Targeting gastrin-releasing peptide receptors of prostate cancer cells for photodynamic therapy with a phthalocyanine–bombesin conjugate

Sulfonated aluminum phthalocyanines (AlPcS) are potent photosensitizers for the photodynamic therapy (PDT) of cancer. In this study we evaluate the possibility to improve the efficacy of AlPcS-PDT for prostate cancer by targeting tetrasulfonated aluminum phthalocyanines (AlPcS4) to the gastrin-releasing peptide receptor (GRPR) through coupling to bombesin. A mono-carbohexyl derivative of AlPcS4 is attached to 8-Aoc-bombesin(7–14)NH2 via an amide bridge to yield a bombesin–AlPcS4 conjugate linked by a C-14 spacer chain. The conjugate is characterized by mass spectroscopy and shown to bind to the GRPR with a relative binding affinity (RBA) of 2.3, taking bombesin (RBA = 100) as unity. The in vitro photodynamic efficacy of the conjugate against PC-3 human prostate cancer cells is improved by a factor 2.5 over the non-conjugated mono-carbohexyl derivative of AlPcS4.