High-yield expression, purification and characterization of tumor-targeted IFN-α2a

Meng, Jing; Zhang, Yan; Wu, Jiaming; Li, L.; Xue, Xiaochang; Li, M.; Li, Wenhao; Hao, Qiang; Wan, Yi; Xin, Qin; Zhang, C.; You, Yanjie; Han, Wei; Zhang, Y.

doi:10.1080/14653240601094322

Cited by 31 publications

(23 citation statements)

References 17 publications

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“…Peptide-based radiopharmaceuticals can be produced easily and inexpensively and have many favorable properties, including fast clearance, rapid tissue penetration, and low antigenicity [6, 9, 15–17]. In this study, the cysteine beside NGR motif formed a cyclic via a disulfide linkage and the direct labeling method resulted in a very stable product.…”

Section: Discussionmentioning

confidence: 93%

Biodistribution and SPECT Imaging Study of^99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma

Wang

Yang

et al. 2014

BioMed Research International

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A peptide containing Asn-Gly-Arg(NGR) sequence was synthesized and directly labeled with 99mTc. Its radiochemical characteristics, biodistribution, and SPECT imaging were evaluated in nude mice bearing human HepG2 hepatoma. Nude mice bearing HepG2 were randomly divided into 5 groups with 5 mice in each group and injected with ~7.4 MBq 99mTc-NGR. The SPECT images were acquired in 1, 4, 8, and 12 h postinjection via caudal vein. The metabolism of tracers was determined in major organs at different time points, which demonstrated rapid, significant tumor uptake and slow tumor washout. The control group mice were blocked by coinjecting unlabelled NGR (20 mg/kg). Tumor uptake was (2.52 ± 0.83%) ID/g at 1 h, with the highest uptake of (3.26 ± 0.63%) ID/g at 8 h. In comparison, the uptake of the blocked control group was (1.65 ± 0.61%) ID/g at 1 h after injection. The SPECT static images and the tumor/muscle (T/NT) value were obtained. The highest T/NT value was 7.58 ± 1.92 at 8 h. The xenografted tumor became visible at 1 h and the clearest image of the tumor was observed at 8 h. In conclusion, 99mTc-NGR can be efficiently prepared and it exhibited good properties for the potential SPECT imaging agent of tumor.

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Section: Discussionmentioning

confidence: 93%

Biodistribution and SPECT Imaging Study of^99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma

Wang

Yang

et al. 2014

BioMed Research International

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“…The biologic activity of other cytokines and antiangiogenic molecules, such as IFN␥, IFN␣2a, endostatin and tumstatin fragment have been improved by coupling to NGR peptides. [41][42][43]52 Targeted delivery of minute amounts (picogram dose range) of a recombinant IFN␥-CNGRC conjugate (IFN␥-NGR) to tumor vasculature overcomes major counter regulatory mechanisms and delays tumor growth in mice. 40 NGR peptides have been used also for gene therapy.…”

