期刊
NANOMATERIALS
卷 12, 期 21, 页码 -出版社
MDPI
DOI: 10.3390/nano12213767
关键词
platinum(IV) conjugates; cisplatin; phenolic acid; nanoparticles; drug delivery; breast cancer
类别
资金
- program FEM POWER - operational program ESF Saxony-Anhalt WISSENSCHAFT Chancengleichheit)
- program FEM POWER (European Union)
- Graduate School Building with Molecules and Nanoobjects (BuildMoNa)
- Research Academy Leipzig
- Ministry of Education, Science and Technological Development of the Republic of Serbia [451-03-68/2022-14/200007]
Platinum(IV) conjugates based on a cisplatin scaffold containing derivatives of caffeic and ferulic acid demonstrated higher or comparable activity with respect to cisplatin against different human breast cancer cell lines, while showing superior antiproliferative activity upon immobilization in mesoporous silica nanoparticles. Mechanistic investigations revealed that these compounds induce apoptotic cell death causing strong caspase activation in a mouse breast cancer cell line.
The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin include drug resistance and significant side effects. Due to their better stability, as well as the possibility to introduce biologically active ligands in their axial positions constructing multifunctional prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations. Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV) conjugates demonstrated higher or comparable activity with respect to cisplatin against different human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1), and the corresponding MSNs (SBA-15|1) in a 4T1 mouse breast cancer cell line showed that these compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice, 1 and SBA-15|1 inhibited the tumor growth while decreasing the necrotic area and lowering the mitotic rate.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据