BIOMEDICINE & PHARMACOTHERAPY
·
2016
·
IF 2.326
Zhenhua Fang,Yanpeng Sun,Hong Xiao,Peng Li,Ming Liu,Fan Ding,Wusheng Kan,Runsheng Miao
Osteosarcoma is the most common primary malignant bone tumor in the pediatric age group, and chemotherapy directed by targeted nanoparticulate drug delivery system represents a promising approach for osteosarcoma treatment recently. Here, we designed and developed a novel DOX-loaded targeted polymeric micelle self-assembled from RGD-terminated poly(ethylene glycol)- block -poly (trimethylene carbonate) (RGD-PEG-PTMC) amphiphilic biodegradable block copolymer , for high-efficiency targeted chemotherapy of osteosarcoma. Notably, the RGD-installed DOX-loaded biodegradable polymeric micelle (RGD-DOX-PM) with drug loading efficiency of 57%–73% displayed a narrow distribution (PDI = 0.05–0.12) with average sizes ranging from 46 to 73 nm depending on the DOX loading content. The release amount of DOX from RGD-DOX-PM achieved 63% within 60 h under physiological condition. Interestingly, MTT assays in MG-63 and MNNG/HOS osteosarcoma cells exhibited that half-maximal inhibitory concentration (IC 50 ) value of RGD-DOX-PM was much lower than its non-targeted counterpart (DOX-PM), implying RGD decorated nanoparticles had enhanced cell targeting ability and led to more effective anti-tumor effect. Furthermore, the targeting ability of RGD-DOX-PM was confirmed by in vitro flow cytometry and confocal laser scanning microscopy (CLSM) imaging assays, where the results showed more RGD-DOX-PM were taken up by MG-63 cells than that of DOX-PM. Therefore, this RGD decorated DOX-loaded polymeric micelle is promising for targeted chemotherapy of osteosarcoma.
研究领域:
肿瘤学
·
药剂学
·
生物材料学
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DOI
PubMed
高影响因子
Journal of Materials Research and Technology-JMR&T
·
2021
·
IF 5.039
Yuzhe Chen,Wenxuan Zhao,Honglian Dai
Chitosan (CS) is a type of natural polysaccharide, widely used as a biomaterial on account of its great biocompatibility and the multitudes of functional groups on the long chitosan chain, making it easy for property augmentations. Nevertheless, the lack of workability and mechanical capacity limits the applications. Herein, electrospinning was chosen to fabricate oriented chitosan/polyethylene oxide (PEO) nanofibres decorated by integrin-targeting polypeptides (RGD, Arg-Gly-Asp), which is essential for cell adhesion. At the same time, porous PLGA-PEG membranes were taken as a shell of the composite film, which can provide mechanical support for the scaffold. Adequate topological anisotropic information from oriented nanofibres helps the scaffold simulate the natural axon structure, which can induce accelerated regeneration of neurotmesis. Moreover, β-Tricalcium Phosphate (β-TCP) nanoparticles were brought into nanofibers to neutralize the acidic environment produced by the degeneration of PLGA-PEG. Cell viability tests at the in vitro level and dorsal root ganglion (DRG, 1-day sucking SD rat) co-culture detection proved that the scaffold possesses excellent biocompatibility while guiding oriented regeneration of damaged nerves. In this study, a CS-RGD/PEO/β-TCP/PLGA-PEG porous composite scaffold with low cytotoxicity was fabricated. The scaffold can not only lead to the oriented growth of nerves but also has selectivity, which can help nutrient exchange while inhibiting the invasion of fibrous tissue.
