COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Yi Zhang,Zhongbing Huang,Zhi Wu,Guangfu Yin,Lei Wang,Fabao Gao
Absence of efficient targeting limits the application of magnetic nanochains (NCs) in the diagnosis of early brain cancer. Herein, dextran-coated NCs (more than 100 nm length and ∼10 nm cores diameter), which were modified by cyclic pentapeptide c(RGDyC) or chlorotoxin (CTX) as the targeting molecules, were fabricated via carbodiimide chemistry and thiol technique. The analysis results revealed that the obtained slender NCs exhibited good biocompatibility, superparamagnetic property, high transverse relaxivity ( R 2 ) and longer blood circulation time. The test results of human umbilical vein endothelial cells and U251 human glioma cells indicated that the conjugation of c(RGDyC) could obviously increase the cyto-internalization of c(RGDyC)-NCs, however, CTX modification could significantly enhance accumulation of CTX-NCs in U251 cells, leading to cellular apoptosis. The results of in vivo biodistribution tests and in vivo magnetic resonance (MR) imaging indicated that, although the c(RGDyC)-NCs could target early glioma to some extent and obviously enhance the contrast of MR imaging, CTX-NCs possessed higher tumor-targeting ability and good inhibition effect than the c(RGDyC)-NCs, suggesting that CTX-NCs are promising candidates for the diagnosis and therapy of early glioma.
研究领域:
生物医学工程
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肿瘤学
·
分子影像学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Guowen Wang,Zuyi Wang,Chuankui Li,Guixin Duan,Kangwu Wang,Qicai Li,Tao Tao
One approach to improve the targeted therapeutic efficiency of lung cancer is to deliver drugs using nano-scaled systems. In this study, RGD peptide-modified, paclitaxel (PTX) prodrug-based, dual-drugs loaded, and redox-sensitive lipid-polymer nanoparticles were developed and the in vitro and in vivo antitumor efficiency was evaluated in lung cancer cells and tumor bearing animal models. RGD-modified PTX and cisplatin (CDDP) loaded LPNs (RGD-ss-PTX/CDDP LPNs) have sizes around 190 nm, and zeta potentials of −35 mV. The half-maximal inhibitory concentration (IC50) values were 26.7 and 75.3 μg/mL for drugs loaded LPNs and free drugs combination, which indicates significantly higher antitumor activity of LPNs than free drugs. RGD-ss-PTX/CDDP LPNs also exhibited the best antitumor efficiency in vivo , which inhibited the tumor size of mice from 1486 mm 3 to 263 mm 3 . The results illustrated that the system could successfully load drugs and achieve synergistic combination lung cancer treatment efficiency with lower systemic toxicity compared with free drugs counterparts. The resulting system could be facilitated as a promising targeted nanomedicine for the treatment of lung cancer.
研究领域:
药学
·
肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 48
·42109-42119
·
IF 3.289
Gang Pan,Yi-jie Bao,Jie Xu,Tao Liu,Cheng Liu,Yan-yan Qiu,Xiao-jing Shi,Hui Yu,Ting-ting Jia,Xia Yuan,Ze-ting Yuan,Pei-hao Yin,Yi-jun Cao
We report on the fabrication of a multifunctional polymeric prodrug covalently linked with an anticancer drug (bufalin, BUF) and tumor-targeting peptide (RGD) and investigate its anticancer performance against colon cancer in mice. The polymerizable monomer, 3-((2-(methacryloyloxy)ethyl) thio)propanoic acid (BSMA), was synthesized first. Atom radical transfer polymerization (ATRP) of BSMA and oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) afforded random copolymers, P(OEGMA-co-BSMA). The polymeric prodrug of BUF, P(OEGMA-co-BUF), was obtained by an esterification reaction between the carboxyl groups of P(OEGMA-co-BSMA) and the hydroxyl group of BUF. Finally, a tumor-targeting polymeric prodrug, P(OEGMA-co-BUF-co-RGD), was obtained via an aminolysis reaction of P(OEGMA-co-BUF) in the presence of RGD and the final drug content was determined to be ∼32.9 wt%. In aqueous media, P(OEGMA-co-BUF-co-RGD) self-assembles into micelles and the hydrodynamic diameter (Dh) of the micelles was determined to be ∼33.0 (±2.5) nm by dynamic laser light scattering (LLS). It was demonstrated that the tumor-targeting polymeric prodrug showed improved anticancer performance both in vitro and in vivo in comparison with that of free BUF.
