Tumor penetrability and anti-angiogenesis using iRGD-mediated delivery of doxorubicin-polymer conjugates

Wang, Ke; Zhang, Xiaofeng; Liu, Yang; Liu, Chang; Jiang, Baohong; Jiang, Yanyan

doi:10.1016/j.biomaterials.2014.06.042

Cited by 163 publications

(133 citation statements)

References 32 publications

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“…The further quantitative analysis showed that the administration of Ta1-iRGD decreased CD31-positive areas within the tumor by 33 % and Ta1 only by 7 %. Consistent with these results, the adding of iRGD to doxorubicin, a well-known anticancer drug, can significantly down-regulated the vascular density and diameter compared with control group [37].These results also partly explained the reason that Ta1-iRGD showed better effect on tumor inhibition than Ta1.…”

Section: Ta1-irgd Decreased Vascular Structures In the Tumor Tissuessupporting

confidence: 78%

A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects

Lao

et al. 2015

Apoptosis

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Thymosin alpha 1 (Tα1) is commonly used for treating several diseases; however its usage has been limited because of poor penetration of the target tissue, such as tumor cells. In the present study, Tα1-iRGD, a peptide by conjugating Tα1 with the iRGD fragment, was evaluated its performance in MCF-7 and MDA-MB-231 human breast cancer cells. Compared with the wild-type peptide, Tα1-iRGD was more selective in binding tumor cells in the cell attachment assay. Furthermore, the MTT assay confirmed that Tα1-iRGD proved more effective in significantly inhibiting the growth of MCF-7 cells in contrast to the general inhibition displayed by Tα1. Further, conjugation of Tα1 with iRGD preserved the immunomodulatory activity of the drug by increasing the proliferation of mouse spleen lymphocytes. Further, compared with Tα1 treatment, Tα1-iRGD treatment of MCF-7 cells considerably increased the number of cells undergoing apoptosis, resulting in a dose-dependent inhibition of cancer cell growth, which was associated with a much better effect on up-regulation of the expression of BCL2-associated X protein (Bax), caspase 9, etc. More importantly, treatment with Ta1-iRGD was more efficacious than treatment with Ta1 in vivo. This study highlights the importance of iRGD on enhancement of cell penetration and tumor accumulation. In summary, our findings demonstrate that the novel modified Tα1 developed in this study has the potential to be used for treating breast cancer.

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Section: Ta1-irgd Decreased Vascular Structures In the Tumor Tissuessupporting

confidence: 78%

A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects

Lao

et al. 2015

Apoptosis

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“…Compared with conventional RGDyC cyclic peptides, iRGD-mediated polymer-drug conjugates could significantly improve the efficacy of tumor therapy through enhancing tumor accumulation and penetration. For instance, Jiang et al conjugated doxorubicin (DOX) to PEG-PAMAM via an acid-sensitive cis-aconityl linkage, and then respectively modified the conjugates with RGDyC and iRGD [51]. In vitro C6 glioma spheroid penetration study showed that iRGD-targeted conjugates had a stronger penetrating ability with a penetration depth of 144 mm relative to RGDyC-mediated conjugates (115 mm).…”

Section: Peptide-targeted Polymer-drug Conjugatesmentioning

confidence: 97%

Targeted polymer-drug conjugates: Current progress and future perspective

Yang

et al. 2015

Colloids and Surfaces B: Biointerfaces

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“…With better tumor penetrability, DOX/DAs were easier to get into the deep area of tumor tissues and obtain an enhanced antitumor efficiency. 38 …”

Section: Uptake Study and Cytotoxicity Of Dox-loaded Npsmentioning

confidence: 99%

Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin

Chen¹,

Li²,

Tang³

et al. 2017

IJN

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Physicochemical properties, including particle size, zeta potential, and drug release behavior, affect targeting efficiency, cellular uptake, and antitumor effect of nanocarriers in a formulated drug-delivery system. In this study, a novel stepwise pH-responsive nanodrug delivery system was developed to efficiently deliver and significantly promote the therapeutic effect of doxorubicin (DOX). The system comprised dimethylmaleic acid-chitosan-urocanic acid and elicited stepwise responses to extracellular and intracellular pH. The nanoparticles (NPs), which possessed negative surface charge under physiological conditions and an appropriate nanosize, exhibited advantageous stability during blood circulation and enhanced accumulation in tumor sites via enhanced permeability and retention effect. The tumor cellular uptake of DOX-loaded NPs was significantly promoted by the first-step pH response, wherein surface charge reversion of NPs from negative to positive was triggered by the slightly acidic tumor extracellular environment. After internalization into tumor cells, the second-step pH response in endo/lysosome acidic environment elicited the on-demand intracellular release of DOX from NPs, thereby increasing cytotoxicity against tumor cells. Furthermore, stepwise pH-responsive NPs showed enhanced antiproliferation effect and reduced systemic side effect in vivo. Hence, the stepwise pH-responsive NPs provide a promising strategy for efficient delivery of antitumor agents.

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Tumor penetrability and anti-angiogenesis using iRGD-mediated delivery of doxorubicin-polymer conjugates

Cited by 163 publications

References 32 publications

A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects

A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects

Targeted polymer-drug conjugates: Current progress and future perspective

Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin

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