Multifunctional Glyco-Nanofibers: siRNA Induced Supermolecular Assembly for Codelivery In Vivo
Multifunctional Glyco-Nanofibers: siRNA Induced Supermolecular Assembly for Codelivery In Vivo
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多功能糖纳米纤维：siRNA 诱导超分子组装用于体内代码传递
DOI：
10.1002/adfm.201703083
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发表时间：
2017-11-24
影响因子：
19
通讯作者：
Pei, Zhichao
中科院分区：
文献类型：
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作者：
Chang, Yincheng;Lv, Yinghua;Pei, Zhichao
在安全有效的载体中靶向共递送和控制释放药物/siRNA（小干扰RNA）对于克服耐药性和在癌症治疗中的最佳功效具有很大的希望;然而，合理设计和制备此类载体仍然是一个关键挑战。因此，通过聚阴离子siRNA和阳离子囊泡的超分子组装来制造糖纳米纤维（GNF），以在体外和体内同时递送siRNA和盐酸阿霉素（DOX）。囊泡是通过带正电荷的两亲性乳糖衍生物的自组装产生的，该乳糖衍生物在分子的两端具有乳糖部分和二茂铁单元。GNF显示出优异的生物相容性、增强的细胞穿透能力和肝癌靶向性。在体外实验中观察到负载DOX的GNF具有高的siRNA转运效率、有效的基因沉默能力以及增强的对HepG 2细胞的细胞毒性。此外，体内实验显示DOX对HepG 2和HepG 2/ADR皮下荷瘤裸鼠的全身毒性降低和治疗功效增强。本工作证明了阳离子碳水化合物和聚阴离子siRNA之间的静电自组装是一种方便有效的策略，以制备安全有效的药物/siRNA共递送的单一载体，其可用于联合联合收割机化疗和基因治疗癌症和其他疾病。
Targeted codelivery and controlled release of drug/siRNA (small interfering RNA) in a safe and effective vehicle hold great promises for overcoming drug resistance and optimal efficacy in cancer treatment; however, rational design and preparation of such vehicles remain a critical challenge. Thus, glyco-nanofibers (GNFs) are fabricated via supermolecular assembly of polyanionic siRNA and cationic vesicles to simultaneously deliver siRNA and doxorubicin hydrochloride (DOX) in vitro and in vivo. The vesicles are created through self-assembly of a positively charged amphiphilic lactose derivative featuring a lactose moiety and a ferrocenium unit on either end of the molecule. The GNFs display excellent biocompatibility, enhanced cell-penetrating ability, and hepatoma targetability. The high transport efficiency of siRNA, effective gene silencing ability, and enhanced cytotoxicity to HepG2 cells of GNFs loaded with DOX are observed in vitro. Furthermore, in vivo experiments show reduced systemic toxicity and enhanced therapeutic efficacy of DOX to both HepG2 and HepG2/ADR subcutaneous tumor-bearing nude mice. This work proves the electrostatic self-assembly between cationic carbohydrates and polyanionic siRNA to be a convenient and effective strategy to fabricate a single vehicle for safe and effective codelivery of drug/siRNA, which can be used to combine chemo- and gene-therapy against cancers and other diseases.