Cell penetrating peptides improve tumor delivery of cargos through neuropilin-1-dependent extravasation

Kadonosono, Tetsuya; Yamano, Akihiro; Goto, Toshiki; Tsubaki, Takuya; Niibori, Mizuho; Kuchimaru, Takahiro; Kizaka‐Kondoh, Shinae

doi:10.1016/j.jconrel.2015.01.011

Cited by 50 publications

(41 citation statements)

References 32 publications

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“…Kadonosono et al found that cell penetrating peptides fused to fluorescent proteins had reduced accumulation in tumors (about 50%) of mice that had received a prior injection of an antibody to NRP1 (23). Interestingly, no increase in vascular permeability was observed with these cell penetrating peptides in vivo , suggesting that these peptides were able to bind NRP1 without activating NRP1-transport pathways.…”

Section: Tumor-penetrating Peptidesmentioning

confidence: 99%

NRP1 transport of cancer therapeutics mediated by tumor-penetrating peptides

Leng¹,

Woodle²,

Mixson³

2017

Drugs of the Future

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Summary Whereas uptake of low molecular weight agents is generally inhibited in tumors due to high interstitial pressure, tumor uptake of macromolecules is increased due to enhanced permeability and retention (EPR). Small molecule drugs alone or incorporated in nanoparticles (NP) have largely been dependent on such physical tumor uptake (passive) for therapeutic activity. Although passive targeted NP such as Stealth Liposomal Doxorubicin (Doxil ®) are effective with improved safety, drug delivery to tumors is still significantly limited. To improve tumor delivery and efficacy, tumor-penetrating peptides (TPP), which contain sequences that target the tumor and activate the neuropilin-1 receptor (NRP1), have either been co-administered with or conjugated to both small and large therapeutic molecules. In this review, we will discuss TPP-mediated therapeutics which target the NRP1 transport system of tumors.

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Section: Tumor-penetrating Peptidesmentioning

confidence: 99%

NRP1 transport of cancer therapeutics mediated by tumor-penetrating peptides

Leng¹,

Woodle²,

Mixson³

2017

Drugs of the Future

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“…The peptide is used to increase the pore diameter and surface area of tumor blood vessels, and to reduce the pressure effect in the tumor interstitium, increasing the rate of diffusion of small molecule drugs (10)(11)(12). The scientific interest in iRGD has resulted from its binding to NRP-1 in particular, as this triggers extravasation (13). Furthermore, iRGD specifically penetrates into angiogenic vessels and tumor tissues.…”

Section: Introductionmentioning

confidence: 99%

iRGD as a tumor-penetrating peptide for cancer therapy

Yin

Zhang

Yang

et al. 2017

Molecular Medicine Reports

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As a tumor-targeting and ‑penetrating peptide, iRGD binds to αv integrins and neuropilin‑1 receptors, which are expressed at high levels on tumor cells and the surfaces of vasculature. Subsequently, iRGD penetrates deep into the tumor parenchyma with antitumor drugs, imaging agents, immune modulators and biological products. These substances are either chemically linked to the peptide or co‑injected with the peptide. The iRGD peptide can be readily synthesized, exhibits significantly improved penetration, compared with traditional peptides, and can effectively inhibit tumor metastasis. Therefore, the peptide is now used widely for the diagnosis and treatment of cancer. However, whether the peptide is able to promote the entry of drugs into non‑targeted cells remains to be fully elucidated. In this review, an overview of iRGD is presented, focusing on its identification, mechanism of action and previous studies on its roles in various types of cancer. Studies in previous years have demonstrated the potential of the iRGD protein for tumors diagnosis and targeted treatment, which warrants further investigation.

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“…Neuropilin-1 (NRP1) and its homologue NRP2, expressed on the surface of several normal cell types including endothelial cells, are often overexpressed on malignant tumor cells [6,7]. NRP1 and 2 have been targeted to develop tumor penetration peptides as promoter agents [8,9]. Due to the structural similarities of their extracellular domains, NRP1 and NRP2 (NRP1/2) have many ligands in common, such as those belonging to Class III Semaphorin (Sema3) and vascular endothelial growth factor (VEGF) families [7].…”

Section: Introductionmentioning

confidence: 99%