Cyclo (-RGDfK) is a highly efficient and highly specific αvβ3 integrin inhibitor, with an IC₅₀ of only 0.94nM. Cyclo(-RGDfK) can precisely target the αvβ3 integrin on the surface of tumor cells[1]. Thereby Cyclo(-RGDfK) is therefore widely used in studies targeting tumor neovasculature and cancer cells [2]. Cyclo(-RGDfK) can inhibit cancer cell proliferation and migration[3]. Moreover, Cyclo(-RGDfK) is frequently employed as a core ligand for constructing αvβ3-targeted imaging probes or drug delivery systems in tumor imaging studies[4].
In vitro, pretreatment of HepG2 and A549 cells with Cyclo(-RGDfK) (1–10μM) for 4–6h significantly enhanced cellular uptake of the cRGD-PEG-g-(PBYP-ss-CPT) nanoprodrug; compared to the non-cRGD control group, intracellular drug accumulation increased and cell viability was significantly reduced[5]. Pretreatment of A7R5 cells with Cyclo(-RGDfK) (20nM) for 1h followed by 12h stimulation with FPA (10⁻²μM) significantly inhibited cell migration and proliferation, downregulated integrin αVβ3/PI3K/AKT pathway-related protein expression, and reduced Cyclin D1 and PCNA levels[6].
In vivo, intranasal administration of Cyclo(-RGDfK) (2.0μg) 1h prior to modeling significantly inhibited integrin αVβ3/MAPKs/MMP-9 pathway activation, alleviated blood–brain barrier disruption, and improved neurological deficits in a rat model of subarachnoid hemorrhage (SAH)[7]. Cyclo(-RGDfK)-conjugated gold nanoshells (400mg/kg) were injected intravenously into HCT116 colon cancer-bearing nude mice; 24h later, near-infrared laser thermotherapy (47°C × 10min) significantly enhanced tumor vascular-targeted thermal ablation, resulting in more extensive necrosis and vascular disruption[8].
References:
[1] Simeček J, Notni J, Kapp TG, et al. Benefits of NOPO as chelator in gallium-68 peptides, exemplified by preclinical characterization of (68)Ga-NOPO-c(RGDfK). Mol Pharm. 2014 May 5;11(5):1687-95.
[2] Jin ZH, Furukawa T, Degardin M, et al. αVβ3 Integrin-Targeted Radionuclide Therapy with 64Cu-cyclam-RAFT-c(-RGDfK-)4. Mol Cancer Ther. 2016 Sep;15(9):2076-85.
[3] Kalaydina RV, Zhou H, Markvicheva E, et al. Impact of Fucosylation on Self-Assembly of Prostate and Breast Tumor Spheroids by Using Cyclo-RGDfK(TPP) Peptide and Image Object Detection. Onco Targets Ther. 2019 Dec 17;12:11153-11173.
[4] Yoshimoto M, Hayakawa T, Mutoh M, et al. In vivo SPECT imaging with 111In-DOTA-c(RGDfK) to detect early pancreatic cancer in a hamster pancreatic carcinogenesis model. J Nucl Med. 2012 May;53(5):765-71.
[5] Zhou R, Zhang M, He J, et al. Functional cRGD-Conjugated Polymer Prodrug for Targeted Drug Delivery to Liver Cancer Cells. ACS Omega. 2022 Jun 7;7(24):21325-21336.
[6] Fang R, Yang Q, Wu D, et al. Fibrinopeptide a promotes the proliferation and migration of vascular smooth muscle cells by regulating the integrin αVβ3/PI3K/AKT signaling pathway. Mol Biol Rep. 2025 Feb 5;52(1):205.
[7] Okada T, Suzuki H, Travis ZD, et al. SPARC Aggravates Blood-Brain Barrier Disruption via Integrin αVβ3/MAPKs/MMP-9 Signaling Pathway after Subarachnoid Hemorrhage. Oxid Med Cell Longev. 2021 Nov 11;2021:9739977.
[8] Xie H, Diagaradjane P, Deorukhkar AA, et al. Integrin αvβ3-targeted gold nanoshells augment tumor vasculature-specific imaging and therapy. Int J Nanomedicine. 2011;6:259-69.
Cyclo (-RGDfK) 是一种高效且特异性较高的 αvβ3 整合素抑制剂，其半抑制浓度（IC₅₀）仅为 0.94nM，能够精准靶向肿瘤细胞表面的 αvβ3 整合素[1]。因此常被用于肿瘤微血管及癌细胞的靶向治疗的研究中[2]。Cyclo(-RGDfK)可抑制癌细胞的增殖和迁移能力[3]。此外，Cyclo(-RGDfK)还常被用作构建αvβ3靶向示踪剂或药物递送系统的核心配体，用于肿瘤显像研究[4]。
在体外，Cyclo(-RGDfK)（1–10μM）预处理HepG2及A549细胞4–6h，可显著增强细胞对cRGD-PEG-g-(PBYP-ss-CPT)纳米前药的摄取；与无cRGD对照组相比，胞内药物蓄积量增加，并显著降低细胞存活率[5]。Cyclo(-RGDfK)（20nM）预处理A7R5 1h，随后以FPA（10⁻²μM）刺激12h，显著抑制细胞迁移和增殖，并下调integrin αVβ3/PI3K/AKT通路相关蛋白表达，降低Cyclin D1与PCNA水平[6]。
在体内，Cyclo(-RGDfK)（2.0μg）经鼻给药预处理1h，用于治疗蛛网膜下腔出血模型（SAH）大鼠，Cyclo(-RGDfK)显著抑制integrin αVβ3/MAPKs/MMP-9通路激活，减轻血脑屏障破坏及神经功能缺损[7]。400mg/kg的Cyclo(-RGDfK)偶联金纳米壳，经尾静脉注射于HCT116结肠癌裸鼠，24小时后行近红外激光热疗（47℃×10min），可显著增强肿瘤血管靶向热消融效果，诱导更广泛坏死及血管破坏[8]。