Self-assembled nanoparticles covalently consisting of doxorubicin and EDB fibronectin specific peptide for solid tumour treatment

Abstract

In this study, we developed a facile modality to prepare a drug delivery system consisting of doxorubicin (DOX) and a ZD2 motif (DOX-ZD2) for potential clinical use treating solid tumours. The DOX-ZD2 nanoparticles with a diameter of ∼160 nm were prepared in a selective solvent, water. The DOX-ZD2 nanoparticles possessed great stability in phosphate buffer solution (PBS) and were fairly stable in a low concentration of thiols (20 μM). However, a high concentration of thiols (10 mM) remarkably promoted the deconjugation of DOX-ZD2. In vitro study indicated that DOX-ZD2 showed great preferential cellular uptake in PC3 cells compared with control groups, DOX-conjugated scramble peptide (sequence: CERAK) (DOX-Contr) and free DOX, and high cell suppression as well. The PC3 tumour model was used to investigate the therapeutic efficacy of DOX-ZD2, DOX-Contr, and free DOX. Encouragingly, the DOX-ZD2 nanoparticles showed strong anti-tumour ability in comparison with DOX-Contr and, in particular, free DOX. Our study certainly provides a novel modality for preparing DOX-contained drug delivery systems for solid tumour therapy in clinic.