Cyclo(RGDyK)

Cyclo(RGDyK) is a potent and selective αVβ3 integrin inhibitor with IC50 of 20 nM^[1].

PEG-b-PLGA micelles without or with Cyclo(RGDyK) conjugation loaded with paclitaxel (PTX) or DiI were prepared and characterized. Drug-loaded micelles were stable in solution, with small diameters (^[5].

A novel drug delivery system Cyclo(RGDyK) -modified Fe3O4 nanoparticles with high DOX load (R-DMP), which combines magnetic targeting, integrin alpha(v)beta3 targeting and high drug loading properties, was developed by chemical coupling both doxorubicin and peptide Cyclo(RGDyK)) on the synthetic dual function magnetic nanoparticles (DMP) using a multi-hand cross-linker poly-L-glutamic acid. D-DMP shows enhanced uptake by integrin alpha(v)beta3 targeting expressing tumor cells and displays stronger cancer cell cytotoxicity^[2].

Cyclo(RGDyK) administration weakened the exercise-related improvement of vBMD, BV/TV, and ALP intensity in bone^[4]. By blocking irisin receptor (αV/β5), Cyclo(RGDyK) could reduce irisin-induced signalings. When irisin pathways were blocked, some osteoblastogenic genes were decreased, which might contribute to the Cyclo(RGDyK) -induced reduction of osteogenic differentiation^[3].

References:
[1]: Haubner R, Wester HJ, et,al. Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med. 2001 Feb;42(2):326-36. PMID: 11216533.
[2]: Guo L, Ding W, et,al. The C(RgdyK)-conjugated Fe3O4 nanoparticles with high drug load for dual-targeting integrin alpha(v)beta3-expressing cancer cells. J Nanosci Nanotechnol. 2014 Jul;14(7):4858-64. doi: 10.1166/jnn.2014.8691. PMID: 24757954.
[3]: Kim H, Wrann CD, et,al. Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors. Cell. 2018 Dec 13;175(7):1756-1768.e17. doi: 10.1016/j.cell.2018.10.025. Erratum in: Cell. 2019 Jul 11;178(2):507-508. PMID: 30550785; PMCID: PMC6298040.
[4]:Zhao R, Zhou Y, et,al. Irisin Regulating Skeletal Response to Endurance Exercise in Ovariectomized Mice by Promoting Akt/β-Catenin Pathway. Front Physiol. 2021 Mar 25;12:639066. doi: 10.3389/fphys.2021.639066. PMID: 33841178; PMCID: PMC8027323.
[5]:Yin J, Li Z, et,al. Cyclic RGDyK conjugation facilitates intracellular drug delivery of polymeric micelles to integrin-overexpressing tumor cells and neovasculature. J Drug Target. 2011 Jan;19(1):25-36. doi: 10.3109/10611861003663531. Epub 2010 Mar 16. PMID: 20233083.