RNA-based micelles: A novel platform for paclitaxel loading and delivery.
RNA-based micelles: A novel platform for paclitaxel loading and delivery.
复制标题
DOI：
10.1016/j.jconrel.2018.02.014
复制
发表时间：
2018-04-28
期刊：
影响因子：
--
通讯作者：
Guo P
中科院分区：
文献类型：
--
作者：
Shu Y;Yin H;Rajabi M;Li H;Vieweger M;Guo S;Shu D;Guo P
RNA可以作为生物技术和生物医学应用中自下而上制造纳米结构的强大构建模块。除了目前利用碱基配对、基序堆积和三级相互作用的自组装策略之外，我们首次报道了基于RNA的胶束纳米构建体的形成，其中胆固醇分子缀合到分支pRNA三向连接（3 WJ）基序的一个螺旋末端上。所得到的两亲性RNA胶束由亲水性RNA头部和共价连接的疏水性脂质尾部组成，其可以通过疏水相互作用在水溶液中自发地组装。利用pRNA 3 WJ分支结构，组装的RNA胶束能够护送多个功能模块。作为用于递送治疗剂的概念证明，将Paclitaxel装载到具有显著改善的水溶性的RNA胶束中。通过琼脂糖凝胶电泳、原子力显微镜（AFM）、动态光散射（DLS）和荧光尼罗红包封试验证实了载药RNA胶束的成功构建。估计的临界胶束形成浓度范围为39 nM至78 nM。装载紫杉醇的RNA胶束可以内化到癌细胞中并抑制其增殖。进一步的研究表明，紫杉醇负载的RNA胶束以Caspase-3依赖的方式诱导癌细胞凋亡，但单独的RNA胶束表现出低细胞毒性。最后，紫杉醇负载的RNA胶束在体内靶向肿瘤，而不在健康组织和器官中积累。也没有或非常低的促炎反应诱导。因此，多价性、癌细胞渗透性、与可控组装组合、低或无毒性质以及肿瘤靶向都是有希望的特征，使得我们的pRNA胶束成为潜在药物递送的合适平台。
RNA can serve as powerful building blocks for bottom-up fabrication of nanostructures for biotechnological and biomedical applications. In addition to current self -assembly strategies utilizing base pairing, motif piling and tertiary interactions, we reported for the first time the formation of RNA based micellar nanoconstruct with a cholesterol molecule conjugated onto one helical end of a branched pRNA three-way junction (3WJ) motif. The resulting amphiphilic RNA micelles consist of a hydrophilic RNA head and a covalently linked hydrophobic lipid tail that can spontaneously assemble in aqueous solution via hydrophobic interaction. Taking advantage of pRNA 3WJ branched structure, the assembled RNA micelles are capable of escorting multiple functional modules. As a proof of concept for delivery for therapeutics, Paclitaxel was loaded into the RNA micelles with significantly improved water solubility. The successful construction of the drug loaded RNA micelles was confirmed and characterized by agarose gel electrophoresis, atomic force microscopy (AFM), dynamic light scattering (DLS), and fluorescence Nile Red encapsulation assay. The estimate critical micelle formation concentration ranges from 39nM to 78nM. The Paclitaxel loaded RNA micelles can internalize into cancer cells and inhibit their proliferation. Further studies showed that the Paclitaxel loaded RNA micelles induced cancer cell apoptosis in a Caspase-3 dependent manner but RNA micelles alone exhibited low cytotoxicity. Finally, the Paclitaxel loaded RNA micelles targeted to tumor in vivo without accumulation in healthy tissues and organs. There is also no or very low induction of pro-inflammatory response. Therefore, multivalence, cancer cell permeability, combined with controllable assembly, low or non toxic nature, and tumor targeting are all promising features that make our pRNA micelles a suitable platform for potential drug delivery.
登录
查看更多内容
DOI：
10.1016/j.omtn.2017.10.010
发表时间：
2017-12-15
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Guo S;Li H;Ma M;Fu J;Dong Y;Guo P
通讯作者：
Guo P
用于自动纳米医学的siRNA官能化RNA纳米颗粒的设计和自组装。
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
5.8
作者：
Deng, Jiexin;Huang, Leaf;Liu, Feng
通讯作者：
Liu, Feng
影响因子：
3.9
作者：
Dentinger, PM;Simmons, BA;Sprague, M
通讯作者：
Sprague, M
影响因子：
2.9
作者：
Binzel, Daniel W.;Khisamutdinov, Emil F.;Guo, Peixuan
通讯作者：
Guo, Peixuan