Metallic Cation-Mediated Entrapment of Nucleic Acids on Mesoporous Silica Surface: Application in Castration-Resistant Prostate Cancer
Metallic Cation-Mediated Entrapment of Nucleic Acids on Mesoporous Silica Surface: Application in Castration-Resistant Prostate Cancer
复制标题
DOI：
10.1021/acs.chemmater.3c01174
复制
发表时间：
2023-12
影响因子：
8.6
通讯作者：
Angelea Maestas-Olguin;Marian Olewine;Sheymah Thabata;Johanna Tsala Ebode;Mariella Arcos;Jacob A Krawchuck;Eric N. Coker;A. Brearley;Xiang Xue;J. Watt;Achraf Noureddine;C. Brinker
中科院分区：
文献类型：
--
作者：
Angelea Maestas-Olguin;Marian Olewine;Sheymah Thabata;Johanna Tsala Ebode;Mariella Arcos;Jacob A Krawchuck;Eric N. Coker;A. Brearley;Xiang Xue;J. Watt;Achraf Noureddine;C. Brinker
使用外源核酸技术来调节由基因突变引起的异常蛋白质表达是用于治疗诸如晚期前列腺癌（PC）的疾病的有前景的治疗方法。基于核酸的治疗剂的前景取决于有效保护核酸免受核酸酶降解并将核酸递送至靶细胞的胞质溶胶的平台的开发。在这项工作中，我们提出了一个二价金属介导的核酸截留策略与多孔二氧化硅基质的发展。这种简单的策略导致siRNA（>60%）和mRNA（>80%）的有效负载百分比以及它们在相关生物环境中的释放（80%）。此外，我们的数据支持当前方法减少内体截留并支持介孔二氧化硅纳米颗粒（LC-MSN）的脂质包覆。金属增强的纳米系统的生物相容性，稳定性，并在PC的体外，卵外和体内模型内的循环进行评估。
The use of exogenous nucleic acid technologies to modulate aberrant protein expression resulting from genetic mutations is a promising therapeutic approach for the treatment of diseases such as advanced prostate cancer (PC). The promise of nucleic-based therapeutics is dependent on the development of platforms that effectively protect nucleic acids from nuclease degradation and deliver the nucleic acids to the cytosol of target cells. In this work, we present the development of a divalent metal-mediated nucleic acid entrapment strategy with a porous silica matrix. This simple strategy results in efficient loading percentages of both siRNA (>60%) and mRNA (>80%) as well as their release within relevant biological environments (80%). Additionally, our data supports that the current method reduces endosomal entrapment and supports the lipid coating of mesoporous silica nanoparticles (LC-MSNs). The metal-enhanced nanosystem is assessed for biocompatibility, stability, and circulation within in vitro, ex ovo, and in vivo models of PC.