Wang,Xiaopei Ma,Ruohan Chen,Zhixuan Jiang,Cao Xie,Linwei Lu,Weiyue Lu
One of the challenges for the clinical translation of active targeting nanomedicines is the adverse interactions between targeting ligands and blood components. Herein, a novel regularity, which reveals the interactions between cyclic RGD (Arg-Gly-Asp) peptide-modified liposomes and complement components in blood, is reported. As the nucleophilicity of arginine guanidine group within the cyclic RGD-like peptide increases, targeting liposomes potentiate complement cascade via the amplification loop of complement 3 (C3), ultimately leading to accelerated blood clearance, increased deposition in the reticuloendothelial system (RES) organs, enhanced immune responses, and potential side effects. By appropriately reducing the nucleophilicity of guanidine group, cyclic R2 peptide is designed for modification of liposomes to target integrin α v β 3 . Compared to the widely used targeting molecule c(RGDyK), R2 eliminates the negative effects of C3 opsonization and specific antibody production, significantly improves the in vivo immunocompatibility of targeting liposomes, and demonstrates superior anti-tumor efficacy in mouse models of orthotopic breast cancer and glioma. Thus, the proposed regularity of interactions between guanidine nucleophilicity and C3, along with the successful application of the low complement activation capacity targeting ligand R2, provides new insights for addressing challenges related to complement activation in the clinical translation of active targeting nanomedicines.
研究领域:
药学
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免疫学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2022
·
IF 6.458
Yuanyuan Li,Yangye Jin,Xiaofeng He,Yonghui Tang,Min Zhou,Wenjing Guo,Wenjun Miao
The development of integrated nanomedicine for prevention and early diagnosis of thrombosis is highly significant. Platelet plays a vital role in thrombotic disorders, offering an ideal target for thromboprophylaxis and imaging of thrombi . We herein fabricated cyclo(RGD) peptide-decorated AgNPs (designated cRGD-AgNPs) for active targeting platelet-rich thrombi. In vitro cytotoxicity and hemolysis assays demonstrated that cRGD-AgNPs have acceptable biocompatibility pattern. Both PEG-AgNPs (non-targeted version) and cRGD-AgNPs can inhibit agonist-mediated platelet aggregation , whereas the latter exhibited significant attenuation on platelet activation and adhesion onto collagen and fibrinogen matrix. Furthermore, the superior binding ability of cRGD-AgNPs with platelet-rich thrombus was demonstrated in static/dynamic condition in vitro . In vivo studies revealed that cRGD-AgNPs could actively target thrombi in a mouse model of carotid artery thrombi with favorable safety. Our results here suggest that cRGD-AgNPs with intrinsic anti-platelet potential might be promising nano theranostics for thromboprophylaxis and active thrombus targeting.
研究领域:
纳米医学
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血液学
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生物材料
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 1
·276
·
IF 5.4
Xuanping Zhao,Chuan Liu,Zichao Wang,Yingyuan Zhao,Xuyang Chen,Haizhen Tao,Hong Chen,Xueqin Wang,Shaofeng Duan
Numerous nanocarriers have been developed to deliver drugs for the treatment of hepatocellular carcinoma. However, the lack of specific targeting ability, the low administration efficiency, and insufficient absorption by hepatocellular carcinoma cells, severely limits the therapeutic effect of the current drugs. Therefore, it is still of great clinical significance to develop highly efficient therapies with few side effects for the treatment of hepatocellular carcinoma. Herein, we developed a highly effective nanocarrier, cyclic RGD peptide-conjugated magnetic mesoporous nanoparticles (RGD[email protected]NPs), to deliver the chemotherapeutic drug doxorubicin (DOX) to human hepatocellular carcinoma HepG2 cells, and further explored their synergistic apoptosis-promoting effects. The results showed that the preparedRGD[email protected]NPs had good stability, biosafety and drug-loading capacity, and significantly improved the absorption of DOX by HepG2 cells, and that theRGD[email protected]@DOX NPs could synergistically promote the apoptosis of HepG2 cells. Thus, this cyclic RGD peptide-modified magnetic mesoporous silicon therapeutic nanosystem can be regarded as a potentially effective strategy for the targeted treatment of hepatocellular carcinoma.Keywords:cyclic RGD peptide;anticancer drug delivery;targeted nanoparticles;hepatocellular carcinoma;apoptosis
