{"title":"肝特异性电离脂质纳米载体在siRNA递送中的评价","authors":"Shilpa Rana , Archana Bhatnagar , Suman Singh , Nirmal Prabhakar","doi":"10.1016/j.chemphyslip.2022.105207","DOIUrl":null,"url":null,"abstract":"<div><p><span><span>Hepcidin, a key regulator of </span>iron homeostasis, has been implicated in the pathogenesis of various iron-related diseases. Although </span>small interfering RNA<span><span><span> (siRNA) are potent to modulate the expression of hepcidin, their bioavailability remains a major issue. The β-galactopyranoside-conjugated liposomes (GAL-liposome) targeting liver synthesized hepcidin were prepared by thin lipid film<span><span> hydration method to encapsulate siRNA and the conjugation of β-galactopyranoside to the lipid </span>nanocarrier was achieved by covalent </span></span>chemistry<span>. The prepared siRNA loaded GAL-lip were spherical with around 50 nm radius in size as observed by HR-TEM. The zeta potential<span> and polydispersity index<span> of the prepared liposomes were − 19.9 ± 0.96 mV and 0.44 ± 0.05, respectively. The encapsulation efficiency as determined by dialysis bag method was around 91.76 ± 1.74%. The cell viability<span> and cellular uptake analysis was examined in HepG2 cells by MTT assay and flow </span></span></span></span></span>cytometry<span><span>, respectively. The stability and cumulative release of siRNA was also assessed. The hepcidin mRNA expression on administration of siRNA loaded GAL-lip was determined in HepG2 cells and in lipopolysaccharide-induced mice model followed by examining itsin vivo biodistribution by </span>fluorescence microscopy<span>. The results suggested thatsiRNA loaded GAL-lip reduced the hepcidin levels, thus, highlighting a novel ligand conjugated ionizable lipid-based nanocarrier for inducing RNA interference.</span></span></span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"246 ","pages":"Article 105207"},"PeriodicalIF":3.4000,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Evaluation of liver specific ionizable lipid nanocarrier in the delivery of siRNA\",\"authors\":\"Shilpa Rana , Archana Bhatnagar , Suman Singh , Nirmal Prabhakar\",\"doi\":\"10.1016/j.chemphyslip.2022.105207\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span><span>Hepcidin, a key regulator of </span>iron homeostasis, has been implicated in the pathogenesis of various iron-related diseases. Although </span>small interfering RNA<span><span><span> (siRNA) are potent to modulate the expression of hepcidin, their bioavailability remains a major issue. The β-galactopyranoside-conjugated liposomes (GAL-liposome) targeting liver synthesized hepcidin were prepared by thin lipid film<span><span> hydration method to encapsulate siRNA and the conjugation of β-galactopyranoside to the lipid </span>nanocarrier was achieved by covalent </span></span>chemistry<span>. The prepared siRNA loaded GAL-lip were spherical with around 50 nm radius in size as observed by HR-TEM. The zeta potential<span> and polydispersity index<span> of the prepared liposomes were − 19.9 ± 0.96 mV and 0.44 ± 0.05, respectively. The encapsulation efficiency as determined by dialysis bag method was around 91.76 ± 1.74%. The cell viability<span> and cellular uptake analysis was examined in HepG2 cells by MTT assay and flow </span></span></span></span></span>cytometry<span><span>, respectively. The stability and cumulative release of siRNA was also assessed. The hepcidin mRNA expression on administration of siRNA loaded GAL-lip was determined in HepG2 cells and in lipopolysaccharide-induced mice model followed by examining itsin vivo biodistribution by </span>fluorescence microscopy<span>. The results suggested thatsiRNA loaded GAL-lip reduced the hepcidin levels, thus, highlighting a novel ligand conjugated ionizable lipid-based nanocarrier for inducing RNA interference.</span></span></span></p></div>\",\"PeriodicalId\":275,\"journal\":{\"name\":\"Chemistry and Physics of Lipids\",\"volume\":\"246 \",\"pages\":\"Article 105207\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2022-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemistry and Physics of Lipids\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0009308422000354\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemistry and Physics of Lipids","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0009308422000354","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Evaluation of liver specific ionizable lipid nanocarrier in the delivery of siRNA
Hepcidin, a key regulator of iron homeostasis, has been implicated in the pathogenesis of various iron-related diseases. Although small interfering RNA (siRNA) are potent to modulate the expression of hepcidin, their bioavailability remains a major issue. The β-galactopyranoside-conjugated liposomes (GAL-liposome) targeting liver synthesized hepcidin were prepared by thin lipid film hydration method to encapsulate siRNA and the conjugation of β-galactopyranoside to the lipid nanocarrier was achieved by covalent chemistry. The prepared siRNA loaded GAL-lip were spherical with around 50 nm radius in size as observed by HR-TEM. The zeta potential and polydispersity index of the prepared liposomes were − 19.9 ± 0.96 mV and 0.44 ± 0.05, respectively. The encapsulation efficiency as determined by dialysis bag method was around 91.76 ± 1.74%. The cell viability and cellular uptake analysis was examined in HepG2 cells by MTT assay and flow cytometry, respectively. The stability and cumulative release of siRNA was also assessed. The hepcidin mRNA expression on administration of siRNA loaded GAL-lip was determined in HepG2 cells and in lipopolysaccharide-induced mice model followed by examining itsin vivo biodistribution by fluorescence microscopy. The results suggested thatsiRNA loaded GAL-lip reduced the hepcidin levels, thus, highlighting a novel ligand conjugated ionizable lipid-based nanocarrier for inducing RNA interference.
期刊介绍:
Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications.
Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.