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Updated: Jul 12, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Synthesis and biological activity of stable branched neurotensin peptides for tumor targeting
Chiara Falciani1, Monica Fabbrini, Alessandro Pini
1Department of Molecular Biology, University of Siena, Siena, Italy 53100. chiarafalciani@unisi.it
Abstract:
Receptors for endogenous regulatory peptides, like the neuropeptide neurotensin, are overexpressed in several human cancers and can be targets for peptide-mediated tumor-selective therapy. Peptides, however, have the main drawback of an extremely short half-life in vivo. We showed that neurotensin and other endogenous peptides, when synthesized as dendrimers, retain biological activity and become resistant to proteolysis. Here, we synthesized the neurotensin functional fragment NT(8-13) in a tetrabranched form linked to different units for tumor therapy or diagnosis. Fluorescent molecules were used to monitor receptor binding and internalization in HT29 human adenocarcinoma cells and receptor binding in HT29 tumor xenografts in nude mice. Linking of chemotherapic molecules like chlorin e6 and methotrexate to dendrimers resulted in a dramatic increase in drug selectivity, uptake of which by target cells became dependent on peptide receptor binding. When nude mice carrying human tumor xenografts were treated with branched NT(8-13)-methotrexate, a 60% reduction in tumor growth was observed with respect to mice treated with the free drug.
Insights
Dendrimer-based neurotensin peptides show promise for cancer therapy. These modified peptides resist breakdown and deliver chemotherapy drugs selectively to tumors, significantly reducing tumor growth in preclinical models.
Area of Science:
- Biochemistry
- Oncology
- Nanotechnology
Background:
- Neurotensin receptors are overexpressed in human cancers, presenting a therapeutic target.
- Peptides have short in vivo half-lives, limiting their therapeutic potential.
- Dendrimer synthesis can enhance peptide stability and biological activity.
Purpose of the Study:
- To synthesize and evaluate dendrimer-based neurotensin fragments for cancer therapy and diagnosis.
- To assess the tumor-targeting and therapeutic efficacy of these novel constructs.
Main Methods:
- Synthesis of tetrabranched neurotensin fragment NT(8-13) linked to diagnostic or therapeutic moieties.
- In vitro studies using HT29 human adenocarcinoma cells to monitor receptor binding and internalization.
- In vivo studies using HT29 tumor xenografts in nude mice to evaluate tumor targeting and therapeutic response.
Main Results:
- Dendrimer-conjugated neurotensin fragments retained biological activity and resistance to proteolysis.
- Chemotherapy drugs (chlorin e6, methotrexate) linked to dendrimers showed increased selectivity for cancer cells.
- Treatment with branched NT(8-13)-methotrexate reduced tumor growth by 60% compared to free methotrexate in vivo.
Conclusions:
- Dendrimer conjugation is a viable strategy to improve the therapeutic index of peptide-based cancer therapies.
- Targeted delivery of chemotherapy via dendrimer-peptide conjugates offers enhanced selectivity and efficacy.
- Branched NT(8-13)-methotrexate demonstrates significant preclinical efficacy against human tumor xenografts.