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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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2010
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IF 5.949
Changyou Zhan,Bing Gu,Cao Xie,Jin Li,Yu Liu,Weiyue Lu
The use of glioblastoma-targeted drug delivery system facilitates efficient delivery of chemotherapeutic agents to malignant gliomas in the central nervous system while minimizing high systemic doses associated with debilitating toxicities. To employ the high binding affinity of a cyclic RGD peptide (c(RGDyK), cyclic Arginine–Glycine–Aspartic acid- d -Tyrosine-Lysine) with integrin α v β 3 over-expressed on tumor neovasculature and U87MG glioblastoma cells, we prepared paclitaxel-loaded c(RGDyK)-Poly(ethylene glycol)- block -poly(lactic acid) micelle (c(RGDyK)-PEG-PLA-PTX). In vitro physicochemical characterization of these novel micelles showed satisfactory encapsulated efficiency, loading capacity and size distribution. In vitro cytotoxicity studies proved that the presence of c(RGDyK) enhanced the anti-glioblastoma cell cytotoxic efficacy by 2.5 folds. The binding affinity of c(RGDyK)-PEG-PLA micelle with U87MG cells was also investigated. The competitive binding IC 50 value of c(RGDyK)-PEG-PLA micelle was 26.30 nM, even lower than that of c(RGDyK) (56.23 nM). In U87MG glioblastoma-bearing nude mice model, biodistribution of 125 I-radiolabeled c(RGDyK)-PEG-PLA or DiR encapsulated micelles and anti-glioblastoma pharmacological effect was investigated after intravenous administration. c(RGDyK)-PEG-PLA micelle accumulated in the subcutaneous and intracranial tumor tissue, and when loaded with PTX (c(RGDyK)-PEG-PLA-PTX), exhibited the strongest tumor growth inhibition among the studied paclitaxel formulations. The anti-glioblastoma effect of c(RGDyK)-PEG-PLA-PTX micelle was also reflected in the median survival time of mice bearing intracranial U87MG tumor xenografts where the median survival time of c(RGDyK)-PEG-PLA-PTX micelle-treated mice (48 days) was significantly longer than that of mice treated with PEG-PLA-PTX micelle (41.5 days), Taxol® (38.5 days) or saline (34 days). Therefore, our results suggested that c(RGDyK)-PEG-PLA micelle may be a potential drug delivery system in the treatment of integrin α v β 3 over-expressed glioblastoma.
研究领域:
药学
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肿瘤学
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神经科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Pengpeng Guan,Caijie Yuan,Jiali Li,Kun Yu,Ruiqi Xie,Enling Hu,Weiwei Ding,Guangqian Lan,Fei Lu
In the treatment of thrombosis, conventional nanocarriers inevitably have problems, such as adverse reactions and difficulties in synthesis. Inspired by the concept of ‘medicine food homology,’ we extracted and purified natural exosomes from mulberry leaves as carriers for the delivery of urokinase-type plasminogen activator (uPA) for targeted therapy. The obtained mulberry leaf exosomes (MLE) possessed a desirable hydrodynamic particle size (119.4 nm), a uniform size distribution (polydispersity index = 0.174), and a negative surface charge (−23.3 mv). Before loading with uPA, MLE were grafted with cyclic RGD (cRGD) to selectively bind activated platelets for thrombus targeting. The cytometry studies revealed that MLE@cRGD has a high thrombus targeting ability about 74.3 %. Animal tests demonstrated that the delivered uPA could dissolve clots almost completely in femoral vein thrombosis models. In addition, MLE could remodel venous microenvironments by effectively eliminating reactive oxygen species (ROS) and promoting the phenotypic transformation of macrophages from M1 to M2 for venous tissue repair.
