Connecting Calcium-Based Nanomaterials and Cancer: From Diagnosis to Therapy

Abstract

As the indispensable second cellular messenger, calcium signaling is involved in the regulation of almost all physiological processes by activating specific target proteins. The importance of calcium ions (Ca2+) makes its “Janus nature” strictly regulated by its concentration. Abnormal regulation of calcium signals may cause some diseases; however, artificial regulation of calcium homeostasis in local lesions may also play a therapeutic role. “Calcium overload,” for example, is characterized by excessive enrichment of intracellular Ca2+, which irreversibly switches calcium signaling from “positive regulation” to “reverse destruction,” leading to cell death. However, this undesirable death could be defined as “calcicoptosis” to offer a novel approach for cancer treatment. Indeed, Ca2+ is involved in various cancer diagnostic and therapeutic events, including calcium overload-induced calcium homeostasis disorder, calcium channels dysregulation, mitochondrial dysfunction, calcium-associated immunoregulation, cell/vascular/tumor calcification, and calcification-mediated CT imaging. In parallel, the development of multifunctional calcium-based nanomaterials (e.g., calcium phosphate, calcium carbonate, calcium peroxide, and hydroxyapatite) is becoming abundantly available. This review will highlight the latest insights of the calcium-based nanomaterials, explain their application, and provide novel perspective. Identifying and characterizing new patterns of calcium-dependent signaling and exploiting the disease element linkage offer additional translational opportunities for cancer theranostics.

New anti-cancer explorations based on metal ions

“…Calcicoptosis mainly utilizes the retention and accumulation of calcium ions in tumor cells to cause persistent calcium overload, which interferes with or hinders tumor cell metabolism and proliferation, resulting in the cell malfunctioning and eventually inducing cell death [ 85 ]. Calcicoptosis has been applied to some calcium treatment cases [ 99 , 100 ]. However, the more specific mechanism remains to be further explored, and how to deliver calcium ions more efficiently and selectively to achieve a calcium overload state should be considered.…”

Recent Advances of Calcium Carbonate Nanoparticles for Biomedical Applications

“…The preparation of CaCO 3 NPs only needs common salts without organic solvents in most cases, which makes them low-cost [ 11 ]. Moreover, the surface of CaCO 3 NPs can be modified with targeted moiety, which promotes these CaCO 3 NPs to arrive at the target sites [ 12 ].…”

“…Because of the excellent biocompatibility/biodegradability, pH-sensitive property, ease of preparation and surface modification, CaCO 3 NPs have been widely used as carriers for a variety of treatments including chemical therapy [ 29 ], gene therapy [ 21 ], PTT/PDT [ 30 ] and combination therapy [ 31 ]. Moreover, CaCO 3 NPs themselves could be used as Ca 2+ generators which induce immunogenic cell death (ICD) and autophagy to activate immunotherapy [ 12 ].…”

A novel dual MoS2/FeGA quantum dots endowed injectable hydrogel for efficient photothermal and boosting chemodynamic therapy

“…In the presence of Fe 3+ and H + , H 2 O 2 could be decomposed and converted into highly active hydroxyl radicals, however, the spontaneous process of the reaction between Frontiers in Bioengineering and Biotechnology frontiersin.org endogenous Fe 3+ and H 2 O 2 is within the threshold of cellular redox homeostasis and cannot exert a therapeutic effect. In order to ensure the therapeutic effect (Luo et al, 2016;Min et al, 2020;Bai et al, 2022), it is urgent to inject exogenous Fenton's reagent to encourage excess hydroxyl radical formation in cancer cells. Thus, loading FeGA into hydrogels is expected to overcome this issue.…”