Dual-modified PCL-PEG nanoparticles for improved targeting and therapeutic efficacy of docetaxel against colorectal cancer

Abstract

Polycaprolactone-poly (ethylene glycol) block copolymer (PCL-PEG) based nanoparticles were prepared for the intravenous administration of docetaxel (DTX). PCL-PEG-Tyr and PCL-PEG-Ang were synthesized by using tyrosine (Tyr) and angiopep-2 (Ang) as coupling ligands, and dual-modified PCL-PEG-based nanoparticles (PCL-PEG-Tyr/Ang) were prepared. The physicochemical properties, in vitro drug release, in vitro cytotoxicity, in vitro cellular uptake efficiency, in vivo biodistribution and in vivo antitumor efficacy of PCL-PEG-based nanoparticles were investigated. The PCL-PEG-based nanoparticles were spherical with a mean diameter of 100 nm and high encapsulation efficiencies (> 85%). The results of in vitro drug release showed that the PCL-PEG-based nanoparticles loaded with DTX had sustained-release characteristics. For in vitro cytotoxicity tests, the dual-modified PCL-PEG-based nanoparticles (PCL-PEG-Tyr/Ang) demonstrated the minimum IC₅₀ value (2.94 µg/mL) compared with other PCL-PEG-based nanoparticles. In addition, the cellular uptake of coumarin-6 (C6) in HT29 cells was observed and determined in the PCL-PEG-Tyr/Ang nanoparticles group, which was significantly higher than that in the other PCL-PEG-based groups and C6 solution group. The results of in vivo imaging showed that dual-modified PCL-PEG nanoparticles had better tumor targeting than the other PCL-PEG-based nanoparticles. In the HT29 tumor-xenografted nude mice model, DTX-loaded PCL-PEG-Tyr/Ang nanoparticles also had a significantly higher inhibitory efficacy on tumor growth than Taxotere®-treated group. These results indicated that the dual-modified PCL-PEG-based nanoparticles (PCL-PEG-Tyr/Ang) could be a promising anticancer drug delivery system.

Keywords:

• Tyrosine
• angiopep-2
• targeted drug delivery
• docetaxel
• nanoparticle
• colorectal cancer

Disclosure of interest

The authors declare that there are no conflicts of interest.

Acknowledgements

The authors thanks to Dr. Lin Li, the assistant researcher of Pathology Department of Southwest Hospital, Army Medical University, for the guidance in cytology experiments.

Additional information

Funding

This work was financially supported by Science and Health Joint Medical Research Project of Chongqing Health and Family Planning Commission under Grant [NO. 2018MSXM002], National Science and Technology Major Project under Grant [NO. 2018ZX09J18109-005] and Youth Project of National Natural Science Foundation of China under Grant [NO. 81803029].