Neurotensin Branched Peptide as a Tumor-Targeting Agent for Human Bladder Cancer

Abstract

Despite recent advances in multimodal therapy, bladder cancer still ranks ninth in worldwide cancer incidence. New molecules which might improve early diagnosis and therapeutic efficiency for tumors of such high epidemiological impact therefore have very high priority. In the present study, the tetrabranched neurotensin peptide NT4 was conjugated with functional units for cancer-cell imaging or therapy and was tested on bladder cancer cell lines and specimens from bladder cancer surgical resections, in order to evaluate its potential for targeted personalized therapy of bladder cancer. Fluorophore-conjugated NT4 distinguished healthy and cancer tissues with good statistical significance (P < 0.05). NT4 conjugated to methotrexate or gemcitabine was cytotoxic for human bladder cancer cell lines at micromolar concentrations. Their selectivity for bladder cancer tissue and capacity to carry tracers or drugs make NT4 peptides candidate tumor targeting agents for tracing cancer cells and for personalized therapy of human bladder cancer.

Antimicrobial Dendrimeric Peptides: Structure, Activity and New Therapeutic Applications

“…NT4 was tested on HT-1376 and T24 bladder cancer cell lines in vitro and on human cancer samples obtained from patients that underwent radical cystectomy or endoscopic transurethral resection of the bladder, comparing results with those obtained with the healthy tissue counterpart of the same patients to evaluate its ability to recognize specific membrane receptors and to be internalized. NT4 conjugated to fluorophores distinguished cancer and healthy tissues with good statistical significance, and NT4 conjugated to methotrexate or gemcitabine was found to be cytotoxic for human bladder cancer cell lines at micromolar concentrations [49]. …”

Native Chemical Ligation Directed by Photocleavable Peptide Nucleic Acid (PNA) Templates

“…Finally, photolysis provided traceless cleavage of the templating strands to provide ligated peptide 19 . The strategy offers the possibility of synthesizing branched peptides with therapeutic potential . The template‐mediated ligation of C‐ to N‐terminally linked and N‐terminally linked peptides has been explored .…”

Branched peptides as bioactive molecules for drug design

“…NT4 efficiently discriminated between tumor and healthy tissue in human surgical samples from colon and pancreas adenocarcinomas and urinary bladder cancer in a large number of patients . Using NT4 conjugated with methotrexate or 5‐fluoro‐2′‐deoxyuridine, the authors obtained 60% and 50% reduction in tumor growth, respectively, in mice.…”

“…NT4 bound specifically with high affinity to membrane‐sulfated glycosaminoglycans (GAG) and to different membrane endocytic receptors belonging to the low‐density lipoprotein receptor family, including LRP1 and LRP6, all already known as potential druggable tumor markers involved in cancer biology . NT4 was much more selective than native monomeric analogues for binding to different human cancer cells and tissues . A versatile coupling method, which allows different tracing probes or chemotherapeutics to be conjugated with NT4, was also set up for selective imaging and killing of cancer cells .…”