{"id":249,"date":"2020-03-25T12:29:05","date_gmt":"2020-03-25T12:29:05","guid":{"rendered":"http:\/\/www.cd-bioparticles.net\/blog\/?p=249"},"modified":"2023-08-02T07:59:51","modified_gmt":"2023-08-02T07:59:51","slug":"the-mystery-of-cationic-nanocarrier-toxicity","status":"publish","type":"post","link":"https:\/\/www.cd-bioparticles.net\/blog\/the-mystery-of-cationic-nanocarrier-toxicity\/","title":{"rendered":"The Mystery Of Cationic Nanocarrier Toxicity"},"content":{"rendered":"

With the application of nanotechnology in the field of medicine, lipid- or polymer-based nanocarriers are becoming the mainstream for delivering small-molecule drugs and large molecules, which has increased the effectiveness of drugs and simplified their administration.\u00a0Nano-scale carriers not only The advantages of nanomaterials, as well as novel properties and functions, such as the ability to interact with complex cell functions in new ways, can create new biomedical applications.\u00a0In addition, by designing physicochemical properties or surface modification, nanocarriers have multiple potentials for targeted drug delivery to specific sites.\u00a0Among them, surface charge is one of the important characteristics of nanoparticles.\u00a0Positively-charged nanocarriers formed from cationic lipids or polymers are most commonly used in gene delivery as non-viral vectors, including cationic liposomes, polyethyleneimine (PEI), chitosan, and the like.\u00a0Due to the positively charged surface, cationic nanocarriers can simply load and concentrate nucleic acids by interacting with anionic nucleic acid cargo.\u00a0Compared with viral vectors, cationic nanocarriers also have other advantages, such as simplicity in large-scale production and less stringent vector size restrictions.\u00a0Although the benefits of nanocarriers in drug delivery have drawn widespread attention, toxicity has been a major obstacle in the application of cationic carriers. As nanocarriers of drug delivery systems (DDS) have been introduced into the human body, their toxicity has caused increasing public health concern.<\/p>\n

In research related to the preclinical or clinical use of cationic nanocarriers, researchers have discovered potential adverse effects due to cell and tissue interactions and the immunostimulation of nanocarriers.\u00a0Even the most widely used liposome complexes are limited due to the occurrence of toxicity such as inflammatory toxicity, liver toxicity, leukopenia, and thrombocytopenia.\u00a0It has been reported that cationic carriers such as liposomes and PEI accumulate in the lungs immediately after administration.\u00a0The lung’s inflammatory response is observed after several hours of topical application of the lipid plexus (atomization or intratracheal perfusion).<\/p>\n

Further research found that necrosis is one of the factors that cause this inflammatory response.\u00a0Necrosis is traditionally considered to be the accidental or passive type of cell death caused by non-physiological stress.\u00a0However, some recent evidence suggests that the execution of necrotic cell death can be regulated by a set of signal transduction pathways.\u00a0It is assumed that necrotic cells release endogenous molecules.\u00a0This hypothetical form of damage is called damage-associated molecular patterns (DAMPs).\u00a0Previous studies have found that mitochondria in the body can function as a major source of DAMP.\u00a0For example, mitochondrial DNA (mtDNA) has been reported to induce an inflammatory response after injury.\u00a0It is conceivable that the inflammatory response induced by cationic nanocarriers may be related to cell death and subsequent release of DAMPs, which in turn chemotactic and activate inflammatory cells.\u00a0To test this concept, the researchers conducted further exploration.<\/p>\n

\"\"
Figure 1. The structure of Na+\/K+-ATPase-DOTAP.<\/figcaption><\/figure>\n

It was found that injection of cationic nanocarriers (including cationic liposomes, PEI, and chitosan) could lead to the rapid appearance of necrotic cells.\u00a0Treatment with cationic nanocarriers inhibited Na + \/ K + -ATPase activity in vitro and in vivo, causing intracellular Na + overload with cell death.\u00a0The ability of cationic nanocarriers to induce cell necrosis depends on their positive surface charge.\u00a0Further analysis showed that cell necrosis induced by cationic nanocarriers and the resulting leakage of mitochondrial DNA can cause severe inflammation in the body, which is mediated by pathways involving TLR9 and MyD88 signaling.\u00a0therefore.\u00a0It can be determined that cationic nanocarriers induce acute cell necrosis through the interaction with Na + \/ K + -ATPase, and subsequent exposure of molecular patterns related to mitochondrial damage is a key event that mediates the inflammatory response.<\/p>\n","protected":false},"excerpt":{"rendered":"

