Malik Shipra, Kumar Vikas, Liu Chung-Hao, Shih Kuo-Chih, Krueger Susan, Nieh Mu-Ping, Bahal Raman
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA.
Polymer Program, Institute of Material Sciences, University of Connecticut, 191 Auditorium Road, Storrs, CT, 06269, USA.
Adv Funct Mater. 2022 Feb 9;32(7). doi: 10.1002/adfm.202109552. Epub 2021 Nov 5.
Peptide nucleic acids (PNAs) are nucleic acid analogs with superior hybridization properties and enzymatic stability than deoxyribonucleic acid (DNA). In addition to gene targeting applications, PNAs have garnered significant attention as bio-polymer due to the Watson-Crick -based molecular recognition and flexibility of synthesis. Here, we engineered PNA amphiphiles using chemically modified gamma PNA (8 mer in length) containing hydrophilic diethylene glycol units at the gamma position and covalently conjugated lauric acid (C12) as a hydrophobic moiety. Gamma PNA (γPNA) amphiphiles self-assemble into spherical vesicles. Further, we formulate nano-assemblies using the amphiphilic γPNA as a polymer via ethanol injection-based protocols. We perform comprehensive head-on comparison of the physicochemical and cellular uptake properties of PNA derived self- and nano-assemblies. Small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) analysis reveal ellipsoidal morphology of γPNA nano-assemblies that results in superior cellular delivery compate to the spherical self-assembly. Next, we compare the functional activities of γPNA self-and nano-assemblies in lymphoma cells via multiple endpoints, including gene expression, cell viability, and apoptosis-based assays. Overall, we establish that γPNA amphiphile is a functionally active bio-polymer to formulate nano-assemblies for a wide range of biomedical applications.
肽核酸（PNA）是一种核酸类似物，与脱氧核糖核酸（DNA）相比，具有更优异的杂交特性和酶稳定性。除了基因靶向应用外，由于基于沃森-克里克的分子识别和合成灵活性，PNA作为生物聚合物也受到了广泛关注。在此，我们设计了PNA两亲物，使用在γ位置含有亲水性二甘醇单元的化学修饰γPNA（长度为8聚体），并共价连接月桂酸（C12）作为疏水部分。γPNA两亲物自组装成球形囊泡。此外，我们通过基于乙醇注射的方案，使用两亲性γPNA作为聚合物来制备纳米组装体。我们对PNA衍生的自组装体和纳米组装体的物理化学性质和细胞摄取特性进行了全面的直接比较。小角中子散射（SANS）和小角X射线散射（SAXS）分析揭示了γPNA纳米组装体的椭圆形形态，这导致其细胞递送能力优于球形自组装体。接下来，我们通过多个终点，包括基因表达、细胞活力和基于凋亡的检测，比较了γPNA自组装体和纳米组装体在淋巴瘤细胞中的功能活性。总体而言，我们确定γPNA两亲物是一种功能活性生物聚合物，可用于制备用于广泛生物医学应用的纳米组装体。
