Vascular-homing peptides for cancer therapy

Lü, Lei; Qi, Huan; Zhu, Jie; Sun, Wen Xia; Zhang, Bin; Tang, Cheng-Wei; Cheng, Qiang

doi:10.1016/j.biopha.2017.05.054

Cited by 30 publications

(18 citation statements)

References 119 publications

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“…A considerable range of often linear tumor-homing peptides is documented in the literature, with a subset demonstrating in vivo imaging (30,31). However, to date the most prominent and effective examples of imaging peptides in clinical development or practice (e.g., somatostatin analogues) are derived from naturally occurring precedents often presented in a cyclic format, suggesting that the options available for the discovery and development of clinically attractive peptidic targeting agents remain limited (32,33).…”

Section: Discussionmentioning

confidence: 99%

Bicyclic Peptides as a New Modality for Imaging and Targeting of Proteins Overexpressed by Tumors

et al. 2019

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Molecular imaging of cancers using probes specific for tumor-associated target proteins offers a powerful solution for providing information regarding selection of targeted therapy, patient stratification, and response to therapy. Here we demonstrate the power of bicyclic peptides as targeting probes, exemplified with the tumor-overexpressed matrix metalloproteinase MT1-MMP as a target. A bicyclic peptide with subnanomolar affinity towards MT1-MMP was identified, and its radioconjugate showed selective tumor uptake in an HT1080 xenograft mouse model. Proteolytic stabilization of the peptide by chemical modification significantly enhanced the in vivo tumor signal [from 2.5%ID/g to 12%ID/g at 1 hour post injection (p.i.)]. Studies using mouse xenograft models with different cell lines show a robust correlation between tumor signals and in vivo MT1-MMP expression levels. Fatty acid modification of the bicy-clic peptide extended its circulating half-life, resulting in increased tumor signals (36%ID/g at 6 hours p.i.). Comparative work with an equipotent radiolabeled MT1-MMP targeting antibody demonstrated starkly differential biodistribution and tumor accumulation properties, with the tumor signal slowly increasing to 6.2%ID/g within 48 hours. The rapid tumor penetration characteristics of bicyclic peptides, coupled with high potency and chemical versatility, thus offer high-contrast imaging probes for clinical diagnostics with compelling additional potential in targeted therapy.Significance: This work demonstrates the potential of bicyclic peptides as a platform for the development of highcontrast imaging probes for potential use in clinical cancer diagnostics and molecularly targeted therapeutics.

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Section: Discussionmentioning

confidence: 99%

Bicyclic Peptides as a New Modality for Imaging and Targeting of Proteins Overexpressed by Tumors

et al. 2019

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“…For example, αVβ3-specific Arg–Gly–Asp-based cyclic peptides targeting the tumor vasculature or tumor cells have been successfully used to deliver therapeutic compounds, as well as image tumor lesions (theranostics) [185,186]. In general, these approaches have demonstrated superior ability in increasing drug uptake and activities in the tumors (reviewed in [185,187,188,189,190]). Dual targeting has further significantly improved drug delivery and activity.…”

Section: Targeting Integrins In Cancermentioning

confidence: 99%

Are Integrins Still Practicable Targets for Anti-Cancer Therapy?

Alday-Parejo

Stupp

Rüegg

2019

Cancers

135

127

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Correlative clinical evidence and experimental observations indicate that integrin adhesion receptors, in particular those of the αV family, are relevant to cancer cell features, including proliferation, survival, migration, invasion, and metastasis. In addition, integrins promote events in the tumor microenvironment that are critical for tumor progression and metastasis, including tumor angiogenesis, matrix remodeling, and the recruitment of immune and inflammatory cells. In spite of compelling preclinical results demonstrating that the inhibition of integrin αVβ3/αVβ5 and α5β1 has therapeutic potential, clinical trials with integrin inhibitors targeting those integrins have repeatedly failed to demonstrate therapeutic benefits in cancer patients. Here, we review emerging integrin functions and their proposed contribution to tumor progression, discuss preclinical evidence of therapeutic significance, revisit clinical trial results, and consider alternative approaches for their therapeutic targeting in oncology, including targeting integrins in the other cells of the tumor microenvironment, e.g., cancer-associated fibroblasts and immune/inflammatory cells. We conclude that integrins remain a valid target for cancer therapy; however, agents with better pharmacological properties, alternative models for their preclinical evaluation, and innovative combination strategies for clinical testing (e.g., together with immuno-oncology agents) are needed.

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“…RGR has been exploited as a carrier for delivery of therapeutic proteins (TNFα and IFNγ) to targeted sites in cancer therapy. 104 Another peptide that is targeting to angiogenic vasculature is F3. F3 (KDEPQRRSARLSAKPAPPKPEPKPKKAP AKK) is a 31-amino acid peptide that is able to target blood vessels and tumor tissue.…”

Section: Peptides-targeting Tumor Vasculaturementioning

confidence: 99%

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

Kebebe¹,

Liu²,

Wu³

et al. 2018

IJN

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Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents.

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Vascular-homing peptides for cancer therapy

Cited by 30 publications

References 119 publications

Bicyclic Peptides as a New Modality for Imaging and Targeting of Proteins Overexpressed by Tumors

Bicyclic Peptides as a New Modality for Imaging and Targeting of Proteins Overexpressed by Tumors

Are Integrins Still Practicable Targets for Anti-Cancer Therapy?

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

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