With the application of nanotechnology in the field of medicine, lipid- or polymer-based nanocarriers are becoming the mainstream for delivering small-molecule drugs and large molecules, which has increased the effectiveness of drugs and simplified their administration.\u00a0Nano-scale carriers not only The advantages of nanomaterials, as well as novel properties and functions, such as the ability to interact with complex cell functions in new ways, can create new biomedical applications.\u00a0In addition, by designing physicochemical properties or surface modification, nanocarriers have multiple potentials for targeted drug delivery to specific sites.\u00a0Among them, surface charge is one of the important characteristics of nanoparticles.\u00a0Positively-charged nanocarriers formed from cationic lipids or polymers are most commonly used in gene delivery as non-viral vectors, including cationic liposomes, polyethyleneimine (PEI), chitosan, and the like.\u00a0Due to the positively charged surface, cationic nanocarriers can simply load and concentrate nucleic acids by interacting with anionic nucleic acid cargo.\u00a0Compared with viral vectors, cationic nanocarriers also have other advantages, such as simplicity in large-scale production and less stringent vector size restrictions.\u00a0Although the benefits of nanocarriers in drug delivery have drawn widespread attention, toxicity has been a major obstacle in the application of cationic carriers. As nanocarriers of drug delivery systems (DDS) have been introduced into the human body, their toxicity has caused increasing public health concern. In research related to the preclinical or clinical use of cationic nanocarriers, researchers have discovered potential adverse effects due to cell and tissue interactions and the immunostimulation of nanocarriers.\u00a0Even the most widely used liposome complexes are limited due to the occurrence of toxicity such as inflammatory toxicity, liver toxicity, leukopenia, and thrombocytopenia.\u00a0It has been reported that cationic carriers such as liposomes and PEI accumulate in the lungs immediately after administration.\u00a0The lung’s inflammatory response is observed after several hours of topical application of the lipid plexus (atomization or intratracheal perfusion). Further research found that necrosis is one of the factors that cause this inflammatory response.\u00a0Necrosis is traditionally considered to be the accidental or passive type of cell death caused by non-physiological stress.\u00a0However, some recent evidence suggests that the execution of necrotic cell death can be regulated by a set of signal transduction pathways.\u00a0It is assumed that necrotic cells release endogenous molecules.\u00a0This hypothetical form of damage is called damage-associated molecular patterns (DAMPs).\u00a0Previous studies have found that mitochondria in the body can function as a major source of DAMP.\u00a0For example, mitochondrial DNA (mtDNA) has been reported to induce an inflammatory response after injury.\u00a0It is conceivable that the inflammatory response induced by cationic nanocarriers may be related to cell death and subsequent release of DAMPs, which in turn chemotactic and activate inflammatory cells.\u00a0To test this concept, the researchers conducted further exploration. It was found that injection of cationic nanocarriers (including cationic liposomes, PEI, and chitosan) could lead to the rapid appearance of necrotic cells.\u00a0Treatment with cationic nanocarriers inhibited Na + \/ K + -ATPase activity in vitro and in vivo, causing intracellular Na + overload with cell death.\u00a0The ability of cationic nanocarriers to induce cell necrosis depends on their positive surface charge.\u00a0Further analysis showed that cell necrosis induced by cationic nanocarriers and the resulting leakage of mitochondrial DNA can cause severe inflammation in the body, which is mediated by pathways involving TLR9 and MyD88 signaling.\u00a0therefore.\u00a0It can be determined that cationic nanocarriers induce acute cell necrosis through the interaction with Na + \/ K + -ATPase, and subsequent exposure of molecular patterns related to mitochondrial damage is a key event that mediates the inflammatory response.<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[],"class_list":["post-249","post","type-post","status-publish","format-standard","hentry","category-characteristic"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/posts\/249"}],"collection":[{"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/comments?post=249"}],"version-history":[{"count":3,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/posts\/249\/revisions"}],"predecessor-version":[{"id":508,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/posts\/249\/revisions\/508"}],"wp:attachment":[{"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/media?parent=249"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/categories?post=249"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/tags?post=249"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}