Recent Advances in Calcium‐Based Anticancer Nanomaterials Exploiting Calcium Overload to Trigger Cell Apoptosis

• Published in: Advanced functional materials Vol. 33; no. 3
• Main Authors: Xiao, Yupeng, Li, Zhao, Bianco, Alberto, Ma, Baojin
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01-01-2023; Wiley
• Subjects: Apoptosis; Ca 2+ channels; Calcium carbonate; Calcium ions; calcium phosphate nanoparticles; Calcium phosphates; Cancer therapies; cell uptake; Chemical Sciences; Damage tolerance; Efflux; Endoplasmic reticulum; Materials science; Medicinal Chemistry; Mitochondria; Nanomaterials; Optimization; Overloading; oxidative stress; Signal transduction; calcium phosphate nanoparticles; Ca2+ channels; oxidative stress; endoplasmic reticulum; cell uptake
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.202209291

Calcium ion is vital for the regulation of many cellular functions and serves as a second messenger in the signal transduction pathways. Once the intracellular Ca2+ level exceeds the tolerance of cells (called Ca2+ overload), oxidative stress, mitochondrial damage, and cell/mitochondria apoptosis happen. Therefore, Ca2+ overload has started to be deeply exploited as a new strategy for cancer therapy due to its high efficiency and satisfactory safety. This review aims to highlight the recent development of Ca2+‐based nanomaterials (such as Ca3(PO4)2, CaCO3, CaO2, CaH2, CaS, and others) able to trigger intracellular Ca2+ overload and apoptosis in cancer therapy. The intracellular mechanisms of varied Ca2+‐based nanomaterials and the different types of strategies to enhance Ca2+ overload are discussed in detail. Moreover, the design of more efficient Ca2+ overload‐mediated cancer therapies is prospected mainly based on 1) the enhanced cellular uptake by surface modification and morphology optimization of nanomaterials, 2) the accelerated Ca2+ release from nanomaterials by increasing the intracellular H+ level and by photothermal effect, and 3) the overload maintenance by Ca2+ efflux inhibition, Ca2+ influx promotion, or promoting Ca2+ release from the endoplasmic reticulum.
This review aims to highlight the recent development of Ca2+‐based nanomaterials able to trigger intracellular Ca2+ overload and apoptosis in cancer therapy. The intracellular mechanisms of varied Ca2+‐based nanomaterials and the different types of strategies to enhance Ca2+ overload are discussed in detail. Moreover, the design of more efficient Ca2+ overload‐mediated cancer therapies is prospected.