研究领域:
生物医学工程
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材料科学
·
神经再生
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产品关联
DOI
高影响因子
Journal of Nanomaterials
·
2016
·
IF 1.758
Xiaochao Qu,Xiaoxiao Li,Jingning Liang,Yanran Wang,Muhan Liu,Jimin Liang
Gold nanomaterials as computed tomography (CT) contrast agents at lower X-ray dosage to get a higher contrast have advantages of longer imaging time and lower toxic side effects compared to current contrast agents. As a receptor for Cyclo (Arg-Gly-Asp-D-Phe-Lys) (RGD) peptide, integrin is overexpressed on some tumor cells and tumor neovasculature. In this paper, we conjugated the RGD peptide on the surface of gold nanorods (AuNRs), designated as RGD-AuNRs, a promising candidate in applications such as tumor targeting and imaging capability for micro-CT imaging. Integrin -positive U87 cells and integrin -negative HT-29 cells were chosen to establish animal models relatedly and then texted the tumor targeting ability and imaging capability of RGD-AuNRs in vitro and in vivo. The MTT assay and stability measurement showed that RGD-conjugation eliminated their cytotoxicity and improved their biocompatibility and stability. Dark-field imaging of U87 cells and HT-29 cells testified the binding affinities and uptake abilities of RGD-AuNRs, and the results showed that RGD-AuNRs were more specifical to U87 cells. The enhanced micro-CT imaging contrast of intramuscular and subcutaneous injection illustrated the feasibility of RGD-AuNRs to be contrast agents. Furthermore, the micro-CT imaging of targeting U87 and HT-29 tumor models verified the targeting abilities of RGD-AuNRs.
研究领域:
医学影像学
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纳米生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
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
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2019
·
IF 2.606
Mei Wei,Taicheng Lu,Zhenzhen Nong,Guo Li,Xin Pan,Yiming Wei,Yanfang Yang,Nini Wu,Jing Huang,Meishi Pan,Xuehua Li,Fayan Meng
Cancer cell therapy using redox response and targeted drug delivery systems can increase therapeutic effects of anti-cancer therapy. Here, we report a redox-responsive drug carrier based on nanoscale Graphene Oxide (GO) loaded with Doxorubicin (DOX). In this drug carrier demonstration, we utilized Arginine-glycine-aspartic acid (RGD) peptide, aminated polyethylene glycol (6ARM-PEG-NH 2 , PEG-NH 2 ) to functionalize the GO. To integrate the carrier with a redox responsive property, we utilized disulfide linkages (3,3′-dithiodipropionic acid (DTPA)), which can be cleaved by glutathione (GSH) combined with the PEG-NH 2 . Our results show that DOX is rapidly released in a pH = 5.50 PBS solution with GSH concentration of 10 mM. The drug-loading system (RGD-GO-PEG-S-S-DOX) combined with photo-thermotherapy possesses good inhibition activity of Hep-G2 cells at a relatively low concentration. When the concentration of RGD-GO-PEG-S-S-DOX was 1.56 μg/mL, the inhibition activity of Hep-G2 cells was 78%. Because tumor cells generally exhibit a higher concentration of GSH than normal ones, and tumor blood vessels are distorted and dilated, and the blood flow resistance tends to be large, tumor cells are more sensitive to temperature changes than normal tissues. Thus, drug delivery systems, like the one we studied, have potential applications in a therapeutic strategy for the treatment of liver cancer.
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2011
·
IF 4.304
Lihong Zhang,Saijie Zhu,Lili Qian,Yuanying Pei,Yongming Qiu,Yanyan Jiang
This work was based on our recent studies that a promising conjugate, RGD-modified PEGylated polyamidoamine (PAMAM) dendrimer with doxorubicin (DOX) conjugated by acid-sensitive cis -aconityl linkage (RGD-PPCD), could increase tumor targeting by binding with the integrin receptors overexpressed on tumor cells and control release of free DOX in weakly acidic lysosomes. To explore the application of RGD-PPCD to glioma therapy, the effects of the conjugate were further evaluated in glioma model. For comparative studies, DOX was also conjugated to PEG–PAMAM by acid-insensitive succinic linkage to produce the PPSD conjugates, which was further modified by RGD to form RGD-PPSD. In vitro cytotoxicity of the acid-sensitive conjugates against C6 cells was higher than that of the acid-insensitive ones, and further the modification of RGD enhanced the cytotoxicity of the DOX-polymer conjugates as a result of the increased cellular uptake of the RGD-modified conjugates by C6 cells. In vivo pharmacokinetics, biodistribution and antitumor activity were investigated in an orthotopic murine model of C6 glioma by i.v. administration of DOX-polymer conjugates. In comparison with DOX solution, all the conjugates showed significantly prolonged half-life and increased AUC and exhibited higher accumulation in brain tumor than normal brain tissue. Although RGD-PPCD was more than 2-fold lower tumor accumulation than RGD-PPSD, it exhibited the longest survival times among all treatment groups, and therefore, RGD-PPCD conjugate provide a desirable candidate for targeted therapy of glioma.
