Biocompatible, chimeric peptide-condensed supramolecular nanoparticles for tumor cell-specific siRNA delivery and gene silencing

RNA interference (RNAi) was first literaturally reported in 1998 and has become rapidly a promising tool for therapeutic applications in gene therapy. In a typical RNAi process, small interfering RNAs (siRNA) are used to specifically downregulate the expression of the targeted gene, known as the term “gene silencing.” One key point for successful gene silencing is to employ a safe and efficient siRNA delivery system. In this context, dendrimers are emerging as potential nonviral vectors to deliver siRNA for RNAi purpose. Dendrimers have attracted intense interest since their emanating research in the 1980s and are extensively studied as efficient DNA delivery vectors in gene transfer applications, due to their unique features based on the well-defined and multivalent structures. Knowing that DNA and RNA possess a similar structure in terms of nucleic acid framework and the electronegative nature, one can also use the excellent DNA delivery properties of dendrimers to develop effective siRNA delivery systems. In this review, the development of dendrimer-based siRNA delivery vectors is summarized, focusing on the vector features (siRNA delivery efficiency, cytotoxicity, etc.) of different types of dendrimers and the related investigations on structure-activity relationship to promote safe and efficient siRNA delivery system.

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A surface-mediated siRNA delivery system developed with chitosan/hyaluronic acid-siRNA multilayer films through layer-by-layer self-assembly

Applied Surface Science ◽

10.1016/j.apsusc.2016.06.051 ◽

2016 ◽

Vol 389 ◽

pp. 395-403 ◽

Cited By ~ 2

Author(s):

Lijuan Wu ◽

Changlin Wu ◽

Guangwan Liu ◽

Nannan Liao ◽

Fang Zhao ◽

...

Keyword(s):

Hyaluronic Acid ◽

Delivery System ◽

Self Assembly ◽

Sirna Delivery ◽

Multilayer Films ◽

Layer By Layer ◽

Sirna Delivery System

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Gene Silencing via RNAi and siRNA Quantification in Tumor Tissue Using MEND, a Liposomal siRNA Delivery System

Molecular Therapy ◽

10.1038/mt.2013.57 ◽

2013 ◽

Vol 21 (6) ◽

pp. 1195-1203 ◽

Cited By ~ 92

Author(s):

Yu Sakurai ◽

Hiroto Hatakeyama ◽

Yusuke Sato ◽

Mamoru Hyodo ◽

Hidetaka Akita ◽

...

Keyword(s):

Gene Silencing ◽

Delivery System ◽

Tumor Tissue ◽

Sirna Delivery ◽

Sirna Delivery System

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A Dual Targeting Dendrimer-Mediated siRNA Delivery System for Effective Gene Silencing in Cancer Therapy

Journal of the American Chemical Society ◽

10.1021/jacs.8b10021 ◽

2018 ◽

Vol 140 (47) ◽

pp. 16264-16274 ◽

Cited By ~ 57

Author(s):

Yiwen Dong ◽

Tianzhu Yu ◽

Ling Ding ◽

Erik Laurini ◽

Yuanyu Huang ◽

...

Keyword(s):

Cancer Therapy ◽

Gene Silencing ◽

Delivery System ◽

Sirna Delivery ◽

Dual Targeting ◽

Sirna Delivery System

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Construction of negatively charged and environment-sensitive nanomedicine for tumor-targeted efficient siRNA delivery

Chemical Communications ◽

10.1039/c5cc09181k ◽

2016 ◽

Vol 52 (6) ◽

pp. 1194-1197 ◽

Cited By ~ 18

Author(s):

Yong Wang ◽

Hong Xiao ◽

Jing Fang ◽

Xingsu Yu ◽

Zhenwei Su ◽

...

Keyword(s):

Cancer Therapy ◽

Gene Silencing ◽

Delivery System ◽

Target Gene ◽

Sirna Delivery ◽

Sirna Delivery System

A siRNA delivery system with pH and reduction dual-sensitivity was developed for efficient target gene silencing in cancer therapy.

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Targeted Delivery of siRNA Therapeutics using Ligand Mediated Biodegradable Polymeric Nanocarriers

Current Pharmaceutical Design ◽

10.2174/1381612824666180702113345 ◽

2018 ◽

Vol 24 (16) ◽

pp. 1788-1800 ◽

Cited By ~ 1

Author(s):

Kye-Soo Cho ◽

Seo-Jin Hong ◽

Min-Hye Ahn ◽

Sukdeb Pal ◽

Pill-Hoon Choung ◽

...

Keyword(s):

Cancer Treatment ◽

Delivery System ◽

Targeted Delivery ◽

Sirna Delivery ◽

Public Health Issue ◽

Magic Bullet ◽

Bodily Fluids ◽

Low Cytotoxicity ◽

Genetic And Environmental Factors ◽

Sirna Delivery System

Background: Cancer poses a major public health issue, is linked with high mortality rates across the world, and shows a strong interplay between genetic and environmental factors. To date, common therapeutics, including chemotherapy, immunotherapy, and radiotherapy, have made significant contributions to cancer treatment, although diverse obstacles for achieving the permanent “magic bullet” cure have remained. Recently, various anticancer therapeutic agents designed to overcome the limitations of these conventional cancer treatments have received considerable attention. One of these promising and novel agents is the siRNA delivery system; however, poor cellular uptake and altered siRNA stability in physiological environments have limited its use in clinical trials. Therefore, developing the ideal siRNA delivery system with low cytotoxicity, improved siRNA stability in the body’s circulation, and prevention of its rapid clearance from bodily fluids, is rapidly emerging as an innovative therapeutic strategy to combat cancer. Moreover, active targeting using ligand moieties which bind to over-expressed receptors on the surface of cancer cells would enhance the therapeutic efficiency of siRNA. Conclusion: In this review, we provide 1) an overview of the non-viral carrier associated with siRNA delivery for cancer treatment, and 2) a description of the five major cancer-targeting ligands.

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