研究领域:
药理学
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纳米技术
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治疗学
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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
Journal of Materials Chemistry B
·
2019
·Vol. 8
·期 3
·447-453
·
IF 5.047
Sen Ye,Yang Liu,Yi Lu,Yuqin Ji,Lianlian Mei,Mingwen Yang,Xiaoxuan Gong,Qian Gu,Di Li,Fang Yang,Chun-Jian Li
Thrombotic disease is a serious threat to human health. The rapid and accurate detection of thrombosis is still a clinical challenge. To achieve the accurate diagnosis of thrombosis with magnetic resonance imaging (MRI), nanomaterials-based contrast agents have been developed in recent years. In this study, cyclic RGD functionalized liposomes targeted to the activated platelets are developed for thrombosis dual-mode MRI. The cyclic RGD functionalized liposomes (cRGD@MLP-Gd) encapsulated with gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) and superparamagnetic iron oxide (SPIO) are prepared, and their thrombus-targeted T1 and T2 MRI potential is evaluated in vitro and in vivo. Results show that cRGD@MLP-Gd could actively bind to the activated platelets and gradually accumulate at the thrombus site with a T1 − T2 contrast enhancement imaging effect in vitro. In in vivo MRI experiments, cRGD@MLP-Gd exhibits a T2 contrast enhancement at 1 h after intravenous administration, followed by a visibly larger T1 contrast enhancement at the thrombus site. This dynamic property showed that cRGD@MLP-Gd could actively bind to thrombus and possessed an enhanced T1 and T2 dual-mode MRI effect in vivo. Our results establish the characterization, feasibility and superiority of cRGD@MLP-Gd for the rapid identification of thrombosis, showing great potential to improve diagnostic accuracy and sensitivity to thrombosis of the MRI technique.
研究领域:
医学影像
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纳米医学
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诊疗学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
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IF 5.8
Wenbo Wang,Shihao Zhou,Zhaoyi Cheng,Dong Ma,Tao Liu
CRISPR-Cas9 technology has been proven to be the most straightforward and accurate tool for gene therapy, but some limitations, such as the inefficient transfection or inability to precisely target, prevent the gene therapy from achieving the desired therapeutic effect. To overcome these, a kind of glutathione-sensitive cationic vectors, hyperbranched polyamide amine (HPAA) was designed for Delivery of CRISPR-Cas9 RNA plasmid, and the cyclic RGD (Arg-Gly-Asp) was conjugated for the targeted treatment of nasopharyngeal carcinoma (NPC). Disulfide bonds in HPAA segments can specifically respond to the high glutathione concentration in the tumor microenvironment. Meanwhile, RGD could especially interact to the integrin α v β 3 receptors which are highly expressed on the surface of NPC tumor cells. The results showed that more HPAA-RGD/SGK3-gRNA complexes could be uptaken by NPC HNE-1 cells after RGD was conjugated, and then the plasmid could be accumulated in the NPC tumor as well, which may assure the satisfied NPC therapy effect in vivo. In transfection assays, this complex showed the acceptable gene transfection efficiency in vitro and the obvious tumor inhibition effect in vivo, suggested a potential application in gene therapy to NPC.
研究领域:
分子生物学
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基因治疗
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癌症研究
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纳米技术
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Dan Chen,Bowen Li,Songhua Cai,Peng Wang,Shuwen Peng,Yuanzhi Sheng,Yuanyuan He,Yueqing Gu,Haiyan Chen
Dual targeting towards both extracellular and intracellular receptors specific to tumor is a significant approach for cancer diagnosis and therapy. In the present study, a novel nano-platform (AuNC-cRGD-Apt) with dual targeting function was initially established by conjugating gold nanocluster (AuNC) with cyclic RGD (cRGD) that is specific to α v β 3 integrins over-expressed on the surface of tumor tissues and aptamer AS1411 (Apt) that is of high affinity to nucleolin over-expressed in the cytoplasm and nucleus of tumor cells. Then, AuNC-cRGD-Apt was further functionalized with near infrared (NIR) fluorescence dye (MPA), giving a NIR fluorescent dual-targeting probe AuNC-MPA-cRGD-Apt. AuNC-MPA-cRGD-Apt displays low cytotoxicity and favorable tumor-targeting capability at both in vitro and in vivo level, suggesting its clinical potential for tumor imaging. Additionally, Doxorubicin (DOX), a widely used clinical chemotherapeutic drug that kill cancer cells by intercalating DNA in cellular nucleus, was immobilized onto AuNC-cRGD-Apt forming a pro-drug, AuNC-DOX-cRGD-Apt. The enhanced tumor affinity, deep tumor penetration and improved anti-tumor activity of this pro-drug were demonstrated in different tumor cell lines, tumor spheroid and tumor-bearing mouse models. Results in this study suggest not only the prospect of non-toxic AuNC modified with two targeting ligands for tumor targeted imaging, but also confirm the promising future of dual targeting AuNC as a core for the design of prodrug in the field of cancer therapy.
