title: Multifunctional nanocarrier based on clay nanotubes for efficient intracellular siRNA delivery and gene silencing.
abstract: RNA interference-mediated gene silencing relating to disease has recently emerged as a powerful method in gene therapy. Despite the promises, effective transport of siRNA with minimal side effects remains a challenge. Halloysites are cheap and naturally available aluminosilicate clay nanotubes with high mechanical strength and biocompatibility. In this study, a novel multifunctional nanocarrier based on functionalized halloysite nanotubes (f-HNTs) has been developed via electrostatic layer-by-layer assembling approach for loading and intracellular delivery of therapeutic antisurvivin siRNA and simultaneously tracking their intracellular transport, in which PEI-modified HNTs are used as gene vector, antisurvivin siRNA as gene therapeutic agent, and mercaptoacetic acid-capped CdSe quantum dots as fluorescent labeling probes. The successful assembly of the f-HNTs-siRNA complexes was systematically characterized by transmission electron microscopy (TEM), UV-visible spectrophotometry, Zeta potential measurement, fluorescence spectrophotometry, and electrochemical impedance spectroscopy. Confocal microscopy, biological TEM, and flow cytometry studies revealed that the complexes enabled the efficient intracellular delivery of siRNA for cell-specific gene silencing. MTT assays exhibited that the complexes can enhance antitumor activity. Furthermore, Western blot analysis showed that f-HNTs-mediated siRNA delivery effectively knocked down gene expression of survivin and thereby decreased the levels of target proteins of PANC-1 cells. Therefore, this study suggested that the synthesized f-HNTs were a new effective drug delivery system for potential application in cancer gene therapy.
authors.affiliation: The Education Ministry Key Laboratory of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Department of Chemistry, College of Life and Environmental Sciences, Shanghai Normal University, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Shi
authors.forename: Chusen
authors.initials: C
authors.lastname: Huang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiahui
authors.initials: J
authors.lastname: Wu
authors.forename: Hebai
authors.initials: H
authors.lastname: Shen
authors.forename: Nengqin
authors.initials: N
authors.lastname: Jia
mesh_terms: D000538:Aluminum Silicates / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry; D001693:Biological Transport, Active; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077215:Clay; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D015316:Genetic Therapy; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008422:Materials Testing; D046529:Microscopy, Electron, Transmission; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D045663:Quantum Dots; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D013499:Surface Properties; D000077022:Survivin
chemical_list: D000538:Aluminum Silicates; C107489:BIRC5 protein, human; D001672:Biocompatible Materials; D004337:Drug Carriers; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D000077215:Clay
keywords: Multifunctional nanocarrier; gene silencing; halloysite nanotubes; intracellular delivery; siRNA