Pasquale Cepparulo, Ornella Cuomo, Virginia Campani, Antonio Vinciguerra, Maria Josè Sisalli, Valeria Nele, Serenella Anzilotti, Valeria Valsecchi, Antonella Casamassa, Paola Brancaccio, Antonella Scorziello, Giuseppe De Rosa, Lucio Annunziato, Giuseppe Pignataro
{"title":"包裹在三铁蛋白结合脂质纳米颗粒中的抗miRNA103/107可穿过血脑屏障,减轻脑缺血损伤。","authors":"Pasquale Cepparulo, Ornella Cuomo, Virginia Campani, Antonio Vinciguerra, Maria Josè Sisalli, Valeria Nele, Serenella Anzilotti, Valeria Valsecchi, Antonella Casamassa, Paola Brancaccio, Antonella Scorziello, Giuseppe De Rosa, Lucio Annunziato, Giuseppe Pignataro","doi":"10.1016/j.omtn.2024.102131","DOIUrl":null,"url":null,"abstract":"<p>MicroRNA(miRNA), by post-transcriptionally regulating the expression of genes involved in stroke response, represent important effectors in stroke pathophysiology. Recently, the 103/107 miRNA family emerged as possible therapeutic target in stroke, as it controls the expression of sodium calcium exchanger 1, a plasmamembrane transporter that plays a fundamental role in stroke pathophysiology. Although the neuroprotective properties of this and other miRNAs are promising, several pharmacokinetic drawbacks remain to be faced for the development of a translatable therapy based on small RNAs in CNS diseases. In the present study, to overcome these limitations, the anti-miRNA103/107 was encapsulated in specific preparations of lipid nanoparticles(LNPs), and their effectiveness was evaluated both in an <em>in vitro</em> model of hypoxia represented by primary neuronal cortical cultures exposed to Oxygen and Glucose Deprivation followed by reoxygenation, and in an <em>in vivo</em> model of stroke obtained in rats exposed to transient occlusion of the Middle Cerebral Artery. The results of the present study demonstrated that the encapsulation of anti-miRNA103/107 in transferrin-conjugated PEG-stabilized lipid nanoparticles allowed the blood-brain barrier crossing and significantly reduce brain ischemic damage. The present achievements pave the way for the exploitation of a systemic intravenous miRNA delivery strategy in stroke therapy.</p>","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":null,"pages":null},"PeriodicalIF":6.5000,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anti-miRNA103/107 encapsulated in trasnferrin-conjugated lipid nanoparticles crosses the blood-brain barrier and reduces brain ischemic damage.\",\"authors\":\"Pasquale Cepparulo, Ornella Cuomo, Virginia Campani, Antonio Vinciguerra, Maria Josè Sisalli, Valeria Nele, Serenella Anzilotti, Valeria Valsecchi, Antonella Casamassa, Paola Brancaccio, Antonella Scorziello, Giuseppe De Rosa, Lucio Annunziato, Giuseppe Pignataro\",\"doi\":\"10.1016/j.omtn.2024.102131\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>MicroRNA(miRNA), by post-transcriptionally regulating the expression of genes involved in stroke response, represent important effectors in stroke pathophysiology. Recently, the 103/107 miRNA family emerged as possible therapeutic target in stroke, as it controls the expression of sodium calcium exchanger 1, a plasmamembrane transporter that plays a fundamental role in stroke pathophysiology. Although the neuroprotective properties of this and other miRNAs are promising, several pharmacokinetic drawbacks remain to be faced for the development of a translatable therapy based on small RNAs in CNS diseases. In the present study, to overcome these limitations, the anti-miRNA103/107 was encapsulated in specific preparations of lipid nanoparticles(LNPs), and their effectiveness was evaluated both in an <em>in vitro</em> model of hypoxia represented by primary neuronal cortical cultures exposed to Oxygen and Glucose Deprivation followed by reoxygenation, and in an <em>in vivo</em> model of stroke obtained in rats exposed to transient occlusion of the Middle Cerebral Artery. The results of the present study demonstrated that the encapsulation of anti-miRNA103/107 in transferrin-conjugated PEG-stabilized lipid nanoparticles allowed the blood-brain barrier crossing and significantly reduce brain ischemic damage. The present achievements pave the way for the exploitation of a systemic intravenous miRNA delivery strategy in stroke therapy.</p>\",\"PeriodicalId\":18821,\"journal\":{\"name\":\"Molecular Therapy. Nucleic Acids\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.5000,\"publicationDate\":\"2024-02-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Therapy. Nucleic Acids\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.omtn.2024.102131\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy. Nucleic Acids","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.omtn.2024.102131","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Anti-miRNA103/107 encapsulated in trasnferrin-conjugated lipid nanoparticles crosses the blood-brain barrier and reduces brain ischemic damage.
MicroRNA(miRNA), by post-transcriptionally regulating the expression of genes involved in stroke response, represent important effectors in stroke pathophysiology. Recently, the 103/107 miRNA family emerged as possible therapeutic target in stroke, as it controls the expression of sodium calcium exchanger 1, a plasmamembrane transporter that plays a fundamental role in stroke pathophysiology. Although the neuroprotective properties of this and other miRNAs are promising, several pharmacokinetic drawbacks remain to be faced for the development of a translatable therapy based on small RNAs in CNS diseases. In the present study, to overcome these limitations, the anti-miRNA103/107 was encapsulated in specific preparations of lipid nanoparticles(LNPs), and their effectiveness was evaluated both in an in vitro model of hypoxia represented by primary neuronal cortical cultures exposed to Oxygen and Glucose Deprivation followed by reoxygenation, and in an in vivo model of stroke obtained in rats exposed to transient occlusion of the Middle Cerebral Artery. The results of the present study demonstrated that the encapsulation of anti-miRNA103/107 in transferrin-conjugated PEG-stabilized lipid nanoparticles allowed the blood-brain barrier crossing and significantly reduce brain ischemic damage. The present achievements pave the way for the exploitation of a systemic intravenous miRNA delivery strategy in stroke therapy.
期刊介绍:
Molecular Therapy Nucleic Acids is an international, open-access journal that publishes high-quality research in nucleic-acid-based therapeutics to treat and correct genetic and acquired diseases. It is the official journal of the American Society of Gene & Cell Therapy and is built upon the success of Molecular Therapy. The journal focuses on gene- and oligonucleotide-based therapies and publishes peer-reviewed research, reviews, and commentaries. Its impact factor for 2022 is 8.8. The subject areas covered include the development of therapeutics based on nucleic acids and their derivatives, vector development for RNA-based therapeutics delivery, utilization of gene-modifying agents like Zn finger nucleases and triplex-forming oligonucleotides, pre-clinical target validation, safety and efficacy studies, and clinical trials.