BIOMATERIALS
·
2014
·
IF 8.312
Wantong Song,Zhaohui Tang,Dawei Zhang,Ying Zhang,Haiyang Yu,Mingqiang Li,Shixian Lv,Hai Sun,Mingxiao Deng,Xuesi Chen
There are two important obstacles for the currently applied anti-cancer drug delivery systems. One is the conflict between long-circulation and cellular uptake while the other one is the achievement of ideal anti-cancer efficacy. To solve these problems, we designed a polypeptide-based micelle system that combined the advantages of receptor mediated endocytosis and multi-drug delivery. Firstly, an amphiphilic PLG- g -Ve/PEG graft copolymer was prepared by grafting α-tocopherol (Ve) and polyethylene glycol (PEG) to poly( l -glutamic acid) (PLG). Then docetaxel (DTX) and cisplatin (CDDP) were co-loaded into the PLG- g -Ve/PEG micelles via hydrophobic and chelation effect. After that, the surface of the dual-drug-loaded micelles was decorated with an α v β 3 integrin targeting peptide c(RGDfK). The targeted dual-drug-loaded micelles showed synergistic cytotoxicity and enhanced internalization rate in mouse melanoma (B16F1) cells. In vivo tests demonstrated that remarkable long circulation, anti-tumor and anti-metastasis efficacy could be achieved using this drug delivery system. This work revealed a strategy for the design and preparation of anti-cancer drug delivery systems with reduced side effect, enhanced anti-tumor and anti-metastasis efficacy.
研究领域:
药学
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肿瘤学
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生物材料
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Renuka Khatik,Zhengyun Wang,Debo Zhi,Sonia Kiran,Pankaj Dwivedi,Gaolin Liang,Bensheng Qiu,Qing Yang
Multifunctional nanomaterials with targeted imaging and chemotherapy have high demand with great challenge. Herein, we rationally aimed to design multifunctional drug delivery systems by RGD-modified chitosan (CH)-coated nanoneedles (NDs) of gadolinium arsenate (RGD-CH-Gd-AsNDs). These NDs have multifunctionality for imaging and targeted therapy. NDs on intravenous administration demonstrated significant accumulation of As ions/species in tumor tissues, which was monitored by the change in T1-weighted magnetic resonance (MR) imaging. Moreover, NDs were well opsonized in cells with high specificity, subsequently inducing apoptosis to the HepG2 cells. Consequent to this, the in vivo results demonstrated biosafety, enhanced tumor targeting, and tumor regression in a subcutaneously transplanted xenograft model in nude mice. These RGD-CH-Gd-AsNDs have great potential, and we anticipate that they could serve as a novel platform for real-time T1-weighted MR diagnosis and chemotherapy.
研究领域:
医学影像学
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药物递送系统
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 54
·30887-30893
·
IF 2.936
Wen-Qiang Ding,Si-Yong Qin,Yin-Jia Cheng,Yi-Han Ma,Ai-Qing Zhang
Here we designed and constructed a tryptophan-phenylalanine-phenylalanine-tryptophan (WFFW) tetrapeptide, which generated photostable and tunable fluorescence emission signals from 340 nm to 500 nm. The WFFW tetrapeptide could self-assemble into a spherical nanostructure with enhanced fluorescence intensity. Driven by π–π stacking and hydrogen bond interaction, WFFW co-assembled with arginine-glycine-aspartic acid (RGD) modified WFFW to form a cancer-targeted fluorescent nanoprobe, which could selectively image the cancer cells.
