αvβ3 integrin-targeted pH-responsive dendritic nanocarriers for enhanced anti-tumor efficacy of docetaxel against breast cancer

Abstract

The hyperbranched biodegradable dendrimer (Boltron® H40) has received mounting attention as a result of its efficient encapsulation of therapeutic molecules and sustained release of the payloads into target cancer cells. Herein, we report the Boltron® H40 dendrimer conjugated with polyethylene glycol (PEG) and cRGDfc peptide ligand (i.e., H40-PEG-cRGDfc) for higher loading and targeted delivery of Docetaxel (DTX) to breast cancer cells. The characterization of synthesized nanoparticles was carried out by dynamic light scattering (DLS), 1H NMR, Fourier transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). The H40-PEG-cRGDfc exhibited higher DTX encapsulation with 49.83 % drug loading. Interestingly, the DTX release profile of H40-PEG-cRGDfc showed a higher release of DTX at the acidic pH of 5.0 compared to physiological pH. The targeted H40-PEG-cRGDfc nanoparticles showed higher internalization ability towards breast cancer cell lines MDA-MB-231 and 4T1. The toxicity study of targeted and non-targeted NPs on NIH-3T3 normal mice cell line showed no apparent toxicity to the cells. The treatment of DTX-loaded targeted NPs (DTX-H40-PEG-cRGDfc) on MDA-MB-231 (IC50 10.06 nM) and 4T1 (IC50 8.67 nM) cell lines confirmed significant anti-breast cancer activity of designed formulation. This study demonstrated that cRGDfc targeted, DTX loaded, Boltron® H40 dendrimer had a significant breast cancer cell-killing ability. The experimental findings of this study displayed future opportunities for developing a targeted nano-therapeutic platform in breast cancer treatment.