研究领域:
药学
·
肿瘤学
·
生物材料
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产品关联
DOI
高影响因子
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
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Jing Wang,Congcong Lin,Xiaoyang Li,Junyao Wei,Yihua Wang,Rongtao Li,Yan Ming,Jingling Tang,Jiaxin Liu,Manjie Zhang,Hongyu Ji
Myocardial infarction (MI) is a leading cause of heart failure and death in cardiovascular diseases. Most drug trials currently fail due to inadequate local drug activity and side effects. In this study, we developed a novel polydopamine (PDA) nano delivery system that carries sodium ferulate (SF) and is modified with RGD peptides (SF/RGD-PDA NPs) for precise targeted delivery. SF is a clinical adjuvant for cardiovascular and cerebrovascular diseases but lacks targeting and has a short half-life. PDA, known for its excellent biocompatibility and surface modifiability, serves as an effective carrier. SF was loaded onto PDA through π-π stacking, while RGD was attached via a Michael addition reaction, resulting in stable SF/RGD-PDA NPs with an average particle size of 206.13 nm. In vitro and in vivo studies indicate that this targeted formulation has good safety. Targeting studies showed a 2.19-fold increase in nanoparticle accumulation in the heart and a 5.94-fold increase in cellular uptake efficiency. Pharmacodynamic studies revealed a 1.45-fold increase in endothelial cell proliferation, a 1.46-fold increase in angiogenesis rate, and a significant reduction in MI area. These findings suggest that SF/RGD-PDA NPs can improve endothelial cell function and reduce MI area through targeted delivery.
研究领域:
药学
·
心血管病学
·
纳米医学
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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
·
免疫学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yaning Ge,Xin Zhu,Zhengxian Zhang,Huanhuan Zhu,Tianqi Wang,Jingru Cui,Huahui Zeng,Xiangxiang Wu,Zhenqiang Zhang
Triptolide (TP) is a promising anti-tumor candidate derived from the herb Tripterygium wilfordii , but its poor water solubility and multi-organ toxicity limit its application. Here, we developed novel nanoparticles (TP-SP@NPs) modified with dextran sulfate and RGD peptide for double-targeted delivery of TP to both tumor cells and pro-tumor macrophages in pancreatic cancer treatment. TP-SP@NPs exhibited suitable particle size (about 98 nm), good stability and controlled release performance. TP-SP@NPs showed high cellular uptake in Pan02 cells and M2 macrophages through α v β 3 integrin-RGD interaction and SR-A-DS interaction, effectively inhibiting tumor growth by triggering apoptosis of these cells. In Pan02 tumor-bearing mice, TP-SP@NPs specifically accumulated at the tumor site and efficiently decreased the number of M2 macrophages, thereby exerting better curative effect on pancreatic cancer and lower systemic toxicity as compared with TP. As a result, TP-SP@NPs had achieved selective anti-tumor effect, good biosafety and great promise in clinical application.
研究领域:
药学
·
肿瘤学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2018
·Vol. 42
·期 14
·11565-11572
·
IF 3.201
Tao Wang,Guorong Jia,Chao Cheng,Qiuhu Wang,Xiao Li,Yanyan Liu,Chaofan He,Luguang Chen,Gaofeng Sun,Changjing Zuo
Multimodal imaging can improve the accuracy of cancer diagnosis by combining two or more imaging modalities into one system. In this study, PEGylated BaGdF5 nanoparticles (NPs) were synthesized by a hydrothermal method, and the formed PEG-BaGdF5 NPs showed good X-ray attenuation properties and positive MR contrast effects in vitro. Considering that the overexpression of integrin αvβ3 in the endothelial cells of angiogenic tumor vasculature is universal, RGD peptide, which can recognize and bind integrin αvβ3 specifically, was connected to the surface of PEG-BaGdF5 NPs. The resulting RGD-PEG-BaGdF5 NPs had good biocompatibility and a long half-life in vivo. In VX2 tumor-bearing mice, the HU values and MR signal enhancement of tumor sites in the targeted group were both higher than that in the non-targeted group after intravenous injection of RGD-PEG-BaGdF5 NPs or PEG-BaGdF5 NPs, respectively. Therefore, the RGD-PEG-BaGdF5 NPs may be used as dual-modal CT/MR contrast agents of different types of solid tumors via an active RGD-mediated vasculature targeting pathway.
