College of Biotechnology and Bioengineering, Zhejiang University of Technology, 310032, Hangzhou, China.
Macromol Biosci. 2017 Dec;17(12). doi: 10.1002/mabi.201700273. Epub 2017 Nov 13.
Polymeric nanoparticles gain enormous interests in cancer therapy. Polyethylenimine (PEI) 25 kD is well known for its high transfection efficiency and cytotoxicity. PEI-CyD (PC) was previously synthesized by conjugating low molecular PEI (M 600) with β-cyclodextrin (β-CyD), which is shown to induce lower cytotoxicity than PEI 25 kD. In the current study, the in vivo immune response of branched PEI 25 kD and PC is investigated. Compared to PC/pDNA, exposure of PEI 25kD/pDNA induces higher level of immune-stimulation evidenced by the increased spleen weight, phagocytic capacity of peritoneal macrophage, and proinflammatory cytokines in serum and liver. Importantly, administration of PEI 25 kD can greatly promote breast cancer metastasis in liver and lung tissues, which correlates with its ability to induce high oxidative stress and NLRP3-inflammasome activation. These results suggest that polymeric nanocarriers have the potential to induce immune-stimulation and cancer metastasis, which may affect their efficiency for cancer therapy.
聚合物纳米颗粒在癌症治疗中引起了极大的兴趣。聚乙稀亚胺（PEI）25kDa 因其高转染效率和细胞毒性而广为人知。PEI-CyD（PC）是通过将低分子量的 PEI（M600）与β-环糊精（β-CyD）连接合成的，其显示出比 PEI25kDa 更低的细胞毒性。在本研究中，研究了支化 PEI25kD 和 PC 的体内免疫反应。与 PC/pDNA 相比，PEI25kD/pDNA 的暴露会引起更高水平的免疫刺激，这表现在脾重增加、腹腔巨噬细胞的吞噬能力以及血清和肝脏中的促炎细胞因子增加。重要的是，PEI25kD 的给药可以极大地促进乳腺癌在肝和肺组织中的转移，这与其诱导高氧化应激和 NLRP3-炎症小体激活的能力有关。这些结果表明，聚合物纳米载体有可能引起免疫刺激和癌症转移，这可能会影响它们用于癌症治疗的效率。
