Abstract
Abstract
Background
Calcium ions (Ca2+) participates in various intracellular signal cascades and especially plays a key role in pathways relevant to cancer cells. Mitochondrial metabolism stimulated by calcium overload can trigger the opening of the mitochondrial permeability transition pore (MPTP), which leads to cancer cell death.
Methods
Herein, a mitochondrial pathway for tumour growth inhibition was built via the double-activation of MPTP channel. Fe2+ doped covalent organic frameworks (COF) was synthesised and applied as template to grow CaCO3 shell. Then O2 was storaged into Fe2+ doped COF, forming O2-FeCOF@CaCO3 nanocomposite. After modification with folic acid (FA), O2-FeCOF@CaCO3@FA (OFCCF) can target breast cancer cells and realize PDT/Ca2+ overload synergistic treatment.
Results
COF can induce the production of 1O2 under 650 nm irradiation for photodynamic therapy (PDT). Low pH and hypoxia in tumour microenvironment (TME) can activate the nanocomposite to release oxygen and Ca2+. The released O2 can alleviate hypoxia in TME, thus enhancing the efficiency of COF-mediated PDT. Abundant Ca2+ were released and accumulated in cancer cells, resulting in Ca2+ overload. Notably, the reactive oxygen species (ROS) and Ca2+ overload ensure the sustained opening of MPTP, which leads to the change of mitochondria transmembrane potential, the release of cytochrome c (Cyt c) and the activation of caspases 3 for cancer cell apoptosis.
Conclusion
This multifunctional nanosystem with TME responded abilities provided a novel strategy for innovative clinical cancer therapy.
Graphical Abstract
Funder
National Natural Science Foundation of China
Science and Technology Development Planning Project of Jilin Province
Publisher
Springer Science and Business Media LLC
Subject
Pharmaceutical Science,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,Medicine (miscellaneous),Bioengineering
Reference48 articles.
1. Monteith GR. Prostate cancer cells alter the nature of their calcium influx to promote growth and acquire apoptotic resistance. Cancer Cell. 2014;26(1):1–2.
2. Cui C, Merritt R, Fu L, Pan Z. Targeting calcium signaling in cancer therapy. Acta Pharm Sin B. 2017;7(1):3–17.
3. Várnai GP, Golenár T, Roy S, Purkins G, Schneider TGT, Balla G. Hajnóczky, imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface Molr. Cell. 2010;39(1):121–32.
4. Parkash J, Asotra K. Calcium wave signaling in cancer cells. Life Sci. 2010;87(19–22):587–95.
5. Lyu Y, Xie C, Chechetka SA, Miyako E, Pu K. Semi-conducting polymer nanobioconjugates for targeted photothermal activation of neurons. J Am Chem Soc. 2016;138(29):9049–52.
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