2. Academic Validation
  3. New somatostatin-drug conjugates for effective targeting pancreatic cancer

New somatostatin-drug conjugates for effective targeting pancreatic cancer

  • Bioorg Med Chem. 2018 Jul 30;26(13):3825-3836. doi: 10.1016/j.bmc.2018.06.032.
E Ragozin 1,  A Hesin 2,  A Bazylevich 1,  H Tuchinsky 3,  A Bovina 1,  T Shekhter Zahavi 4,  M Oron-Herman 5,  G Kostenich 5,  M A Firer 6,  T Rubinek 2,  I Wolf 2,  G Luboshits 6,  M Y Sherman 3,  G Gellerman 7
Affiliations

Affiliations

  • 1 Department of Chemical Sciences, Ariel University, Ariel 40700, Israel.
  • 2 The Oncology Institute, Tel Aviv Souraski Medical Center, Tel-Aviv 62431, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
  • 3 Department of Molecular Biology, Ariel University, Ariel 40700, Israel.
  • 4 The Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel.
  • 5 The Advanced Technologies Center, Sheba Medical Center, Tel Hashomer, 52621, Israel.
  • 6 Department of Chemical Engineering, Ariel University, Ariel 40700, Israel.
  • 7 Department of Chemical Sciences, Ariel University, Ariel 40700, Israel. Electronic address: garyg@ariel.ac.il.
PMID: 30017114 DOI: 10.1016/j.bmc.2018.06.032
Abstract

Pancreatic Cancer poorly responds to available drugs, and finding novel approaches to target this Cancer type is of high significance. Here, based on a common property of pancreatic Cancer cells to express somatostatin receptors (SSTR), we designed drug conjugates with novel somatostatin-derived cyclic Peptides (SSTp) with broad selectivity towards SSTR types to facilitate drug targeting of the pancreatic Cancer cells specifically. Uptake of our newly designed SSTps was facilitated by SSTRs expressed in the pancreatic cancers, including SSTR2, SSTR3, SSTR4 and SSTR5. Three major drugs were conjugated to our best SSTps that served as delivery vehicles, including Camptothecin (CPT), Combretastatin-4A (COMB) and Azatoxin (AZA). All designed drug conjugates demonstrated penetration to pancreatic Cancer cell lines, and significant toxicity towards them. Furthermore, the drug conjugates specifically accumulated in tumors in the animal xenograft model, though some accumulation was also seen in kidney. Overall these findings lay the basis for development of novel drug series that could target the fatal pancreatic Cancer.

Keywords

Pancreatic cancer; Peptide conjugate; SPPS; SSTR; Stability profiles; Targeted drug delivery.

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