Integrin α<sub>v</sub>β<sub>3</sub>‐targeted cancer therapy

Liu, Zhaofei; Wang, Fan; Chen, Xiaoyuan

doi:10.1002/ddr.20265

Cited by 271 publications

(226 citation statements)

References 82 publications

(86 reference statements)

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“…For example, v3-integrin, an integrin overexpressed in the tumor vascular endothelium, has an important role in angiogenesis and tumor growth (Brooks et al, 1995;Eliceiri and Cheresh, 2000;Friedlander et al, 1996;Kumar, 2003). RGDcontaining peptides with a variable degree of affinity and selectivity for this integrin have been developed and used for delivering a variety of drugs and nanoparticles to tumor vessels (Desgrosellier and Cheresh, 2009;Liu et al, 2008;Ruoslahti et al, 2010). Given the structural and functional similarities between RGD and isoDGR it is conceivable that peptides containing the isoDGR motif could also be exploited as specific ligands for the targeted delivery of drugs, imaging agents or other compounds to tumors.…”

Section: Pharmacological Implications and Therapeutic Opportunities Fmentioning

confidence: 99%

“…The isoDGR motif might also be exploited, similar to RGD, for the generation of integrin antagonists, which are currently being investigated for the treatment of cancer, osteoporosis and coagulation disorders (Desgrosellier and Cheresh, 2009;Liu et al, 2008). For example, c(RGDf[NMe]V) (also known as Cilengitide) is a cyclic RGD-peptide that binds v3-and v5-integrins and inhibits angiogenesis.…”

Section: Pharmacological Implications and Therapeutic Opportunities Fmentioning

confidence: 99%

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Isoaspartate-dependent molecular switches for integrin–ligand recognition

Corti¹,

Curnis²

2011

Journal of Cell Science

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Formation of isoAsp in ECM proteins and its functional effects Formation of isoAsp and ECM protein damageThe formation of isoAsp residues at Asn or Asp residues in proteins is generally considered a degradation reaction as a consequence of protein aging. IsoAsp formation has been shown to occur in ECM proteins, including collagen types I and III, in fibronectin, in -crystallin and in the ECM of the mammalian brain (Lanthier and Desrosiers, 2004;Lindner and Helliger, 2001; Reissner and Aswad, SummaryIntegrins are cell-adhesion receptors that mediate cell-extracellular-matrix (ECM) and cell-cell interactions by recognizing specific ligands. Recent studies have shown that the formation of isoaspartyl residues (isoAsp) in integrin ligands by asparagine deamidation or aspartate isomerization could represent a mechanism for the regulation of integrin-ligand recognition. This spontaneous posttranslational modification, which might occur in aged proteins of the ECM, changes the length of the peptide bond and, in the case of asparagine, also of the charge. Although these changes typically have negative effects on protein function, recent studies suggested that isoAsp formation at certain Asn-Gly-Arg (NGR) sites in ECM proteins have a gain-of-function effect, because the resulting isoAsp-Gly-Arg (isoDGR) sequence can mimic Arg-Gly-Asp (RGD), a well-known integrin-binding motif. Substantial experimental evidence suggests that the NGR-to-isoDGR transition can occur in vitro in natural proteins and in drugs containing this motif, thereby promoting integrin recognition and cell adhesion. In this Commentary, we review these studies and discuss the potential effects that isoAsp formation at NGR, DGR and RGD sites might have in the recognition of integrins by natural ligands and by drugs that contain these motifs, as well as their potential biological and pharmacological implications.

