3 years ago

Multifunctional Glyco-Nanofibers: siRNA Induced Supermolecular Assembly for Codelivery In Vivo

Multifunctional Glyco-Nanofibers: siRNA Induced Supermolecular Assembly for Codelivery In Vivo
Peng Wei, Wenxian Zeng, Xueliang Li, Liang Pu, Yincheng Chang, Zhichao Pei, Yuxin Pei, Kui Yang, Yinghua Lv, Xiaoxu Chen, Chenxi Hou, Pengfei Zhang, Yuchao Lu
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. Glyco-nanofibers (GNFs) are synthesized via supermolecular assembly of polyanionic small interfering RNA (siRNA) and cationic vesicles assembled by an amphiphilic lactose derivative capped with cationic ferrocenium. The obtained GNFs display excellent biocompatibility, enhanced cell-penetrating ability, and hepatoma targetability, enabling highly efficient codelivery of drug/siRNA to reduce adverse side effects and overcome multidrug resistance of cancer in vitro and in vivo.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/adfm.201703083

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