研究领域:
药理学
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肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Wentao Xu,Jiajia Zheng,Jiaqi Zhang,Houhui Shi,Weili Peng,Yang Liu,Guodong Feng,Yuguang Wang,Yi-Jun Liang,Jun Chen
Background Liver cancer is one of the most prevalent cancers globally, with approximately 90% of primary liver cancers being hepatocellular carcinomas (HCC). However, current systemic treatment options (whether monotherapy or combination therapy) are limited and offer only modest survival benefits. The effectiveness of a drug is largely determined by its concentration at the target site. Therefore, an effective drug delivery system must enhance drug accumulation at the target site, enable selective drug release there, and facilitate escape from lysosomes.Methods cRGD-Lipo@Ce6/DOX was prepared by modifying c(RGDyK) onto the surface of drug-loaded liposomes containing Chlorin e6 (Ce6) and doxorubicin (DOX) through an amide reaction. The targeting capability and uptake mechanism of cRGD-Lipo@Ce6/DOX for HCC were analyzed using flow cytometry. To investigate drug release mechanisms and changes in subcellular distribution following ultrasound stimulation, further studies were conducted. The therapeutic efficacy and biosafety of this dual-modality therapy were then evaluated in an HCC subcutaneous tumor-bearing mouse model.Results The prepared nanocomplex exhibits a surface charge of −9.91 ± 2.94 mV and an apparent size of 118.07 ± 1.46 nm. Modification of the RGD cyclic peptide on the surface of the drug-carrying liposomes enhanced the targeting and penetration efficiency for HCC. In vitro experiments on drug uptake mechanisms and release demonstrated that reactive oxygen species (ROS) generated by sonodynamic therapy (SDT) promote effective drug release from the carrier into the non-lysosomal region. The combined SDT and chemotherapy treatment achieved a 94% tumor inhibition rate and showed excellent biosafety in HCC subcutaneous tumor-bearing mice.Conclusion Therefore, the effectiveness of the combination treatment strategy utilizing SDT in conjunction with chemotherapy provides additional treatment options for patients with HCC.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
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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
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ORGANIC & BIOMOLECULAR CHEMISTRY
·
2019
·Vol. 17
·期 15
·3853-3860
·
IF 3.49
Leixia Mei,Keming Xu,Ziran Zhai,Suyun He,Tingting Zhu,Wenying Zhong
Drug incorporation in hydrogels often brings undesirable effects on the stability or mechanical properties of the system. To address this problem, we report the design and synthesis of a RGD-derived peptide conjugate (1-RGDH) for its co-assembly with a commonly used chemotherapeutic drug, doxorubicin (DOX), that formed electrostatic interactions with the 1-RGDH peptide and reinforced the supramolecular network of nanofibers within the matrix of the hydrogel. The hybrid hydrogel demonstrated excellent viscoelastic and shear-thinning properties that greatly facilitated the development of injectable drug delivery systems. Furthermore, it demonstrated a unique pH responsive release of DOX under weakly acidic conditions, paving ways for the controlled release of drug cargos in a typical tumor microenvironment with mild acidity. Finally, the DOX-incorporated hydrogel exhibited a superior anti-tumor efficacy in non-small-cell lung cancer cells A549 compared to the aqueous solution of free DOX, with an integrin receptor-mediated endocytosis pathway revealed for the cellular uptake of DOX-incorporated nanofibers.
