Advancement in integrin facilitated drug delivery

Arosio, Daniela; Casagrande, C

doi:10.1016/j.addr.2015.12.001

Cited by 130 publications

(89 citation statements)

References 272 publications

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“…12 Moreover, integrins are frequently overexpressed in tumour endothelial cells as well as on various tumour cells. Owing to the ability of some integrin subtypes (especially α V β 3 ) to selectively recognize the tripeptide motif -Arg-Gly-Asp-, RGD-containing peptides, particularly the conjugable version of Cilengitide, c(RGDfK), have been used for tumour imaging and for targeted drug delivery of cytotoxic compounds, 13 including metal-based anticancer agents. 14 In recent years, only few examples of caged versions of RGD peptides have been described by modifying the Asp residue 7ce with a photolabile protecting group or by incorporating an o-nitrobenzyl group within the backbone skeleton.…”

Section: Introductionmentioning

confidence: 99%

A Green Light-Triggerable RGD Peptide for Photocontrolled Targeted Drug Delivery: Synthesis and Photolysis Studies

et al. 2016

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TOC ABSTRACT GRAPHIC 2 ABSTRACTWe describe for the first time the synthesis and photochemical properties of a coumarin-caged cyclic RGD peptide, and demonstrate that uncaging can be efficiently performed with biologically-compatible green light. This was accomplished by using a new dicyanocoumarin derivative (DEAdcCE) for the protection of the carboxyl function at the side chain of the aspartic acid residue, which was selected on the basis of Fmoc-tBu SPPS compatibility and photolysis efficiency. The shielding effect of a methyl group incorporated in the coumarin derivative near the ester bond linking both moieties in combination with the use of acidic additives such as HOBt or Oxyma during the basic Fmoc-removal treatment was found to be very effective for minimizing aspartimide-related side-reactions. In addition, a conjugate between the dicyanocoumarin-caged cyclic RGD peptide and ruthenocene, which was selected as a metallodrug model cargo, has been synthesized and characterized. The fact that green-light triggered photoactivation can be efficiently performed both with the caged peptide and with its ruthenocenoyl bioconjugate reveals a great potential for DEAdcCE-caged peptide sequences as selective drug carriers in the context of photocontrolled targeted anticancer strategies.3

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Section: Introductionmentioning

confidence: 99%

A Green Light-Triggerable RGD Peptide for Photocontrolled Targeted Drug Delivery: Synthesis and Photolysis Studies

et al. 2016

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“…Because of the side effect profiles of generic cancer chemotherapeutic agents, there is substantial interest in developing molecular mechanisms that direct these drugs specifically to cancer cells. [6][7][8][9][10][11] Tetraiodothyroacetic acid (tetrac) is a ligand of a specific target on the extracellular domain of plasma membrane integrin αvβ3, 12 an integrin generously expressed by cancer cells and by dividing endothelial cells of tumor-relevant blood vessels. We have covalently bonded tetrac via a short diaminopropane linker to a 150-200 nm poly(lactic-co-glycolic acid) (PLGA) nanoparticle (Nanotetrac, nano-diamino-tetrac [NDAT]), as shown in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac

Sudha

Bharali

Yalçın

et al. 2017

IJN

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The tetraiodothyroacetic acid (tetrac) component of nano-diamino-tetrac (NDAT) is chemically bonded via a linker to a poly(lactic- co -glycolic acid) nanoparticle that can encapsulate anticancer drugs. Tetrac targets the plasma membrane of cancer cells at a receptor on the extracellular domain of integrin αvβ3. In this study, we evaluate the efficiency of NDAT delivery of paclitaxel and doxorubicin to, respectively, pancreatic and breast cancer orthotopic nude mouse xenografts. Intra-tumoral drug concentrations were 5-fold (paclitaxel; P <0.001) and 2.3-fold (doxorubicin; P <0.01) higher than with conventional systemic drug administration. Tumor volume reductions reflected enhanced xenograft drug uptake. Cell viability was estimated by bioluminescent signaling in pancreatic tumors and confirmed an increased paclitaxel effect with drug delivery by NDAT. NDAT delivery of chemotherapy increases drug delivery to cancers and increases drug efficacy.

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“…Integrins have the ability to recognize multiple ligands and may bind to interaction partners with an RGD sequence (Arg-Gly-Asp), an acidic motif termed "LDV," or a collagenous GFOGER motif. [47][48][49][50][51][52][53] VN, which was identified as a component of the serum corona for dPGS but not for dPGOH NPs, can interact with αvβ3 integrin and could thus possibly be important for the uptake of dPGS NPs as well. [54][55][56] For FBS-treated TiO 2 NPs, it was already shown that cellular uptake into human lung carcinoma cells (A549) was reduced when cells were pre-treated with anti-VN antibodies.…”

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confidence: 99%

The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles

Bewersdorff

Vonnemann

Kanik

et al. 2017

IJN

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Nanoparticles (NPs) have gained huge interest in the medical field, in particular for drug delivery purposes. However, binding of proteins often leads to fast NP uptake and rapid clearance, thereby hampering medical applications. Thus, it is essential to determine and control the bio–nano interface. This study investigated the serum protein interactions of dendritic polyglycerols (dPGs), which are promising drug delivery candidates by means of two dimensional gel electrophoresis (2DE) in combination with mass spectrometry. In order to investigate the influence of surface charge, sulfated (sulfated dendritic polyglycerol [dPGS]) and non-sulfated (dPGOH) surfaces were applied, which were synthesized on a gold core allowing for easier separation from unbound biomolecules through centrifugation. Furthermore, two different sizes for dPGS were included. Although size had only a minor influence, considerable differences were detected in protein affinity for dPGS versus dPGOH surfaces, with dPGOH binding much less proteins. Cellular uptake into human CD14 + monocytes was analyzed by flow cytometry, and dPGOH was taken up to a much lower extent compared to dPGS. By using a pull-down approach, possible cellular interaction partners of serum pre-incubated dPGS-Au20 NPs from the membrane fraction of THP-1 cells could be identified such as for instance the transferrin receptor or an integrin. Clathrin-mediated endocytosis was further investigated using chlorpromazine as an inhibitor, which resulted in a 50% decrease of the cellular uptake of dPGS. This study could confirm the influence of surface charge on protein interactions and cellular uptake of dPGS. Furthermore, the approach allowed for the identification of possible uptake receptors and insights into the uptake mechanism.

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Advancement in integrin facilitated drug delivery

Cited by 130 publications

References 272 publications

A Green Light-Triggerable RGD Peptide for Photocontrolled Targeted Drug Delivery: Synthesis and Photolysis Studies

A Green Light-Triggerable RGD Peptide for Photocontrolled Targeted Drug Delivery: Synthesis and Photolysis Studies

Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac

The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles

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