biostudies-literatureGomena JNational Laboratories Excellence programHungarian Thematic Excellence ProgrammeNational Research, Development and Innovation OfficeNational Research, Development and Innovation Office, HungaryEuropean Union's Horizon 2020 research and innovation programmeEuropean Regional Development Fund (EU and State of Hungary)European Union and the State of HungaryEuropean Union’s Horizon 2020 research and innovation programme3400https://www.ebi.ac.uk/biostudies/studies/S-EPMC9967152biostudies-literatureUnknown24(4)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.International journal of molecular sciencesTargeting the Gastrin-Releasing Peptide Receptor (GRP-R) in Cancer Therapy: Development of Bombesin-Based Peptide-Drug Conjugates.PMC9967152VEKOP-2.3.3-15-2017-000202022-2.1.1-NL-2022-00010NKFIH K119552 and 2018-1.2.1-NKP-2018-00005TKP2021-EGA-44NKFIH K1195528613162018-1.2.1-NKP-2018-00005Biri-Kovacs BSoos ABosze SGomena JVari BTovari JMezo GRanđelovic IOlah-Szabo RBorbely AfalseTargeting the Gastrin-Releasing Peptide Receptor (GRP-R) in Cancer Therapy: Development of Bombesin-Based Peptide-Drug Conjugates.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.2023-01-01T00:00:00Z2023 Feb2026-05-16T03:14:29.157Z2025-02-18T23:44:44.367ZS-EPMC99671523683481510.3390/ijms24043400