2. Academic Validation
  3. N-acetylgalactosamine-decorated nanoliposomes for targeted delivery of paclitaxel to hepatocellular carcinoma

N-acetylgalactosamine-decorated nanoliposomes for targeted delivery of paclitaxel to hepatocellular carcinoma

  • Eur J Med Chem. 2021 Oct 15:222:113605. doi: 10.1016/j.ejmech.2021.113605.
Tingshen Li 1,  Peng Yu 1,  Yihao Chen 1,  Baoying Sun 1,  Peijie Dong 1,  Tao Zhu 2,  Xin Meng 3
Affiliations

Affiliations

  • 1 China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin, 300457, China.
  • 2 China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin, 300457, China; CanSino Biologics Inc., Tianjin Enterprise Key Laboratory of Respiratory Bacterial Recombination and Conjugated Vaccine, Tianjin, 300457, China.
  • 3 China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin, 300457, China. Electronic address: [email protected].
PMID: 34126457 DOI: 10.1016/j.ejmech.2021.113605
Abstract

In this study, we designed and developed a novel asialoglycoprotein receptor (ASGPR)-targeted PEGylated paclitaxel (PTX) nanoliposome for hepatocellular carcinoma (HCC). N-acetylgalactosamine with α configuration (Tn) was synthesized and used as the active targeting ligand. Notably, Tn modified nanoliposomes loaded with PTX (Tn-Lipo-PTX) showed a narrow distribution (PDI = 0.18-0.20) with 74 ± 0.36 nm of average sizes. Tn-Lipo-PTX has a high encapsulation efficiency of more than 93.0% and 13% of drug loading (DL). Compared with no targeted Con-Lipo-PTX, Tn-Lipo-PTX showed lower and sustained release characteristic in PBS in vitro. Tn targeting ASGPR was confirmed by HepG-2 cells uptake experiment by fluorescence microscopy analysis. Tn-Lipo-PTX accumulated in HepG-2 cells and this process was inhibited by adding Tn ligand, supporting receptor-mediated endocytosis mechanism. MTT assays was implemented in four cell lines. Tn-Lipo-PTX exhibited superior inhibition against ASGPR on over-expressing HepG-2 (IC50 = 1.93 nM). The cell cycle experiments showed that Tn-Lipo-PTX could efficiently increase the percentage of cells arrest in the G2/M phase. Through western blotting analysis, the β-tubulin and cyclin B1 expression in the Tn-Lipo-PTX group were significantly higher compared with Other groups and the CDK1 was down-regulated compared with PTX group, which indicated that targeting Liposome delivery system could not only change periodic proteins expression, but also improve the killing effect of PTX on hepatocarcinoma cell. Tn-installed PEGylated nanoliposomes have a great potential for targeted Cancer chemotherapy.

Keywords

Asialoglycoprotein receptor; Hepatocyte-selective targeting; Liposomes; Paclitaxel.

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