期刊
ACS APPLIED NANO MATERIALS
卷 4, 期 1, 页码 198-210出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsanm.0c02521
关键词
platinum nanoparticles; doxorubicin; breast cancer; apoptosis; PI3K/AKT signaling
资金
- Science Engineering and Research Board (SERB), New Delhi, India [ECR/2016/001456]
- RUSA. Phase 2.0 grant [F. 24-51/2014U]
- USIC, Alagappa University
- Imaging Probe Development Platform, Lee Kong Chian School of Medicine, Nanyang Technological University (NTU)
- NTU-Austrian Institute of Technology and Medical University of Vienna Internal Grant, Singapore [NAM/15006]
- Indian Council of Medical Research (ICMR), New Delhi
This study reports a theranostic platinum nanoparticle platform conjugated with an anticancer drug, which induces apoptosis in breast cancer cells by activating a specific signaling pathway. These findings suggest that this platform may serve as a promising agent for cancer nanomedicine.
Herein, we report facile theranostic platinum nanoparticles (PtNPs) conjugated to an anticancer drug, doxorubicin (DOX), in unraveling the inhibition of a cell survival PI3K/AKT (phosphatidylinositol 3-kinase/protein kinase B) signaling pathway in MCF-7 and MDA-MB-231 human breast cancer cells. The significant features of our DOX@PtNPs as a theranostic platform are as follows: (i) drug release studies showed a progressive pH-dependent delivery; (ii) in vitro studies of pox@PtNPs displayed a relatively higher cytotoxicity to breast cancer cells compared to unconjugated PtNPs and DOX; (iii) intracellular drug release studies showed a specific binding of DOX@PtNPs and their release within the cytoplasm and perinuclear region; (iv) DOX@PtNPs induced the apoptosis of cancer cells by DNA damage via the generation of elevated levels of reactive oxygen species and decreased mitochondrial membrane potential (Delta Psi(m)), as evidenced by fluorescence microscopic studies; and (v) DOX@PtNPs inhibited the PI3K/AKT signaling pathway in breast cancer cells by activating PTEN, a tumor suppressor gene. The induced mitochondrial-dependent apoptotic pathway led to the activation of downstream caspases. Finally, our findings illustrate that DOX@PtNPs may serve as a better theranostic agent for cancer nanomedicine.
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