McKetta Department of Chemical Engineering, 200 E. Dean Keeton St. Stop C0400, Austin, TX 78712, USA; Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, 107 W Dean Keeton Street Stop C0800, Austin, TX 78712, USA.
McKetta Department of Chemical Engineering, 200 E. Dean Keeton St. Stop C0400, Austin, TX 78712, USA.
J Control Release. 2021 Apr 10;332:608-619. doi: 10.1016/j.jconrel.2021.03.004. Epub 2021 Mar 3.
Advances in the formulation of nucleic acid-based therapeutics have rendered them a promising avenue for treating diverse ailments. Nonetheless, clinical translation of these therapies is hindered by a lack of strategies to ensure the delivery of these nucleic acids in a safe, efficacious manner with the required spatial and temporal control. To this aim, environmentally responsive hydrogels are of interest due to their ability to provide the desired characteristics of a protective carrier for siRNA delivery. Previous work in our laboratory has demonstrated the ability to synthesize nanoparticle formulations with targeted pK, swelling, and surface PEG density. Here, a library of nanoparticle formulations was assessed on their in vitro toxicity, hemolytic capacity, siRNA loading, and gene-silencing efficacy. Successful candidates exhibited the lowest degrees of cytotoxicity, pH-dependent membrane disruption potential, the highest siRNA loading, and the highest transfection efficacies.
核酸治疗药物的不断发展，为治疗各种疾病提供了一条很有前途的途径。然而，这些疗法的临床转化受到缺乏策略的阻碍，无法以安全、有效的方式，在所需的空间和时间内控制这些核酸的传递。为此，环境响应水凝胶因其能够为 siRNA 传递提供所需的保护载体特性而受到关注。我们实验室之前的工作已经证明了能够合成具有靶向 pK、溶胀和表面 PEG 密度的纳米颗粒制剂的能力。在这里，对一组纳米颗粒制剂进行了体外毒性、溶血能力、siRNA 负载和基因沉默效果的评估。成功的候选物表现出最低的细胞毒性、pH 依赖性膜破坏潜力、最高的 siRNA 负载和最高的转染效率。
