Combining Gemcitabine-Loaded Macrophage-like Nanoparticles and Erlotinib for Pancreatic Cancer Therapy

  • Mol Pharm. 2021 Jul 5;18(7):2495-2506. doi: 10.1021/acs.molpharmaceut.0c01225.
Hongqiao Cai  1 ,  Ruobing Wang  1 ,  Xingren Guo  1 ,  Meiyu Song  2 ,  Fei Yan  2 ,  Bai Ji  1 ,  Yahui Liu  1
Affiliations
  • 1. Department of Hepatobiliary and Pancreatic Surgery, the First Hospital, Jilin University, 71 Xinmin Street, Changchun 130021, China.
  • 2. State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), International Research Center for Chemistry-Medicine Joint Innovation, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.
PMID: 34078087 DOI: 10.1021/acs.molpharmaceut.0c01225
Abstract

Pancreatic Cancer is a lethal malignancy with a dismal prognosis. Gemcitabine is currently used to treat pancreatic Cancer, but it is limited by significant toxicity. Clinical trials on the combination of gemcitabine and erlotinib reported unsatisfactory outcomes along with concerns of toxicity. The encapsulation of chemotherapy drugs in polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) can alleviate toxicity through targeted delivery and sustained release. In addition, camouflaging the NPs with a macrophage membrane can evade the immune system and further improve tumor homing. We designed gemcitabine-loaded PLGA NPs with a macrophage membrane coating (MPGNPs) to reduce drug toxicity and increase the accumulation in the tumor. The combination of MPGNPs and erlotinib synergistically inhibited pancreatic Cancer cell proliferation in vitro and in vivo by targeting the PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways. The MPGNPs were also able to evade phagocytosis and achieve passive targeting to the pancreatic tumors. The combination of MPGNPs and erlotinib showed synergistic anti-tumor efficacy in vitro and in vivo. This study provides a proof-of-concept for treating pancreatic Cancer with a combination of MPGNPs and erlotinib.

Keywords
PLGA; erlotinib; gemcitabine; nanoparticles; pancreatic cancer.
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