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Neurotensin branched peptide as a tumor-targeting agent for human bladder cancer
Jlenia Brunetti1, Chiara Falciani1, Barbara Lelli1
1Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
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.
Insights
New neurotensin peptide NT4 shows promise for bladder cancer. Conjugated NT4 can image tumors and deliver chemotherapy, offering potential for personalized bladder cancer diagnosis and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Bladder cancer remains a significant global health challenge, ranking ninth in incidence worldwide.
- Despite advances in multimodal therapy, improved early diagnosis and targeted treatments are crucial.
- Novel molecular agents are needed to enhance diagnostic accuracy and therapeutic efficacy for bladder tumors.
Purpose of the Study:
- To evaluate the potential of tetrabranched neurotensin peptide NT4 as a targeted agent for bladder cancer.
- To assess NT4's utility in cancer-cell imaging and targeted drug delivery for personalized therapy.
- To investigate NT4's efficacy on bladder cancer cell lines and surgical specimens.
Main Methods:
- Conjugation of NT4 peptide with functional units for imaging (fluorophore) and therapy (methotrexate, gemcitabine).
- Testing of fluorophore-conjugated NT4 on bladder cancer cell lines and surgical specimens for tissue differentiation.
- Evaluation of cytotoxic effects of NT4-drug conjugates on human bladder cancer cell lines.
Main Results:
- Fluorophore-conjugated NT4 demonstrated statistically significant distinction between healthy and cancerous bladder tissues (P < 0.05).
- NT4 conjugated with methotrexate or gemcitabine exhibited cytotoxicity against human bladder cancer cell lines at micromolar concentrations.
- The study confirmed NT4's selectivity for bladder cancer tissue.
Conclusions:
- NT4 peptides show potential as tumor-targeting agents for bladder cancer.
- NT4's ability to carry tracers and drugs supports its use in personalized cancer therapy.
- This peptide offers a promising avenue for improved bladder cancer cell tracing and targeted treatment strategies.
