Application of RGD Peptides in Smart Targeted Nanodrug-Delivery Systems for Cancer Therapy

Cancer remains one of the major challenges facing healthcare systems worldwide. Although conventional treatments such as chemotherapy and radiotherapy are effective, their nonspecific distribution, systemic toxicity, poor solubility, and short circulation half-life often limit therapeutic outcomes. Smart nanodrug-delivery systems have emerged as promising platforms for improving drug solubility, prolonging circulation time, enabling controlled drug release, and enhancing tumor accumulation. Among active-targeting ligands, the tripeptide arginine-glycine-aspartic acid (RGD) has attracted considerable attention because of its high affinity for integrin receptors, particularly avẞ۳ and avẞ۵, which are frequently overexpressed on tumor cells and tumor-associated endothelial cells. RGD-modified nanocarriers can promote receptor-mediated cellular uptake and improve the selective accumulation of therapeutic agents in tumors. Linear and cyclic RGD peptides, as well as advanced derivatives such as iRGD, have been incorporated into various nanocarriers, including liposomes, polymeric nanoparticles, polymeric micelles, mesoporous silica nanoparticles, gold nanoparticles, magnetic nanoparticles, and dendrimers. The structural conformation, linker properties, ligand density, attachment site, and spatial orientation of RGD strongly influence targeting efficiency. This review discusses the structural characteristics and major types of RGD peptides, their interactions with integrins, their applications in smart targeted nanodrug-delivery systems, and the associated therapeutic advantages and limitations. Current challenges and future perspectives for the clinical translation of RGD-based nanomedicine are also addressed.

کلیدواژه ها:

RGD peptide ، integrins ، cancer therapy ، iRGD ، nanocarriers