A New NT4 Peptide-Based Drug Delivery System for Cancer Treatment.

Marco Fragai,Silvia Scali,Alessandro Pini,Sara Piantini,Lorenzo Depau,Stefano Menichetti,Jlenia Brunetti,Luisa Bracci,Chiara Falciani,Giulia Cipriani

doi:10.3390/molecules25051088

Abstract

The development of selective tumor targeting agents to deliver multiple units of chemotherapy drugs to cancer tissue would improve treatment efficacy and greatly advance progress in cancer therapy. Here we report a new drug delivery system based on a tetrabranched peptide known as NT4, which is a promising cancer theranostic by virtue of its high cancer selectivity. We developed NT4 directly conjugated with one, two, or three units of paclitaxel and an NT4-based nanosystem, using NIR-emitting quantum dots, loaded with the NT4 tumor-targeting agent and conjugated with paclitaxel, to obtain a NT4-QD-PTX nanodevice designed to simultaneously detect and kill tumor cells. The selective binding and in vitro cytotoxicity of NT4-QD-PTX were higher than for unlabeled QD-PTX when tested on the human colon adenocarcinoma cell line HT-29. NT4-QD-PTX tumor-targeted nanoparticles can be considered promising for early tumor detection and for the development of effective treatments combining simultaneous therapy and diagnosis.

Highlights

Drug delivery systems can enhance therapeutic effects and have fewer side- and adverse effects, as well as reduced chemotherapic toxicity
Peptide-based systems may be used in drug delivery, owing to specific chemical properties of peptides, which are easy to obtain by chemical synthesis and can be modified to deliver therapeutic agents including drugs and diagnostic molecules
We previously reported a stable tetrabranched peptide, named NT4, which binds with high selectivity to human cancer cells and tissues and efficiently and selectively delivers drugs or tracers for cancer cell imaging or therapy

Summary

Introduction

Drug delivery systems can enhance therapeutic effects and have fewer side- and adverse effects, as well as reduced chemotherapic toxicity. Peptide-based systems may be used in drug delivery, owing to specific chemical properties of peptides, which are easy to obtain by chemical synthesis and can be modified to deliver therapeutic agents including drugs and diagnostic molecules. These can be coupled to the carrier peptide by tailored chemical bonds [1,2,3]. In the last few years, several strategies have been considered to improve the metabolic stability through chemical approaches aimed to modify the original peptide sequences.

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