State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, 15 BeiSanhuan East Road, Beijing, 100029, China.
Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, 250117, Shangdong, China.
Small. 2018 Mar;14(9). doi: 10.1002/smll.201703152. Epub 2017 Dec 27.
The delivery of tumor-suppressive noncoding RNAs (ncRNAs) including short ncRNAs (i.e., miRNAs) and long ncRNAs (lncRNAs) is put forward to treat tumors. In this work, novel rodlike supramolecular nanoassemblies (CNC @CB[8] @ PGEA) of degradable poly(aspartic acid) (PAsp) derivatives-grafted cellulose nanocrystals (CNCs) and hydroxyl-rich polycations (ethanolamine-functionalized poly(glycidyl methacrylate), PGEA) are proposed via typical cucurbit[8]uril (CB[8])-based host-guest interactions for delivery of different ncRNAs to treat hepatocellular carcinoma (HCC). Spindly CNCs, one kind of natural polysaccharide nanoparticles, possess good biocompatibility and unique physico-chemical properties. PGEA with abundant hydroxyl groups is one promising gene carrier with low cytotoxicity. PAsp can benefit the disassembly and degradability of nanoassemblies within cells. CNC @ CB[8]@PGEA combines the different unique properties of CNC, PGEA, and PAsp. CNC @ CB[8] @ PGEA effectively complexes the expression constructs of miR-101 (plasmid pc3.0-miR-101) and lncRNA MEG3 (plasmid pc3.0-MEG3). CNC @ CB[8] @ PGEA produces much better transfection performances than PGEA-containing assembly units. In addition, the codelivery system of CNC @ CB[8] @ PGEA/(pc3.0-MEG3+pc3.0-miR-101) nanocomplexes demonstrates better efficacy in suppressing HCC than CNC @ CB[8] @ PGEA/pc3.0-MEG3 or CNC @ CB[8] @ PGEA/pc3.0-miR-101 nanocomplexes alone. Such rodlike supramolecular nanoassemblies will provide a promising means to produce efficient delivery vectors of versatile tumor-suppressive nucleic acids.
提出了递送肿瘤抑制性非编码 RNA（ncRNA），包括短 ncRNA（即 miRNA）和长 ncRNA（lncRNA），以治疗肿瘤。在这项工作中，通过典型的葫芦脲（CB[8]）-基于主体-客体相互作用，提出了可降解聚（天冬氨酸）（PAsp）衍生物接枝纤维素纳米晶体（CNCs）和富含羟基的聚阳离子（乙醇胺功能化聚（甲基丙烯酸缩水甘油酯），PGEA）的新型棒状超分子纳米组装体（CNC@CB[8]@PGEA），用于递送不同的 ncRNA 以治疗肝细胞癌（HCC）。细长的 CNC 是一种天然多糖纳米颗粒，具有良好的生物相容性和独特的物理化学性质。具有丰富羟基的 PGEA 是一种有前途的低细胞毒性基因载体。PAsp 有利于纳米组装体在细胞内的解组装和降解。CNC@CB[8]@PGEA 结合了 CNC、PGEA 和 PASP 的不同独特性质。CNC@CB[8]@PGEA 有效地将 miR-101 的表达构建体（质粒 pc3.0-miR-101）和 lncRNA MEG3（质粒 pc3.0-MEG3）进行了复合。与包含 PGEA 的组装单元相比，CNC@CB[8]@PGEA 产生了更好的转染性能。此外，CNC@CB[8]@PGEA/（pc3.0-MEG3+pc3.0-miR-101）纳米复合物的共递送系统在抑制 HCC 方面比 CNC@CB[8]@PGEA/pc3.0-MEG3 或 CNC@CB[8]@PGEA/pc3.0-miR-101 纳米复合物单独具有更好的疗效。这种棒状超分子纳米组装体将为生产有效的多功能肿瘤抑制性核酸递送载体提供一种有前途的方法。
