In Search of a Converging Cellular Mechanism in Nanotoxicology and Nanomedicine in the Treatment of Cancer

Abstract

Multiple applications of nanomaterials have raised concern with regard to their toxicity. With increasing research into nanomaterial safety, mechanisms involved in the toxic effects of nanomaterials have begun to emerge. The importance of nanomaterial-induced lysosomal membrane permeabilization through overloading or direct damage of the lysosomal compartment, resulting in the blockade of autophagosome-lysosome fusion and autophagy dysfunction, as well as inflammasome activation were cited as emerging mechanisms of nanomaterial toxicity. It has recently been proposed that these very mechanisms leading to nanomaterial toxicity may be utilized in nanotherapeutics. This review discusses these nanomaterial-induced mechanisms in detail and how it has been exploited in cancer research. This review also addresses certain considerations that need to be kept in mind when using nanomaterials in therapeutics.

Silver nanoparticles regulate autophagy through lysosome injury and cell hypoxia in prostate cancer cells

“…[ 38 ] At present, many studies reported that engineered nanomaterials could result in lysosomal dysfunction and cause autophagy processes under a toxic dose. [ 39,40 ] Moreover, several research works also suggested that AgNPs could give rise to autophagy in different conditions. [ 41,42 ] However, more investigations should be made to explain the autophagic regulation by AgNPs under sublethal dose.…”

Understanding Nanoparticle Toxicity to Direct a Safe-by-Design Approach in Cancer Nanomedicine

“…The key mechanisms of pinocytosis, which are involved in nanoparticle uptake include micropinocytosis, clathrin-mediated endocytosis, caveolae-mediated endocytosis, and clathrin-and caveolae-independent endocytosis [158]. Ultimately, most of their endocytic pathways lead to contents ending up in lysosomes for degradations [159]. However, in caveolae-mediated endocytosis, from endosomes, the contents form caveosomes, which are transported to the endoplasmic reticulum/Golgi apparatus, avoiding lysosomal degradation.…”

“…However, in caveolae-mediated endocytosis, from endosomes, the contents form caveosomes, which are transported to the endoplasmic reticulum/Golgi apparatus, avoiding lysosomal degradation. This nuance in the uptake mechanisms was discovered as an important consideration for tailoring nanocarriers with drugs in cancer therapy [159].…”

Intracellular and extracellular targets as mechanisms of cancer therapy by nanomaterials in relation to their physicochemical properties

“…Similarly, Song, Du, Feng, Wu, and Yan (2013) demonstrated the induction of pyroptosis by ZnO NPs via the caspase‐1 pathway in A549 lung cancer cells. The importance of NM‐induced pyroptosis in immunotherapy is scarce and it has been suggested that the toxicological mechanisms of NMs involving LMP, inflammasome activation, and pyroptosis be considered as a potential research area in cancer therapy (Gulumian & Andraos, 2018). Indeed, LMP could activate pyroptosis via caspase‐1 and NLRP3 inflammasome activation (Repnik, Česen, & Turk, 2014).…”