cRGD (αvβ3 integrin receptor)-functional thermo/pH sensitive chitosan copolymer magnetic nanoparticles for targeted therapy of breast cancer.

In this study, cyclic Arg-Gly-Asp-D-Phe-Lys (cRGD)-conjugated multifunctional thermo/pH-sensitive magnetic nanoparticles (MNPs) based on chitosan (CS) were designed and synthesized for the target delivery of doxorubicin (DOX). First, CS copolymer (CS/CP) was synthesized, and then, CS/CP MNPs were prepared through a complex between the COOH groups of CS/CP and Fe₃O₄MNPs. Ultimately, cRGD was conjugated to the NH₂ groups of the CS/CP MNPs as an integrin αvβ₃ receptor-targeting ligand. The structure, size, morphology, and magnetic response of RGD/CS/CP MNPs were characterized using FT-IR, ¹H NMR, and UV-Vis spectroscopies, SEM-EDX analysis, X-ray diffraction, dynamic light scattering, and a vibrating sample magnetometer. The DOX loading capacity (DLC%) and encapsulation efficiency (EE%) were about 33.26 % and 95 %, respectively, and the DOX release rate was higher at pH = 5.8. The MTT test showed that the DOX-loaded cRGD/CS/CP MNPs had significant toxicity against MCF-7 cells. The cellular uptake analysis confirmed that cRGD/CS/CP MNPs could be easily internalized by MCF-7 cells through αvβ₃ integrin receptor-mediated endocytosis. The assessment of apoptosis/necrosis indicated a higher apoptosis rate of cRGD/CS/CP MNPs-DOX (80.15 %) compared to free DOX (26.99 %). Therefore, the prepared novel nanocarrier could be a good candidate as a targeted delivery agent for breast cancer treatment.