Docetaxel-loaded PAMAM-based poly (γ-benzyl-l-glutamate)-b-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles in human breast cancer and human cervical cancer therapy

Abstract

Taxane-based chemotherapy-loaded drug delivery systems have great potential for cancer treatment. The docetaxel (DTX)-loaded PAMAM-based poly (γ-benzyl-l-glutamate)-b-d-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS) nanoparticles and the docetaxel (DTX)-loaded PAMAM-based poly (γ-benzyl-l-glutamate) (PAM-PBLG) nanoparticles were designed using a modified nanoprecipitation method. The particle size, encapsulation efficiency (EE), and in vitro release characteristics of the nanoparticles were tested. The effects of the two nanoparticles on the cellular uptake and cell viability on human cervical cancer cell line Hela and the human breast cancer cell line MCF-7 were compared. Furthermore, their antitumor efficiency was evaluated through in vivo tumour growth experiment in comparison with free DTX. PAM-PBLG-b-TPGS nanoparticles displayed high EE, smaller diameter, and a nice releasing profile. Besides, based on the high EE and ‘self-controlled’ drug release of the DTX-loaded PAM-PBLG-b-TPGS nanoparticles, they exhibited stronger cytotoxicity (lower survival rate) and higher uptake rate than DTX-loaded PAM-PBLG nanoparticles in Hela cells and MCF-7 cells. Furthermore, compared with DTX-loaded PAM-PBLG nanoparticles and free DTX, DTX-loaded PAM-PBLG-b-TPGS nanoparticles produced a potent anti-tumour effect. Thus, the DTX-loaded PAM-PBLG-b-TPGS nanoparticles provide a novel attractive nanocarrier for the DTX delivery of chemotherapy to human breast cancer cells and human cervical cancer cells.

Keywords:

• Docetaxel
• nanoparticles
• drug delivery
• cancer chemotherapy

Acknowledgement

We thank Dr. Mei Lin at School of Life Sciences, Tsinghua University for the kind gift of the PAM-PBLG Nps and the PAM-PBLG-b-TPGS Nps. Y.Y.Z. and X.S.S. were also supported by Natural Science Foundation of Shenzhen University for Overseas High-Caliber Personnel.

Author contributions

Y.Y.Z conceived the study and designed the experiments. Y.T.W and A.L.Z wrote the manuscript. Y.T.W. and A.L.Z. performed the experiments with the help of Y.Y.Z. and Y.Y.Z. interpreted data and contributed to the discussion. All authors reviewed and concurred with the final manuscript. Y.Y.Z. is the guarantor of this work and as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Disclosure statement

No potential conflicts of interest were disclosed.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (31500940), Science Foundation of Guangdong Province (2016A030310037).