Targeted tumour therapy has proved to be an efficient alternative to overcome the
limitations of conventional chemotherapy. Among several receptors upregulated in cancer
cells, the gastrin-releasing peptide receptor (GRP-R) has recently emerged as a promising
target for cancer imaging, diagnosing and treatment due to its overexpression on cancerous
tissues such as breast, prostate, pancreatic and small-cell lung cancer. Herein, we
report on the in vitro and in vivo selective delivery of the cytotoxic drug daunorubicin
to prostate and breast cancer, by targeting GRP-R. Exploiting many bombesin analogues
as homing peptides, including a newly developed peptide, we produced eleven daunorubicin-containing
peptide–drug conjugates (PDCs), acting as drug delivery systems to safely reach the
tumour environment. Two of our bioconjugates revealed remarkable anti-proliferative
activity, an efficient uptake by all three tested human breast and prostate cancer
cell lines, high stability in plasma and a prompt release of the drug-containing metabolite
by lysosomal enzymes. Moreover, they revealed a safe profile and a consistent reduction
of the tumour volume in vivo. In conclusion, we highlight the importance of GRP-R
binding PDCs in targeted cancer therapy, with the possibility of further tailoring
and optimisation.