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Section: Pharmacological Implications and Therapeutic Opportunities Fmentioning

confidence: 99%

Section: Pharmacological Implications and Therapeutic Opportunities Fmentioning

confidence: 99%

Isoaspartate-dependent molecular switches for integrin–ligand recognition

Corti¹,

Curnis²

2011

Journal of Cell Science

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“…Targeting of the tumor neovasculature can also be accomplished by exploiting the overexpression of the a v b 3 integrin [96,97]. Importantly, the a v b 3 integrin is also overexpressed by several types of cancer cells as in breast and brain tumors.…”

Section: Photosensitizers Conjugated To Peptidesmentioning

confidence: 99%

Strategies for optimizing the delivery to tumors of macrocyclic photosensitizers used in photodynamic therapy (PDT)

Moret

Reddi

2017

J. Porphyrins Phthalocyanines

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This review briefly summaries the principles and mechanisms of action of photodynamic therapy (PDT) as concerns its application in the oncological field, highlighting its drawbacks and some of the strategies that have been or are being explored to overcome them. The major aim is to increase the efficiency and selectivity of the photosensitizer (PS) uptake in the cancer cells for optimizing the PDT effects on tumors while sparing normal cells. Some attempts to achieve this are based on the conjugation of the PS to biomolecules (small ligands, peptides) functioning as carriers with the ability to efficiently penetrate cells and/or specifically recognize and bind proteins/receptors overexpressed on the surface of cancer cells. Alternatively, the PS can be entrapped in nanocarriers derived from various types of materials that can target the tumor by exploiting the enhanced permeability and retention (EPR) effects. The use of nanocarriers is particularly attractive because it allows the simultaneous delivery of more than one drug with the possibility of combining PDT with other therapeutic modalities.

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“…[47] Similarly, nanoparticles have also been conjugated with RGD (Arg-Gly-Asp) peptides due to their high affinity to αvβ3 integrin receptors that are highly expressed in tumor cells, thus enhancing the intratumoral drug delivery. [48] Aptamers are small oligonucleotides that can be selected to bind tightly and specifically to a target molecule, are also widely applied into nanoparticle formation besides the surface modification. Doxorubicin can efficiently intercalate into DNA aptamer structure without affecting the aptamer's three-dimensional structure.…”

Section: Second Generation Nanomedicinesmentioning

confidence: 99%

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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Explosive growth of nanomedicines continues to significantly impact the therapeutic strategies for effective cancer treatment. Despite the significant progress in the development of advanced nanomedicines, successful clinical translation remains challenging. As cancer nanomedicine is a multidisciplinary field, the fundamental problem is that the knowledge gaps stem from different vantage points in the understanding of cancer nanomedicines. The complexities and heterogenecity of both nanomedicines and cancer are further demanding the integration of highly diverse expertise to develop clinically translatable cancer nanomedicines. This progress report aims to discuss the current understanding of cancer nanomedicines between different research areas in terms of nanoparticle engineering, formulation, tumor patho-physiology and clinical medicine, as well as to identify the knowledge gaps lying at the interface between the different fields of research in nanomedicine. Here we also highlight for the necessity to harmonize the multidisciplinary effort in the research of nanomedicines in order to bridge the knowledge and to advance the full understanding in cancer nanomedicines. A paradigm shift is needed in the strategic development of disease specific nanomedicines in order to foster the successful translation into clinic of future cancer nanomedicines.

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Integrin α_vβ₃‐targeted cancer therapy

Abstract: Anti-angiogenesis is a promising strategy for the treatment of cancer. Integrins, consisting of two noncovalently bound transmembrane α and β subunits, are an important molecular family involved in tumor angiogenesis.

Cited by 271 publications

References 82 publications

Isoaspartate-dependent molecular switches for integrin–ligand recognition

Isoaspartate-dependent molecular switches for integrin–ligand recognition

Strategies for optimizing the delivery to tumors of macrocyclic photosensitizers used in photodynamic therapy (PDT)

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

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Integrin αvβ3‐targeted cancer therapy

Abstract: Anti-angiogenesis is a promising strategy for the treatment of cancer. Integrins, consisting of two noncovalently bound transmembrane α and β subunits, are an important molecular family involved in tumor angiogenesis.

Cited by 271 publications

References 82 publications

Isoaspartate-dependent molecular switches for integrin–ligand recognition

Isoaspartate-dependent molecular switches for integrin–ligand recognition

Strategies for optimizing the delivery to tumors of macrocyclic photosensitizers used in photodynamic therapy (PDT)

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Contact Info

Product

Resources

About

Integrin α_vβ₃‐targeted cancer therapy