RGD-modified polymeric micelles as potential carriers for targeted delivery to integrin-overexpressing tumor vasculature and tumor cells

Wang, Yiguang; Wang, Xun; Zhang, Yifei; Yang, Shijin; Wang, Jiancheng; Zhang, Xuan; Zhang, Qiang

doi:10.1080/10611860902974085

Cited by 41 publications

(23 citation statements)

References 37 publications

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“…The vitronectin-binding-receptor αvβ3 and αvβ5 integrins have higher expression levels in metastatic breast cancer cells, angiogenic tumor endothelial cells, and malignant tumor cells [32,33], indicating a crucial role of these integrins in breast malignancy. Integrin αvβ3 is involved in regulating migration of malignant cells through their appropriate binding with MMP-9 or urokinaseplasminogen receptor (uPAR) [34].…”

Section: Vitronectin Receptormentioning

confidence: 99%

Important role of integrins in the cancer biology

Rathinam

Alahari

2010

Cancer Metastasis Rev

201

167

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Adhesion of breast cancer cells is supported by various integrins. Cell adhesion is critical for maintenance of both three-dimensional and normal function of these tissues. Several integrins have been shown to have higher expression levels in metastatic cancers and have been implicated in degrading basement membrane by interacting with proteolytic enzymes. This suggests that a group of integrins plays an important role in migration and invasion through the remodeling of the extracellular matrix. In this review, we highlight recent advances in our understanding of how integrins regulate breast cancer through modulation of the actin cytoskeleton and the mechanisms that regulate this process. Also, we highlight the importance of integrin-binding proteins in cell migration and mechanisms that operate in invasive cells, during breast cancer progression.

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Section: Vitronectin Receptormentioning

confidence: 99%

Important role of integrins in the cancer biology

Rathinam

Alahari

2010

Cancer Metastasis Rev

201

167

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“…Integrin a n b 3 is overexpressed on activated endothelial cells of growing vessels and also on tumor cells such as melanoma, glioma, lung, ovarian and breast cancers, [1][2][3][4][5] and so it represents a promising target structure for the localization of tumor cells, their angiogenesis, and their metastasis by molecular imaging methods. [6] Because cyclic peptides containing the sequence arginine-glycine-aspartic acid (RGD) specifically bind to a n b 3 integrin with high affinities, many examples of radiolabeled cyclic RGD (cRGD) peptides, mainly used for imaging of a n b 3 expression in vivo, can be found.…”

Section: Introductionmentioning

confidence: 99%

Multimerization of cRGD Peptides by Click Chemistry: Synthetic Strategies, Chemical Limitations, and Influence on Biological Properties

et al. 2010

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Integrin α(ν)β(3) is overexpressed on endothelial cells of growing vessels as well as on several tumor types, and so integrin-binding radiolabeled cyclic RGD pentapeptides have attracted increasing interest for in vivo imaging of α(ν)β(3) integrin expression by positron emission tomography (PET). Of the cRGD derivatives available for imaging applications, systems comprising multiple cRGD moieties have recently been shown to exhibit highly favorable properties in relation to monomers. To assess the synthetic limits of the cRGD-multimerization approach and thus the maximum multimer size achievable by using different efficient conjugation reactions, we prepared a variety of multimers that were further investigated in vitro with regard to their avidities to integrin α(ν)β(3.) The synthesized peptide multimers containing increasing numbers of cRGD moieties on PAMAM dendrimer scaffolds were prepared by different click chemistry coupling strategies. A cRGD hexadecimer was the largest construct that could be synthesized under optimized reaction conditions, thus identifying the current synthetic limitations for cRGD multimerization. The obtained multimeric systems were conjugated to a new DOTA-based chelator developed for the derivatization of sterically demanding structures and successfully labeled with (68)Ga for a potential in vivo application. The evaluated multimers showed very high avidities-increasing with the number of cRGD moieties-in in vitro studies on immobilized α(ν)β(3) integrin and U87MG cells, of up to 131- and 124-fold, respectively, relative to the underivatized monomer.

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“…The conjugation efficiency of RGD to NHS-PEG-PLA determined by HPLC was 98.2% (based on RGD peptide). The characterization of RGD-PEG-PLA has been published by our group (21).…”

Section: Preparation and Characterization Of Micellesmentioning

confidence: 99%

“…The synthesis of RGD-PEG-PLA conjugate followed the method in reference (21). Briefly, 500 mg of NHS-PEG-PLA was reacted with 17.5 mg of RGD in 20 mL HEPES (0.1 M, pH=7.5) for 4 h (molar ratio of NHS-PEG-PLA: RGD=1:0.5).…”

Section: Synthesis Of Rgd-peg-pla Copolymermentioning

confidence: 99%