Nitric Oxide Modulating Calcium Store for Ca²⁺‐Initiated Cancer Therapy

Abstract

Ions are essential to body, but sometimes can evolve into weapons to attack and destroy cells without systematic toxicity and drug resistance. Inspired by nitric oxygen as neurotransmitter in mediating Ca2+ release, NO nanodonors with high photoreactivity and stability are constructed with upconversion nanoparticles (UCNPs) coated by zeolitic nitro‐/nitrile‐imidazole framework‐82 (ZIF‐82), capable of near‐infrared light (NIR) triggered NO generation and berbamine (BER) release, to achieve cancer therapy with the stored Ca2+ in cells. The spatial confinement effect of 2‐nitroimidazole in ZIF‐82 enables NO‐releasing with tunable release kinetics. NO turns on the ryanodine receptors overexpressed in cancer cells for abrupt Ca2+ elevation; meanwhile, berbamine (BER) turns Ca2+‐excretion pumps off to inhibit calcium efflux, resulting in intracellular Ca2+ overload induced apoptosis. This work provides the first example of regulating endogenous ions for cell killing, which holds promise as an effective cancer therapeutics that is complementary to traditional chemotherapeutics.

Recent advances in upconversion nanoparticle-based nanocomposites for gas therapy

“…2f). 53 The diffused NO as antibacterial, tissues/nerve protection, and regeneration. [54][55][56] NO shows broad-spectrum anti-bacterial activity while avoiding antimicrobial resistance, and it has aroused wide interests in the treatment of various bacterial infections.…”

“…52 f) Intracellular calcium stores modulated by NO for Ca 2+ -initiated cancer therapy. 53 Adapted from Ref. [48] with permission from Wiley-VCH, copyright 2012; adapted from Ref.…”

“…[52] with permission from American Chemical Society, copyright 2020; adapted from Ref. [53] with permission from Wiley-VCH, copyright 2021. 29 Adapted from Ref.…”

Ion Interference Therapy of Tumors Based on Inorganic Nanoparticles

“…Ions exist widely in the human body and have always been the focus of research due to their participation in various life activities, including osmotic pressure, the acid–base balance, catalytic and signal pathway activation, the protein and enzyme composition, targeting biomolecules and so on [ 5 ]. The abnormal distribution or specific accumulation of some metal or non-metal ions in cells cause irreversible damage to cells or activate cytotoxicity-related biochemical reactions to induce cell death, which provides a new method for tumor therapy, namely ion interference therapy [ 6 ].…”

Phytic acid-modified CeO2 as Ca2+ inhibitor for a security reversal of tumor drug resistance

“…With the rapid development of nanoscience and nanotechnology in modern medicine, nanomaterials have shown their great potentials to improve human living standards as well as disease therapy [13][14][15][16][17][18][19][20][21][22][23]. Specifically, nanomaterials have been designed to greatly overload the intracellular Ca 2+ levels for tumor therapy [22][23][24].…”