研究领域:
药物递送系统
·
生物材料
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2016
·
IF 8.854
Zhengyang Jia,Lina Song,Fengchao Zang,Jiacheng Song,Wei Zhang,Changzhi Yan,Jun Xie,Zhanlong Ma,Ming Ma,Gaojun Teng,Ning Gu,Yu Zhang
Developing ultrasensitive contrast agents for the early detection of malignant tumors in liver is highly demanded. Constructing hepatic tumors specific targeting probes could provide more sensitive imaging information but still faces great challenges. Here we report a novel approach for the synthesis of ultra-small Fe 3 O 4 nanoparticles conjugated with c(RGDyK) and their applications as active-target T 1 -weighted magnetic resonance imaging (MRI) contrast agent (T 1 -Fe 3 O 4 ) for imaging tiny hepatic tumors in vivo . RGD-modified T 1 -Fe 3 O 4 nanoprobes exhibited high r 1 of 7.74 mM -1 s -1 and ultralow r 2 /r 1 of 2.8 at 3 T, reflecting their excellent T 1 contrast effect at clinically relevant magnetic field. High targeting specificity together with favorable biocompatibility and strong ability to resist against non-specific uptake were evaluated through in vitro studies. Owing to the outstanding properties of tumor angiogenesis targeting with little phagocytosis in liver parenchyma, hepatic tumor as small as 2.2 mm was successfully detected via the T 1 contrast enhancement of RGD-modified T 1 -Fe 3 O 4 . It is emphasized that this is the first report on active-target T 1 imaging of hepatic tumors, which could not only significantly improve diagnostic sensitivity, but also provide post therapeutic assessments for patients with liver cancer.
研究领域:
医学影像学
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2014
·
IF 2.202
Ke Wang,Xiaofeng Zhang,Lihong Zhang,Lili Qian,Chang Liu,Jiajun Zheng,Yanyan Jiang
Context: The sustained release implants can be directly implanted in tumor site by surgery and are promising for cancer treatment.Objective: RGD-modified PEGylated polyamidoamine (PAMAM) dendrimer with doxorubicin (DOX) conjugated by acid-sensitive linkage (RGD-PPCD) was a potential conjugate for tumor-targeted therapy. In order to enhance tumor retention ability and long-term effect of drug, we developed the DOX and its conjugate implants using poly(dl-lactic-co-glycolic acid) (PLGA), poly(dl-lactic acid) (PLA) and polyethylene glycol (PEG) as carrier materials.Methods: The implants were prepared by a simple solvent evaporation method. Different formulations with varying ratios of three polymers were designed, prepared and evaluated on the basis of viscosity, in vitro release and drying time. Furthermore, in vivo biodistribution and antitumor activity of the implants were studied in mice with subcutaneous C6 xenografts.Results: The optimized formulation was obtained with the 3:1 ratio of PLGA/PLA (w/w) and 1% PEG (wt.%). The drug release behavior of DOX, PPCD and RGD-PPCD implants prepared by the optimized formulation was similar according to the assessment of similarity factor f2, and the release curves were fell into three phases, including a lag-period, then the second phase which was consistent with zero-order model followed by a plateau. Data of total DOX remained in implants indicated the release were faster in vivo than in vitro. Moreover, intratumoral drug amount of RGD-PPCD implants was the highest 45 days after implantation. Correspondingly, the RGD-PPCD implants exhibited the strongest antitumor activity compared with PPCD and free DOX implants.Discussion and conclusion: This paper presents an exploratory research on macromolecule-drug conjugates, including RGD-PPCD and PPCD, which have the potential to be developed into long-term effect implants for tumor therapy with high efficiency and low systematic toxicity.
研究领域:
肿瘤学
·
药剂学
✓ 已验证
DOI
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
·
血液学
·
生物材料
✓ 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）