Section: Use Of Ngr Peptides For Targeted Delivery Of Drugs and Partimentioning

confidence: 99%

The neovasculature homing motif NGR: more than meets the eye

Corti

Curnis

Arap

et al. 2008

Blood

176

169

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IntroductionPhage display libraries are often used for discovering peptide sequences that interact with proteins differentially expressed in normal and pathologic tissues. 1,2 Indeed, in vivo panning of peptide-phage libraries in tumor-bearing animal models has proven useful for selecting peptides able to interact with proteins expressed within tumor-associated blood vessels and therefore to home to neoplastic tissues. 3 Among the ligands identified so far, cyclic and linear peptides containing the Asn-Gly-Arg (NGR) motif have been exploited for systemic, yet ligand-directed targeted delivery of therapeutic and imaging agents to angiogenic blood vessels, including cytotoxic drugs and cytokines, among other entities (such as viruses and nanoparticles). These findings highlight the value of NGR peptides in drug development. In this review we discuss the biochemical and biologic properties of NGR and NGR-derived compounds. Given that many native proteins contain the sequence NGR, we also address the emerging role of NGR as an unrecognized "molecular timer" due to the timedependent generation of isoAsp-Gly-Arg (isoDGR), a new integrinbinding motif that regulates a gain-of-function within the extracellular matrix protein fibronectin. 4 The discovery of the NGR motifIn vitro panning of several phage libraries against the ␣5␤1 integrin led to the selection of various RGD-containing peptides and also of the peptide NGRAHA. 5 These peptides (including NGRHA) inhibited cell attachment mediated by both ␣v␤3 and ␣v␤5 integrins. Moreover, 8 NGR-containing peptides were isolated upon screening of cyclic peptide libraries under similar experimental conditions. 6 Notably, one selected phage clone displayed the peptide CVLNGRMEC, which is similar to the sequence ALN-GREE found within the 9th type III repeat of human fibronectin. 7 Further studies based on in vitro selection of libraries on ␣v␤3, revealed several different peptides containing the NGR motif, such as NGRIPD, TNGRGP, NGRSFR, RSRNGR, NGRNTV. 8 In another line of investigation, in vivo phage-display screenings were performed to isolate tumor-homing peptides. Systemic administration of a phage library into nude mice bearing human breast carcinoma xenografts led to selection of a tumor vasculaturehoming phage carrying the sequence CNGRCVSGCAGRC. 3 Tumor homing was inhibited by co-injection with the CNGRC peptide (NGR-2C) indicating that this short cyclic loop is a functional tumor targeting peptide. Phage displaying the peptides NGRAHA or CVLNGRMEC, previously identified in vitro, also selectively localized to tumors. 3 The NGR receptor(s)In vivo phage display-based studies showed that also the peptide ACDCRGDCFC (RGD-4C), an ␣v␤3/␣v␤5 binding sequence, can bind to tumor neovasculature. 3,9 Cross-inhibition experiments of NGR-2C and RGD-4C-phage clones with synthetic RGD-4C and NGR-2C peptides showed that RGD-4C peptide does not compete the homing of NGR-2C-phage to tumors and vice versa. 3 This result suggests that NGR-2C and RGD-4C bind to distinct receptors in tumor ...

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“…Other cytokines and anti-angiogenic/anti-vascular polypeptides have been coupled to NGR to improve their activity, including IFNalpha2a [15,71], endostatin [18,72] and a tumstatin fragment 35-135 [16]. Interestingly, human endostatin has an internal NGR sequence, which is not accessible to CD13.…”

Section: Ngr-peptide Conjugates With Cytokines Anti-angiogenic and Vmentioning

confidence: 97%

“…For instance, peptides containing cyclic CNGRC and linear GNGRG motives have been used for delivering tumor necrosis factor alpha (TNF) [6][7][8], interferon gamma [9][10][11], and liposomal doxorubicin [12,13] to tumor neovasculature, improving their therapeutic properties. Other investigators have used the NGR motif embedded in similar or different molecular scaffolds for delivering chemotherapeutic drugs, antiangiogenic drugs, tissue factor, viruses and other compounds to tumor vessels [4,[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Tumor Vasculature Targeting Through NGR Peptide-Based Drug Delivery Systems

Corti

Curnis

2011

CPB

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Various peptide sequences have been discovered by selecting peptide-phage display libraries in vitro against specific receptors or in vivo in tumor-bearing animals. One class of these peptides is characterized by the presence of Asn-Gly-Asp (NGR), a structural motif that can recognize the endothelium and other cells of neoangiogenic vessels. Because of this property these peptides have been used by several investigators to deliver a variety of drugs, cytokines, nanoparticles, viruses and imaging agents to tumor blood vessels. Here we review the reports on these conjugates and discuss the structural, functional and stability properties of NGR embedded into different molecular scaffolds.

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High-yield expression, purification and characterization of tumor-targeted IFN-α2a

Cited by 31 publications

References 17 publications

Biodistribution and SPECT Imaging Study of^99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma

Biodistribution and SPECT Imaging Study of^99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma

The neovasculature homing motif NGR: more than meets the eye

Tumor Vasculature Targeting Through NGR Peptide-Based Drug Delivery Systems

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High-yield expression, purification and characterization of tumor-targeted IFN-α2a

Cited by 31 publications

References 17 publications

Biodistribution and SPECT Imaging Study of99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma

Biodistribution and SPECT Imaging Study of99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma

The neovasculature homing motif NGR: more than meets the eye

Tumor Vasculature Targeting Through NGR Peptide-Based Drug Delivery Systems

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Product

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Biodistribution and SPECT Imaging Study of^99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma

Biodistribution and SPECT Imaging Study of^99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma