Journal
MOLECULAR PHARMACEUTICS
Volume 18, Issue 7, Pages 2495-2506Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.0c01225
Keywords
PLGA; gemcitabine; erlotinib; pancreatic cancer; nanoparticles
Funding
- National Natural Science Foundation of China (NSFC) [81802805]
- Jilin Province Health Technology Innovation Project [2017J047]
- Jilin Province Medical Scientist Fund Project [3D5197909428]
- Natural Science Foundation of Jilin Province [20200201417JC, 20200201490JC]
- Translation-Clinical Joint Foundation of the First Hospital of Jilin University [2020-ZL-04]
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The combination of gemcitabine-loaded PLGA nanoparticles with a macrophage membrane coating showed promising results in reducing drug toxicity, improving tumor accumulation, and inhibiting pancreatic cancer cell proliferation through targeting signaling pathways. This approach provides potential synergistic anti-tumor efficacy for treating pancreatic cancer.
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.
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