Dual-Responsive Turn-on T 1 Imaging-Guided Mild Photothermia for Precise Apoptotic Cancer Therapy.
Sijie SongQi WangJiangao XieJunduan DaiDilan OuyangGuoming HuangYuheng GuoChen ChenMengnan WuTingjing HuangJingwen RuanXiaofeng ChengXucong LinYu HeElena A RozhkovaZhaowei ChenHuang-Hao YangPublished in: Advanced healthcare materials (2023)
Apoptosis has gained increasing attention in cancer therapy as an intrinsic signaling pathway, which leads to minimal leakage of waste products from a dying cell to neighboring normal cells. Among various stimuli to trigger apoptosis, mild hyperthermia is attractive but confronts limitations of non-specific heating and acquired resistance from elevated expression of heat shock proteins. Here, we develop a dual-stimulation activated turn-on T 1 imaging-based nanoparticulate system (DAS) for mild photothermia (∼43°C)-mediated precise apoptotic cancer therapy. In the DAS, a superparamagnetic quencher (ferroferric oxide nanoparticle, Fe 3 O 4 NP) and a paramagnetic enhancer (Gd-DOTA complex) are connected via the N6-methyladenine (m 6 A)-caged, Zn 2+ -dependent DNAzyme molecular device. When the nanodevice is taken up by cancer cells, overexpressed fat mass and obesity-associated protein (FTO) specifically demethylates the m 6 A group, thereby activating DNAzymes to cleave the substrate strand and simultaneously releasing Gd-DOTA complex-labeled and HSP70-inhibiting oligonucleotides. The restored T 1 signal from the liberated Gd-DOTA complexes lights up the tumor to guide the location and time of deploying 808 nm laser irradiation. Afterwards, locally generated mild photothermia works in concert with HSP70 antisense oligonucleotides to promote apoptosis of tumor cells. This highly integrated design provides an alternative strategy for mild hyperthermia-mediated precise apoptotic cancer therapy. This article is protected by copyright. All rights reserved.
Keyphrases
- cancer therapy
- cell death
- cell cycle arrest
- heat shock
- signaling pathway
- drug delivery
- pi k akt
- pet imaging
- pet ct
- induced apoptosis
- endoplasmic reticulum stress
- oxidative stress
- heat shock protein
- heat stress
- high resolution
- living cells
- heavy metals
- type diabetes
- poor prognosis
- metabolic syndrome
- anti inflammatory
- sensitive detection
- palliative care
- insulin resistance
- weight loss
- photodynamic therapy
- working memory
- binding protein
- epithelial mesenchymal transition
- rheumatoid arthritis
- computed tomography
- risk assessment
- mesenchymal stem cells
- mass spectrometry
- body mass index
- systemic lupus erythematosus
- single molecule
- quantum dots
- bone marrow
- radiation therapy
- radiation induced