研究领域:
医学影像
·
纳米技术
·
肿瘤学
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 30
·6338-6346
·
IF 4.726
Hao Hu,Yuanyuan You,Lizhen He,Tianfeng Chen
Angiogenesis is essential for tumorous progression and metastasis. The RGD (Arg–Gly–Asp acid) peptide has been demonstrated to be a remarkable targeting reagent and can be distinguished by the integrin receptor overexpressed in various human tumor cells. Mesoporous silica nanoparticles (MSNs) are one of the most promising carriers applied for delivery of drugs or genes. It is well known that NAMI-A is an excellent drug for antimigration of tumor cells. Targeting the tumor vasculature with RGD-modified nanomaterials is expected to be a promising strategy for cancer therapy. Herein we have investigated the antiangiogenic activity of NAMI-A-loaded and RGD peptide surface decorated mesoporous silica nanoparticles in vitro and in vivo. The results revealed that NAMI-A@MSN-RGD remarkably enhanced the cellular uptake and antiangiogenic efficacy in contrast to bare NAMI-A in vitro. The nanosystem of NAMI-A@MSN-RGD also exhibited inspiring antiangiogenic action in vivo. Furthermore, the RGD-functionalized nanodrug inhibited angiogenesis by means of apoptosis by triggering ROS-mediated DNA damage in human umbilical vein endothelial cells (HUVECs). Our results suggested that the use of RGD-peptide modified MSNs as a vehicle of anticancer drugs is an efficient way to construct cancer-targeted nanosystems with antiangiogenic activity.
研究领域:
药学
·
纳米医学
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2024
·Vol. 86
·期 1
·e70043
·
IF 3.5
Qingqing Li,Yufeng Liu,Yilin Cheng,Huaibao Cao,Kunda Du,Tianyu Zhu,Defeng Xu,Hang Hu
Poor selectivity to tumor cells is a major drawback in the clinical application of the antitumor drug docetaxel (DTX). Peptide–drug conjugates (PDCs) constructed by modifying antitumor drugs with peptide ligands that have high affinity to certain overexpressed receptors in tumor cells are increasingly assessed for their possibility of tumor-selective drug delivery. In the present research, DTX is condensed with 3-(pyridin-2-yldisulfanyl) propanoic acid via ester bond to obtain the intermediate Py-SS-DTX. Two conjugates GSS-DTX and RGDC-SS-DTX were obtained by conjugation of Py-SS-DTX with glutathione (GSH) and RGDC peptide through a thiol-disulfide exchange reaction. Afterwards, these two peptide–DTX conjugates were characterized by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. The GSS-DTX and RGDC-SS-DTX were further evaluated in terms of drug release, cell cycle inhibition, cell apoptosis, and cytotoxicity. The results show that both the GSS-DTX and RGDC-SS-DTX exhibit reduction-responsive drug release and RGDC-SS-DTX exhibit higher reduction-responsiveness. The in vitro antitumor activity study shows that RGDC-SS-DTX exhibits enhanced G2/M phase arrest, cell apoptosis rate, and cytotoxicity as compared to GSS-DTX and free DTX. Besides, RGDC-SS-DTX shows reduced cytotoxicity on normal cells as compared to free DTX. The RGDC-SS-DTX synthesized in this study represents a novel DTX conjugate to effectively and selectively inhibit tumor cells.
研究领域:
药学
·
肿瘤学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2018
·
IF 2.829
Boyi Niu,Yixian Zhou,Ting Wen,Guilan Quan,Vikramjeet Singh,Xin Pan,Chuanbin Wu
Packaging enough genetic materials is necessary for gene delivery, but functional modification of the carriers may affect their gene loading capacity. In this study, RGD peptide-modified mesoporous silica nanoparticles were synthesized to investigate the influences of functionalization on their DNA adsorption and desorption behaviors. Effects of the functionalization degree of the nanocarriers and the adsorption conditions including DNA concentration, pH, ionic strength and temperature were studied. The DNA adsorption of the nanocarriers were enhanced by reducing pH or adding moderate amounts of ionic salt. Compared with nonfunctional nanoparticles, nanoparticles with low degree of functionalization possessed decreased DNA adsorption capacity but increased adsorption stability. High degree of functionalization resulted in both poor adsorption capacity and stability. Systematic studies showed that the adsorption processes were spontaneous and endothermic, and could be well described by pseudo-second-order kinetic model , Langmuir and Freundlich models. In summary, the DNA loading capacity of mesoporous silica nanoparticles can be improved by proper functionalization and optimized adsorption conditions.
研究领域:
生物材料学
·
分子生物学
·
纳米医学
✓ 已验证
产品关联
DOI
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
危险品化学品经营许可证（带存储）