Extremely small-sized globular poly(ethylene glycol)-cyclic RGD conjugates targeting integrin αvβ3 in tumor cells

[Display omitted] In this study, we report an extremely small-sized globular poly(ethylene glycol) (gPEG) conjugated with cyclic arginine-glycine-aspartic acid (cRGD) peptide and chlorin e6 (Ce6). This nanoparticle design takes advantage of the biocompatible functional gPEG (3–4nm in diameter) as an extremely small-sized drug carrier, the tumor targeting ability of cRGD, and the photodynamic tumor ablation ability of Ce6. We found that gPEG conjugated with cRGD and Ce6 (cRGD-gPEG-Ce6) exhibited much higher phototoxicity in SKOV-3 tumor cells (which have a very high density of integrin αvβ3 receptors) than in KB cells (which have a very low density of integrin αvβ3 receptors). Accordingly, cRGD-gPEG-Ce6 treatment resulted in a significant regression of in vivo SKOV-3 tumors, highlighting the potential of an extremely small-sized drug carrier platform for site-specific receptor-mediated tumor therapy.