Co-delivery of gemcitabine and Mcl-1 SiRNA via cationic liposome-based system enhances the efficacy of chemotherapy in pancreatic cancer

Yanbing Wang, Fenghua Gao, Xingwei Jiang, Xiao Zhao, Yu Wang, Qiyuan Kuai, Guangjun Nie, Min He, Yingjie Pan, Wei Shi, Suping Ren, Qun Yu

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Myeloid cell leukemia 1 (Mcl-1) overexpression is found in various human tumors and has emerged as a promising new target for pancreatic cancer treatment. Recent research has found that most pancreatic cancers develop resistance to the current first-line chemotherapeutic drug, gemcitabine (Gem), and high expression of Mcl-1 can reduce the sensitivity of pancreatic cancer cells to Gem chemotherapy. Therefore, novel strategies, such as combination therapy, to overcome resistance of Gem chemotherapy are needed urgently. Here, we employed a lipid-based delivery system (LPs) to codeliver Mcl-1 siRNA and Gem for pancreatic cancer treatment, named LP-Gem-siMcl-1. LP-Gem-siMcl-1 exhibited an increased cellular uptake, enhanced Mcl-1 down-regulation efficacy, and significant cytotoxicity in the human pancreatic carcinoma cell lines PANC-1 and BxPC-3. Furthermore, tumor inhibition in vivo proved that LP-Gem-siMcl-1 has higher anti-tumor efficiency than LP-siMcl-1 plus LP-Gem, indicating the synergistic anti-tumor effects of Gem and siMcl-1. Meanwhile, histological analysis demonstrated that LPs could efficiently co-deliver Gem and Mcl-1 siRNA to cancerous cells and overcome the resistance of Gem. Taken together, our results offer proof that LP-Gem-siMcl-1 is an effective co-delivery system to treat pancreatic cancers and may serve as a valuable tool for developing new strategies for cancer therapy.

Original languageEnglish (US)
Pages (from-to)966-978
Number of pages13
JournalJournal of Biomedical Nanotechnology
Volume15
Issue number5
DOIs
StatePublished - May 2019

Keywords

  • Gemcitabine
  • Myeloid cell leukemia 1
  • Nanoparticles
  • Pancreatic cancer
  • RNA interference

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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