RGD-conjugated solid lipid nanoparticles inhibit adhesion and invasion of αvβ3 integrin-overexpressing breast cancer cells

Drug Delivery and Translational Research
Dan ShanXiao Yu Wu

Abstract

αvβ3 integrin receptors expressed on cancer cell surfaces play a crucial role in promoting tumor angiogenesis and cancer cell metastasis. Thus, cyclic arginyl-glycyl-aspartic acid (cRGD) peptides have been explored as a αvβ3 integrin receptor-specific targeting moiety for the targeted delivery of nanoparticle-loaded therapeutics. However, our previous study showed that cyclic RGD could act as a double-edged sword that, on one hand, extended the retention of cRGD-modified solid lipid nanoparticles (RGD-SLNs) at αvβ3 integrin receptor overexpressing breast carcinoma, and yet on the other hand, decreased the amount of tumor accumulation of RGD-SLNs attributable to the greater uptake by the mononuclear phagocyte system (MPS). Therefore, we aimed to optimize the RGD-decorated nanoparticle systems for (1) inhibiting αvβ3 integrin receptor overexpressing tumor cell metastasis and (2) increasing nanoparticle accumulation to tumor site. SLNs with cRGD content ranging from 0 to 10 % mol of total polyethyleneglycol (PEG) chains were synthesized. The binding of RGD-SLNs with αvβ3 integrin receptors increased with increasing cRGD concentration on the nanoparticles. RGD-SLNs were demonstrated to inhibit MDA-MB-231 cell adhesion to fibronecti...Continue Reading

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