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].
参考文献:
[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.
Cyclo(RGDyK) 是一种有效的选择性 αVβ3 整合素抑制剂，IC50 为 20 nM[1]。
制备并表征了负载有紫杉醇 (PTX) 或 DiI 的没有或有 Cyclo(RGDyK) 缀合的 PEG-b-PLGA 胶束。载药胶束在溶液中稳定，直径小([5].
一种新型药物递送系统 Cyclo(RGDyK) - 修饰的 Fe3O4 纳米颗粒具有高 DOX 负载 (R-DMP)，它结合了磁性靶向、整合素 alpha(v)beta3 靶向和高药物负载特性，通过化学耦合两者开发阿霉素和肽环 (RGDyK)) 在合成双功能磁性纳米粒子 (DMP) 上使用多手交联剂聚-L-谷氨酸。 D-DMP 可增强靶向表达肿瘤细胞的整合素 alpha(v)beta3 的摄取，并表现出更强的癌细胞细胞毒性[2]。
Cyclo(RGDyK) 给药削弱了骨骼中 vBMD、BV/TV 和 ALP 强度的运动相关改善[4]。通过阻断鸢尾素受体 (αV/β5)，Cyclo(RGDyK) 可以减少鸢尾素诱导的信号传导。当鸢尾素通路被阻断时，一些成骨细胞基因减少，这可能有助于 Cyclo(RGDyK) 诱导的成骨分化减少[3]。
| Cell experiment [1]: | |
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Cell lines |
B16-F10 cells and HUVEC |
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Preparation Method |
Dil-loaded micellar formulations with different Cyclo(RGDyK) densities (0%, 10%, 20%) were incubated with B16-F10 cells or HUVEC in six-well plates for 3 h at 37°C at a final concentration of 0.5 ug/mL or 0.1 ug/mL Dil diluted in culture media, respectively. And the cells incubated with medium were used as negative controls. For the competition experiments, free Cyclo(RGDyK) (0.8 mM for B16-F10 and 1.6 μM for HUVEC) was pre-incubated with cells for 1 h, followed by continued co-incubation with Cyclo(RGDyK)-Dil-PM with 20% cRGDyK for 3 h. Then, cells were washed, trypsinized, and neutralized. After centrifugation at 1200 rpm for 5 min, cells were resuspended in PBS, followed by filtra |
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Reaction Conditions |
0.8 mM for B16-F10 and 1.6 μM for HUVEC Cyclo(RGDyK) for 1 h |
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Applications |
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 (<80 nm) and a low critical micelle concentration. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6 mice |
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Preparation Method |
Forty 3-month old female C57BL/6 mic were randomly allocated into four groups: (1) Sham-operated (Sham); (2) ovariectomized; (3) Ovx plus 8-week downhill running exercise (Ex); (4) Ovx plus exercise and received twice weekly injection of Cyclo(RGDyK) protein (a putative anti-irisin receptor agents) (ExRg). |
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Dosage form |
2.5 mg/kg Cyclo(RGDyK) twice a week(tail vein injection) |
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Applications |
Cyclo(RGDyK) administration weakened the exercise-related improvement of vBMD, BV/TV, and ALP intensity in bone. |
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参考文献: [1]. 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. | |
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