Nanoparticle-Mediated Therapeutic Application for Modulation of Lysosomal Ion Channels and Functions

Abstract

Applications of nanoparticles in various fields have been addressed. Nanomaterials serve as carriers for transporting conventional drugs or proteins through lysosomes to various cellular targets. The basic function of lysosomes is to trigger degradation of proteins and lipids. Understanding of lysosomal functions is essential for enhancing the efficacy of nanoparticles-mediated therapy and reducing the malfunctions of cellular metabolism. The lysosomal function is modulated by the movement of ions through various ion channels. Thus, in this review, we have focused on the recruited ion channels for lysosomal function, to understand the lysosomal modulation through the nanoparticles and its applications. In the future, lysosomal channels-based targets will expand the therapeutic application of nanoparticles-associated drugs.

The Toxicity of Polystyrene-Based Nanoparticles in Saccharomyces cerevisiae Is Associated with Nanoparticle Charge and Uptake Mechanism

“…However, biopersistent nanomaterials may conversely affect the autophagy and endolysosomal pathways, which would result in a lysosomal dysfunction and toxicity to the cells . Several nanoparticles have been shown to cause lysosomal degradation and to situate themselves in the lysosomal compartment inside the cell . On the one hand, exposure to Ag NPs, Au NPs, and rare-earth oxide nanoparticles (REO NPs) causes an alkalization of the lysosomal lumen .…”

“…Several nanoparticles have been shown to cause lysosomal degradation and to situate themselves in the lysosomal compartment inside the cell . On the one hand, exposure to Ag NPs, Au NPs, and rare-earth oxide nanoparticles (REO NPs) causes an alkalization of the lysosomal lumen . Exposure to silica dioxide (SiO 2 ) NPs, Gd 2 O 3 :Eu 3+ (Gd 2 O 3 ) NPs, polystyrene nanoparticles (PS NPs), and TiO 2 NPs, on the other hand, damages the lysosomes and induces cell death .…”

The acetone crude extract of Quercus infectoria (Olivier) galls alters pH of the digestive vacuole of the malaria parasite, Plasmodium falciparum

“…Many studies described that the malaria parasite death by artemisinin treatment was associated with the altered pH of the digestive vacuole (Abu-Bakar et al, 2013;Ibrahim et al, 2020;. Subtle pH changes in other acidic organelles such as lysosomes (increase by 0.1-0.2 units) are known to cause a significant decrease in the lysosomal enzyme activity involved in the digestion process, eventually causing numerous pathological alterations (Xu & Ren, 2015;Colacurcio & Nixon, 2016;Lee & Hong, 2020). In addition, an increase in lysosomal pH could reduce the lysosomal degradation capacity and block autophagosome and endocytic maturation (Lee & Hong, 2020).…”

“…Subtle pH changes in other acidic organelles such as lysosomes (increase by 0.1-0.2 units) are known to cause a significant decrease in the lysosomal enzyme activity involved in the digestion process, eventually causing numerous pathological alterations (Xu & Ren, 2015;Colacurcio & Nixon, 2016;Lee & Hong, 2020). In addition, an increase in lysosomal pH could reduce the lysosomal degradation capacity and block autophagosome and endocytic maturation (Lee & Hong, 2020). Evidence has also shown that the depletion of parasite ATP through energy source removal required to pump H + altered the digestive vacuole and subsequently alkalized (Collins & Forgac, 2018;Pamarthy et al, 2018).…”

Antagonistic cytoprotective effects of C60 fullerene nanoparticles in simultaneous exposure to benzo[a]pyrene in a molluscan animal model

“…Of concern also are the higher level consequences for damage to animal health, associated ecological risk and the possible food chain risks for humans. The lysosomal vacuolar system in the cells of the molluscan digestive gland (hepatopancreas or midgut gland) readily accumulates many harmful environmental contaminants, including metal ions, organic xenobiotics, nano-and micro-plastics and other nanomaterials (Barranger et al, 2019a, b;Jimeno-Romero et al, 2016;Koehler et al, 2008, Lee & Hong, 2020Moore et al2004;Sforzini et al, 2018, 2020, Shaw et al, 2019Von Moos et al, 2012). Lysosomal overload due to sequestration J o u r n a l P r e -p r o o f and accumulation of non-degradable foreign materials (e.g., nanomaterials) and xenobiotic chemicals (e.g., metal ions and organic chemical contaminants) can lead to lysosomal and autophagic dysfunction, involving permeabilisation of the lysosomal membrane and in severe cases release of lysosomal enzymes and cell death (De Duve et al, 1974;Moore et al, 2006, 2007, Sforzini et al, 2018, 2020Shaw et al, 2019;Stern et al, 2012).…”