研究领域:
生物化学
·
医学影像
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纳米医学
✓ 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
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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
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
MOLECULES
·
2023
·Vol. 28
·期 18
·6692
·
IF 4.6
Hongcai Wang,Ruhong Yin,Xiuqiong Chen,Ting Wu,Yanan Bu,Huiqiong Yan,Qiang Lin
To enhance the mechanical strength and cell adhesion of alginate hydrogel, making it satisfy the requirements of an ideal tissue engineering scaffold, the grafting of Arg-Gly-Asp (RGD) polypeptide sequence onto the alginate molecular chain was conducted by oxidation of sodium periodate and subsequent reduction amination of 2-methylpyridine borane complex (2-PBC) to synthesize alginate dialdehyde grafted RGD derivatives (ADA-RGD) with good cellular affinity. The interpenetrating network (IPN) composite hydrogels of alginate/polyvinyl alcohol/cellulose nanocrystals (ALG/PVA/CNCs) were fabricated through a physical mixture of ion cross-linking of sodium alginate (SA) with hydroxyapatite/D-glucono-δ-lactone (HAP/GDL), and physical cross-linking of polyvinyl alcohol (PVA) by a freezing/thawing method, using cellulose nanocrystals (CNCs) as the reinforcement agent. The effects of the addition of CNCs and different contents of PVA on the morphology, thermal stability, mechanical properties, swelling, biodegradability, and cell compatibility of the IPN composite hydrogels were investigated, and the effect of RGD grafting on the biological properties of the IPN composite hydrogels was also studied. The resultant IPN ALG/PVA/CNCs composite hydrogels exhibited good pore structure and regular 3D morphology, whose pore size and porosity could be regulated by adjusting PVA content and the addition of CNCs. By increasing the PVA content, the number of physical cross-linking points in PVA increased, resulting in greater stress support for the IPN composite hydrogels of ALG/PVA/CNCs and consequently improving their mechanical characteristics. The creation of the IPN ALG/PVA/CNCs composite hydrogels’ physical cross-linking network through intramolecular or intermolecular hydrogen bonding led to improved thermal resistance and reduced swelling and biodegradation rate. Conversely, the ADA-RGD/PVA/CNCs IPN composite hydrogels exhibited a quicker degradation rate, attributed to the elimination of ADA-RGD by alkali. The results of the in vitro cytocompatibility showed that ALG/0.5PVA/0.3%CNCs and ADA-RGD/PVA/0.3%CNCs composite hydrogels showed better proliferative activity in comparison with other composite hydrogels, while ALG/PVA/0.3%CNCs and ADA-RGD/PVA/0.3%CNCs composite hydrogels displayed obvious proliferation effects, indicating that PVA, CNCs, and ADA-RGD with good biocompatibility were conducive to cell proliferation and differentiation for the IPN composite hydrogels.Keywords:alginate;interpenetrating network composite hydrogels;cellular adhesion;cellular adhesion;tissue engineering
研究领域:
生物材料学
·
组织工程学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2022
·Vol. 12
·期 28
·18004-18011
·
IF 4.036
Lingling Xu,Chuan Zhou,Fan Wang,Huiqin Liu,Guangyuan Dong,Siyi Zhang,Tao Liu
In this study, a drug delivery system was prepared by grafting the targeting molecule arginine-glycine-aspartic acid (RGD) onto hyperbranched polyglycerol (HPG)-modified β-cyclodextrin (β-CD-HPG) for the targeted inhibition of nasopharyngeal carcinoma (NPC) cells. The obtained β-CD-HPG-RGD with a relatively small size and low surface charge delivered docetaxel (Doc) effectively and displayed a targeting effect to human NPC HNE-1 cells, as confirmed by confocal laser scanning microscopy and flow cytometry. The in vitro drug release analysis exhibited the controlled drug release kinetics of the β-CD-HPG-RGD/Doc nanomedicine. β-CD-HPG-RGD/Doc effectively inhibited the proliferation of HNE-1 cells and promoted apoptosis. Moreover, its biocompatibility in vitro and in vivo was assessed. The results indicate that the β-CD-HPG-RGD/Doc nanomedicine has potential application in NPC targeting therapy.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Huifang Nie,Rong Huang,Guangwei Jiang,Wenshuai Li,Lan Yang,Meng Zhang,Min Qian,Wei Guo,Tao Ye,Rongqin Huang
Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α v β 3 because of the multivalent interactions between larger active nanoparticles and integrin α v β 3 . In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.
