Cai Hongqiao, Wang Ruobing, Guo Xingren, Song Meiyu, Yan Fei, Ji Bai, Liu Yahui
Department of Hepatobiliary and Pancreatic Surgery, the First Hospital, Jilin University, 71 Xinmin Street, Changchun 130021, China.
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.
Mol Pharm. 2021 Jul 5;18(7):2495-2506. doi: 10.1021/acs.molpharmaceut.0c01225. Epub 2021 Jun 2.
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--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 and 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 and . This study provides a proof-of-concept for treating pancreatic cancer with a combination of MPGNPs and erlotinib.
胰腺癌是一种预后极差的致命恶性肿瘤。吉西他滨目前用于治疗胰腺癌，但受到显著毒性的限制。关于吉西他滨与厄洛替尼联合使用的临床试验报告结果不尽人意，且存在毒性问题。将化疗药物包裹在聚乳酸-乙醇酸（PLGA）纳米颗粒（NPs）中可通过靶向递送和缓释减轻毒性。此外，用巨噬细胞膜伪装纳米颗粒可逃避免疫系统并进一步改善肿瘤归巢。我们设计了具有巨噬细胞膜涂层的载吉西他滨PLGA纳米颗粒（MPGNPs），以降低药物毒性并增加肿瘤中的蓄积。MPGNPs与厄洛替尼联合通过靶向PI3K/AKT/mTOR和Ras/Raf/MEK/ERK信号通路协同抑制胰腺癌细胞增殖。MPGNPs还能够逃避吞噬作用并实现对胰腺肿瘤的被动靶向。MPGNPs与厄洛替尼联合显示出协同抗肿瘤疗效。本研究为用MPGNPs与厄洛替尼联合治疗胰腺癌提供了概念验证。
