A study on the antitumor effect of gemcitabine polybutylcy- anoacrylate nanoparticles coupled with Mucin 1 monoclonal antibody on pancreatic cancer in vitro and in vivo

J Cancer Res Ther. 2021 Dec;17(7):1702-1708. doi: 10.4103/jcrt.jcrt_627_21.

Abstract

Context: Previous studies have discovered a high expression rate of Mucin 1 (MUC1) in pancreatic cancer tissue, and its abnormal glycosylation causes MUC1 to expose new protein epitopes or glycoantigens.

Aims: To investigate the therapeutic effect of drug-loaded gemcitabine polybutylcyanoacrylate nanoparticles coupled with anti-human MUC1 monoclonal antibody (mAb) on human pancreatic cancer cell line and xenografts.

Settings and design: Randomized controlled trial.

Materials and methods: Gemcitabine-loaded nanospheres were prepared by emulsion polymerization; then, the anti-MUC1 mAb coupled with gemcitabine polybutylcyanoacrylate nanoparticles (MUC1-GEM-PBCA-NP) was prepared by chemical cross-linking. Cell-killing rates were detected by MTT assay in in vitro study, and changes in tumor cell cycle and apoptosis after treatment were detected by flow cytometry. Furthermore, in in vivo study, MUC1-GEM-PBCA-NP was injected into nude mice through the tail vein. Gemcitabine-loaded polybutylcyanoacrylate nanoparticles (GEM-PBCA-NP), gemcitabine bulk drug and empty nanoparticles (PBCA-NP), and normal saline blank control groups were established. Finally, data obtained were compared between groups.

Results: Compared with the control group, the cell-killing rate of each experimental group was significantly different (P < 0.05) in in vitro study, among which the MUC1-GEM-PBCA-NP group was significantly higher than other groups (P < 0.05). In addition, the apoptosis rate of the MUC1-GEM-PBCA-NP treatment group was significantly higher than that of other groups (P < 0.05). Furthermore, in in vivo study, the tumor inhibition rate of the MUC1-GEM-PBCA-NP treatment group was (68.14% ±1.66%), which was significantly higher than other control groups (P < 0.05). Finally, at the end of the treatment, the average tumor mass of the MUC1-GEM-PBCA-NP treatment group was (471.61 mg ± 12.16 mg), which was significantly lower than those of other control groups (P < 0.05).

Conclusions: MUC1-GEM-PBCA-NP could have an excellent inhibitory effect on tumors; thus, requiring further study.

Keywords: Gemcitabine; mucin 1; nanoparticles; pancreatic cancer.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Cell Line, Tumor
  • Deoxycytidine / analogs & derivatives
  • Gemcitabine
  • Humans
  • Mice
  • Mice, Nude
  • Mucin-1
  • Nanoparticles*
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / pathology

Substances

  • Antibodies, Monoclonal
  • Mucin-1
  • Deoxycytidine
  • Gemcitabine