An Activatable Prodrug for the Treatment of Metastatic Tumors

被引:242
作者
Kim, Eun-Joong [1 ]
Bhuniya, Sankarprasad [1 ]
Lee, Hyunseung [1 ]
Kim, Hyun Min [1 ]
Cheong, Chaejoon [1 ,2 ]
Maiti, Sukhendu [3 ]
Hong, Kwan Soo [1 ,2 ]
Kim, Jong Seung [3 ]
机构
[1] Korea Basic Sci Inst, Div MR Res, Cheongju 363883, South Korea
[2] Univ Sci & Technol, Dept Bioanalyt Sci, Taejon 305350, South Korea
[3] Korea Univ, Dept Chem, Seoul 136701, South Korea
基金
新加坡国家研究基金会;
关键词
HYDROGEN-PEROXIDE; CANCER-CELLS; BIOMEDICAL APPLICATIONS; OXIDATIVE STRESS; DRUG-DELIVERY; THERAPY; LUNG; NANOPARTICLES; REPORTER; PROGRESS;
D O I
10.1021/ja5077684
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential antimetastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2 selectively inhibited tumor cell growth. Furthermore, intratracheally administered produrg 7 showed effective antitumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anticancer drug, SN-38.
引用
收藏
页码:13888 / 13894
页数:7
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