乳铁蛋白
体内
化学
细胞毒性
药物输送
肿瘤微环境
癌症研究
血管生成
靶向给药
癌细胞
癌症
药理学
体外
肿瘤细胞
生物化学
医学
生物
内科学
生物技术
有机化学
作者
Tongfu Yang,Zhenlei Zhang,Juzheng Zhang,Yanping Li,Wenjuan Li,Hong Liang,Feng Yang
标识
DOI:10.1021/acs.jmedchem.2c01684
摘要
To develop a next-generation anticancer metal-based drug, realize the multi-targeted combination therapy of protein drug and metal-based drug for cancer, solve their co-delivery challenges, and improve their in vivo targeting ability, we proposed to develop a multi-targeted anticancer metal-based agent exploiting the properties of the tumor microenvironment (TME) and of lactoferrin (LF). To this end, we optimized a series of gallium (Ga, III) isopropyl-2-pyridyl-ketone thiosemicarbazone compounds to obtain a Ga compound (C4) with remarkable cytotoxicity and then constructed a new LF-C4 nanoparticle (LF-C4 NP) delivery system. In vivo studies showed that LF-C4 NPs not only had a greater capacity for inhibiting tumor growth than LF or C4 alone but also solved the co-delivery problems of LF and C4 and improved their targeting ability. Furthermore, free C4 and LF-C4 NPs inhibited tumor growth through multiple synergistic actions on the TME: killing cancer cell, inhibiting tumor angiogenesis, and activating immune system.
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