研究领域:
纳米技术
·
癌症生物学
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药物科学
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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
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Yu Zhao,Huangmei Zhou,Longliang Qiao,Jinming Xu,Rodolphe Antoine,Lunhua Deng,Sanjun Zhang,Haifeng Ye
Precise measurements of tumor pH is essential for early cancer diagnose, treatment planning, and the development of anti-cancer drugs. Herein, we present a pH-sensitive, ratiometric fluorescent biosensor with tumor-targeting capabilities for real-time in vivo tumor pH detection. The biosensor, composed of glutathione-protected gold nanoclusters (AuNCs) conjugated with fluorescein-isothiocyanate (FITC), provides a reliable ratiometric fluorescence signal response to pH. The cyclic arginine-glycine-aspartic acid (c(RGDyC)) peptide was integrated into the sensor (denoted as c(RGDyC)-FITC@AuNCs) to confer tumor-targeting specificity. Upon excitation at 488 nm, c(RGDyC)-FITC@AuNCs exhibited dual-channel emissions at 515 nm and 710 nm, the ratio of which showed a 17-fold change across a pH range of 5.5 to 8.0. In addition, c(RGDyC)-FITC@AuNCs demonstrated excellent biocompatibility, long-term photostability, and low toxicity, enabling the quantitative monitoring of the pH changes during tumor cell apoptosis in real-time. Moreover, using tumor-bearing mouse models with induced acid-alkaline variations, c(RGDyC)-FITC@AuNCs successfully visualized and dynamically tracked in situ tumor pH. This biosensor offers a sensitive and accurate tool for tumor diagnosis, with significant potential in biomedical research and clinical studies.
研究领域:
生物医学工程
·
纳米技术
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生物化学
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癌症研究
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分子成像
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荧光传感
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药学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2020
·
IF 5.115
Xiang Li,Qian Zou,Jing Zhang,Peng Zhang,Xiong Zhou,Satya Siva Kishan Yalamarty,Xinli Liang,Yali Liu,Qin Zheng,Jianqing Gao
Purpose Folic acid and cyclic arginylglycylaspartic acid peptides were introduced to the surface of negatively charged lipid-coated hybrid polydopamine-cysteine cores for the delivery of epirubicin (EPI) (E/PCF-NPs). The combined chemo-photothermal therapy using E/PCF-NPs for triple-negative breast cancer was evaluated. Materials and Methods The temperature elevation and thermal toxicity of nanoparticles were studied. The morphology and properties of E/PCF-NPs were characterized by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Physicochemical properties, including particle size, zeta potential, drug loading, entrapment efficiency (EE%), stability and in vitro release, were determined. The cell viability, reactive oxygen species (ROS) levels, ratios of oxidized nicotinamide adenine dinucleotide to its reduced form (NAD + /NADH), apoptosis assays, and cellular uptake of E/PCF-NPs were determined on 4T1 cells. Pharmacokinetic studies and tissue distributions were performed and detected by an ultra-high performance liquid chromatography/mass spectrometry system. The antitumor effects of E/PCF-NPs under near-infrared (NIR) laser irradiation were also evaluated. Results The sphere-like morphology of E/PCF-NPs showed a high EE%, uniform size of 106.7 nm, remarkable stability, and highly improved cytotoxicity under NIR laser, when compared to that of photothermal treatment alone. In vitro release of EPI from E/PCF-NPs was pH sensitive, and a greater response was achieved under NIR laser irradiation. Compared to chemotherapy or photothermal treatment alone, the combined treatment in vitro significantly inhibited the survival rate of 4T1 cells to 17.7%, induced ROS generation, and reduced NAD + /NADH significantly. Treatment with E/PCF-NPs under irradiation induced 4T1 cell apoptosis in approximately 93.6% cells. In vitro cellular uptake of E/PCF-NPs was time-dependent. The long-circulating and higher tumor accumulation of E/PCF-NPs resulted in complete ablation of breast tumor tissue through the enhanced photothermal effect by NIR laser irradiation-mediated cell apoptosis. Conclusion E/PCF-NPs show enhanced anti-cancer effects due to synergistic effects of chemotherapy with photothermal therapy and may be potential therapeutic agents for cancer treatment.
研究领域:
肿瘤学
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纳米技术
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药学
·
生物医学工程
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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）