研究领域:
肿瘤学
·
纳米医学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
Science Advances
·
2025
·Vol. 11
·期 39
·
IF 12.5
Taige Chen,Rui Liu,Qin Chen,Xuebing Feng,Bin Kong,Yuanjin Zhao
Dry eye disease (DED) is characterized by chronic inflammation and an unstable tear film. Stem cells have shown potential for DED treatment, but the main challenge lies in improving cell delivery effectiveness. Here, we developed eye drops for autoimmune DED treatment using porous arginine–glycine–aspartic acid (RGD)–modified alginate microcarriers with mesenchymal stem/stromal cells (MSCs) (RGD-Alg@MSCs). These microcarriers provided a favorable microenvironment for large-scale cell expansion while maintaining stemness with ideal mechanical properties for ocular application. In vitro, RGD-Alg@MSCs demonstrated significantly enhanced therapeutic effects compared to conventional MSCs, including improved cell viability, reduced apoptosis and reactive oxygen species, and enhanced release of immunomodulatory factors. Transcriptomic analysis revealed distinct molecular mechanisms underlying these enhanced therapeutic effects. In the mouse model, RGD-Alg@MSCs exhibited prolonged ocular retention and enhanced tear production, promoted corneal healing, and suppressed inflammation by inhibiting dendritic cell activation and T H 17 differentiation. Our microcarrier system substantially improves stem cell delivery efficiency for treating autoimmune DED.
研究领域:
眼科
·
免疫学
·
再生医学
·
药物递送
·
分子生物学
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2018
·
IF 4.244
Kai Dong,Yan Zhang,Lu Zhang,Zhenzhen Wang,Jinsong Ren,Xiaogang Qu
Nowadays, cancer has been one of the major threats to human beings throughout the world. Nanomedicines have been demonstrated as a promising candidate for cancer chemotherapy. In this work, we facilely constructed a RGD (Arg-Gly-Asp) modified [email protected] imidazolate framework-8 ( [email protected] @ZIF-8) as a novel metal-organic frameworks-based hydrophobic drug delivery system for targeted and enhanced cancer treatment. In our system, the nanoplatform exhibited the superior property of target to the cancer cells due to the function with RGD. More importantly, the [email protected] @ZIF-8 nanoplatform has shown the enhanced cancer cell treatment due to the excellent pH-responsive hydrophobic anticancer drug delivery and intracellular ROS generation. With the excellent targeting and enhanced therapy performance, we envision that the hydrophobic anticancer drug delivery system could become a potential therapeutic agent for targeted cancer treatment.
研究领域:
肿瘤学
·
药剂学
·
纳米生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Jiaojiao Wu,Xueyan Wei,Zhenguang Li,Haotian Chen,Rui Gao,Peng Ning,Yingze Li,Yu Cheng
Using mechanical cues for cancer cells can realize precise control and efficient therapeutic effects. However, the cell cycle-specific response for dynamic mechanical manipulation is barely investigated. Here, RGD-modified iron oxide nanomanipulators were utilized as the intracellular magneto-mechanical transducers to investigate the mechanical impacts on the cell cycle under a dynamic magnetic field for cancer treatment. The G2/M phase was identified to be sensitive to the intracellular magneto-mechanical modulation with a synergistic treatment effect between the pretreatment of cell cycle-specific drugs and the magneto-mechanical destruction, and thus could be an important mechanical-targeted phase for regulation of cancer cell death. Finally, combining the cell cycle-specific drugs with magneto-mechanical manipulation could significantly inhibit glioma and breast cancer growth in vivo . This intracellular mechanical stimulus showed cell cycle-dependent cytotoxicity and could be developed as a spatiotemporal therapeutic modality in combination with chemotherapy drugs for treating deep-seated tumors.
研究领域:
癌症生物学
·
纳米技术
·
生物医学工程
·
治疗学
✓ 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）