A Four-Arm Star-Shaped Poly(ethylene glycol) (StarPEG) Platform for Bombesin Peptide Delivery to Gastrin-Releasing...

We present the design, synthesis, and characterization of a novel cancer biomarker delivery platform, the star-shaped four-arm poly(ethylene glycol) (StarPEG). Using the multidisplay platform we were able to synthesize a bombesin (BBN) positron emission tomography (PET) probe featuring four copies of 8-Aoc-BBN peptides (where 8-Aoc is 8-aminooctanic acid), which we named StarPEG-BBN. Cell binding studies showed that StarPEG-BBN had a good binding affinity to PC3 cells (IC₅₀ = 65.3 ± 3.4 nM). Cell uptake studies showed that the binding was specific (blocking vs no-blocking, P < 0.05). Mice were then implanted with PC3 cells and divided into two groups, one injected with ⁶⁴Cu-StarPEG-BBN and the other 250 μg of unlabeled 8-Aoc-BBN along with ⁶⁴Cu-StarPEG-BBN. In vivo images revealed that StarPEG-BBN had good tumor uptake (4.2 ± 0.4% ID/g at 4 h post-injection (p.i.)) and was significantly blocked by coinjection of unlabeled 8-Aoc-BBN at 4 h p.i. (P = 0.003). The small animal PET quantification was further verified by the biodistribution study at 24 h p.i. Our study demonstrated that the novel four-arm PEG platform StarPEG as a cancer biomarker multimerization/delivery platform conserves binding specificity, improves drug loading, is capable of achieving good tumor uptake, and has great potential in cancer treatment and molecular imaging.