{"title":"Metal Ion-Condensed DNA Nanoparticle Library: Phase Separation and Transition and Antisense Therapy Applications","authors":"Jeesu Moon, Sang-Won Kim, Jae-Seung Lee","doi":"10.1021/acsami.4c16869","DOIUrl":null,"url":null,"abstract":"DNA condensation has long been investigated as a fundamental cellular activity and is known to be driven by the mediation of diverse condensing agents. The phase behaviors of DNA during condensation are particularly interesting because the complicated molecular structure of natural nucleotides fundamentally allows electrostatic, coordinate covalent, and various other secondary interactions with the condensing agents. Recently, metal ion (M<sup>n+</sup>)-induced DNA condensation has emerged as a powerful approach to synthesizing nanoparticulate DNA structures suitable for therapeutic gene delivery. However, how the DNA phase changes during M<sup>n+</sup>-induced DNA condensation has rarely been observed and is not understood yet. In this study, a library of M<sup>n+</sup>-condensed DNA nanoparticles (M<sup>n+</sup>-CDNPs) was established using 30 different types of M<sup>n+</sup>s, and their phase behaviors during condensation were elucidated using spherical nucleic acids (SNAs) as electron microscopic labels. Importantly, the phase transition and separation of DNA were demonstrated to be driven by the M<sup>n+</sup>s into either the growth of individual DNA particles or the fission of bulky DNA aggregates. Pt<sup>2+</sup> and Eu<sup>3+</sup> were chosen as model systems for the demonstration. The hard and soft acid nature of M<sup>n+</sup> is presumably the underlying driving force of these phase transitions. In addition, the M<sup>n+</sup>-controlled anticancer therapeutic efficiency of the M<sup>n+</sup>-CDNP library as a state-of-the-art gene delivery platform was demonstrated even for unmodified antisense oligonucleotides in association with the potential toxicity of the M<sup>n+</sup>s released from the M<sup>n+</sup>-CDNPs. This comprehensive study of the M<sup>n+</sup>-dependent condensation of nucleic acids provides profound insights into the chemistry of the nucleic acid–M<sup>n+</sup> interactions and the reliable theragnostic applications of M<sup>n+</sup>-CDNPs as functional nucleic acid nanostructures.","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":null,"pages":null},"PeriodicalIF":8.3000,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Materials & Interfaces","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1021/acsami.4c16869","RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
DNA condensation has long been investigated as a fundamental cellular activity and is known to be driven by the mediation of diverse condensing agents. The phase behaviors of DNA during condensation are particularly interesting because the complicated molecular structure of natural nucleotides fundamentally allows electrostatic, coordinate covalent, and various other secondary interactions with the condensing agents. Recently, metal ion (Mn+)-induced DNA condensation has emerged as a powerful approach to synthesizing nanoparticulate DNA structures suitable for therapeutic gene delivery. However, how the DNA phase changes during Mn+-induced DNA condensation has rarely been observed and is not understood yet. In this study, a library of Mn+-condensed DNA nanoparticles (Mn+-CDNPs) was established using 30 different types of Mn+s, and their phase behaviors during condensation were elucidated using spherical nucleic acids (SNAs) as electron microscopic labels. Importantly, the phase transition and separation of DNA were demonstrated to be driven by the Mn+s into either the growth of individual DNA particles or the fission of bulky DNA aggregates. Pt2+ and Eu3+ were chosen as model systems for the demonstration. The hard and soft acid nature of Mn+ is presumably the underlying driving force of these phase transitions. In addition, the Mn+-controlled anticancer therapeutic efficiency of the Mn+-CDNP library as a state-of-the-art gene delivery platform was demonstrated even for unmodified antisense oligonucleotides in association with the potential toxicity of the Mn+s released from the Mn+-CDNPs. This comprehensive study of the Mn+-dependent condensation of nucleic acids provides profound insights into the chemistry of the nucleic acid–Mn+ interactions and the reliable theragnostic applications of Mn+-CDNPs as functional nucleic acid nanostructures.
期刊介绍:
ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.