胸苷磷酸化酶
肿瘤微环境
下调和上调
癌症研究
化学
癌细胞
分泌物
胸苷
CD8型
细胞生物学
生物
癌症
生物化学
免疫学
免疫系统
医学
肿瘤细胞
内科学
酶
基因
DNA
作者
Yan Peng,Yumiao Hu,Liyan Qiu
标识
DOI:10.1016/j.nano.2021.102501
摘要
On the basis of immuno-modulating effect and upregulating the activity of thymidine phosphorylase (TP), interferon-γ (IFN-γ) as a cooperative attacker was explored to enhance the anticancer activity of 5-fluorouracil (5-FU). We designed and prepared a self-assembled nano-vesicular system IFN-γ-EDP formulated by amphiphilic poly((polyethylene glycol)(dodecylphosphoethanolamine)phosphazene) (EDP) to entrap IFN-γ in the hydrophilic cavity. The IFN-γ-EDP vesicles allowed IFN-γ to accumulate at the tumor site and be taken up by tumor cells, resulting in significantly upregulated expression level of TP, distinct inhibition of cell growth, more cellular apoptosis and more serious cell cycle arrest when administrated combined with 5-FU. Moreover, IFN-γ-EDP could normalize the tumor microenvironment by enhancing the CD4+ and CD8+ T cell populations, promoting the IL-12 secretion and suppressing the IL-10 secretion in tumor. As a consequence, the combination therapy of IFN-γ-EDP with 5-FU achieved remarkably enhanced tumor inhibition rate of 56.9% against CT26 colorectal cancer.
科研通智能强力驱动
Strongly Powered by AbleSci AI