Ion Interference Therapy of Tumors Based on Inorganic Nanoparticles

Abstract

As an essential substance for cell life activities, ions play an important role in controlling cell osmotic pressure balance, intracellular acid-base balance, signal transmission, biocatalysis and so on. The imbalance of ion homeostasis in cells will seriously affect the activities of cells, cause irreversible damage to cells or induce cell death. Therefore, artificially interfering with the ion homeostasis in tumor cells has become a new means to inhibit the proliferation of tumor cells. This treatment is called ion interference therapy (IIT). Although some molecular carriers of ions have been developed for intracellular ion delivery, inorganic nanoparticles are widely used in ion interference therapy because of their higher ion delivery ability and higher biocompatibility compared with molecular carriers. This article reviewed the recent development of IIT based on inorganic nanoparticles and summarized the advantages and disadvantages of this treatment and the challenges of future development, hoping to provide a reference for future research.

Keywords: cancer; inorganic nanoparticles; ion interference therapy; ions.

Figure 1

A schematic overview of ion interference antitumor therapy.

Figure 2

Schematic illustration of H⁺—induced antitumor therapy. The expansion of CaCO₃ nanoparticles will lead to lysosome expansion and the extrusion of a large amount of H⁺, resulting in intracellular acidification.

Figure 3

Schematic illustration of Na⁺—induced antitumor therapy. A large number of Na⁺ ions being released by NaCl nanoparticles in cancer cells leads to a change in cell osmotic pressure and further induces pyroptosis of cancer cells. Pyroptosis can promote the presentation efficiency of tumor-associated antigens to DCs, thus enhancing the antitumor immunity.

Figure 4

Schematic illustration of calcium overload-induced calcicoptosis. The overload of calcium ions in cancer cells promotes the damage of mitochondria, which induces specific calcium overload-induced cell death, which is called “calcicoptosis”.

Figure 5

Schematic illustration of Cl⁻—induced antitumor therapy. The released Cl⁻ by ClO₂, which can enter mitochondria through the voltage-dependent anion channel (VDAC), leads to mitochondrial damage and membrane potential decline, which further induce cell apoptosis.

Figure 6

Schematic illustration of Cu⁺—induced antitumor therapy. The released Cu²⁺ with the degradation of calcium phosphate in tumor cells can react with glutathione to form the Fenton agent Cu⁺, which further triggers the H₂O₂ to generate ⋅OH to enhance the antitumor effect.