An Amphiphilic Dendrimer for Effective Delivery of Small Interfering RNA and Gene Silencing In Vitro and In Vivo

2012 ◽  
Vol 124 (34) ◽  
pp. 8606-8612 ◽  
Author(s):  
Tianzhu Yu ◽  
Xiaoxuan Liu ◽  
Anne-Laure Bolcato-Bellemin ◽  
Yang Wang ◽  
Cheng Liu ◽  
...  
2012 ◽  
Vol 51 (34) ◽  
pp. 8478-8484 ◽  
Author(s):  
Tianzhu Yu ◽  
Xiaoxuan Liu ◽  
Anne-Laure Bolcato-Bellemin ◽  
Yang Wang ◽  
Cheng Liu ◽  
...  

2020 ◽  
Vol 6 (30) ◽  
pp. eaba5379 ◽  
Author(s):  
Md. Nazir Hossen ◽  
Lin Wang ◽  
Harisha R. Chinthalapally ◽  
Joe D. Robertson ◽  
Kar-Ming Fung ◽  
...  

Gene silencing using small-interfering RNA (siRNA) is a viable therapeutic approach; however, the lack of effective delivery systems limits its clinical translation. Herein, we doped conventional siRNA-liposomal formulations with gold nanoparticles to create “auroliposomes,” which significantly enhanced gene silencing. We targeted MICU1, a novel glycolytic switch in ovarian cancer, and delivered MICU1-siRNA using three delivery systems—commercial transfection agents, conventional liposomes, and auroliposomes. Low-dose siRNA via transfection or conventional liposomes was ineffective for MICU1 silencing; however, in auroliposomes, the same dose gave >85% gene silencing. Efficacy was evident from both in vitro growth assays of ovarian cancer cells and in vivo tumor growth in human ovarian cell line—and patient-derived xenograft models. Incorporation of gold nanoparticles shifted intracellular uptake pathways such that liposomes avoided degradation within lysosomes. Auroliposomes were nontoxic to vital organs. Therefore, auroliposomes represent a novel siRNA delivery system with superior efficacy for multiple therapeutic applications.


2010 ◽  
Vol 52 (8) ◽  
pp. 693-699 ◽  
Author(s):  
Taro Adachi ◽  
Emi Kawakami ◽  
Naozumi Ishimaru ◽  
Takahiro Ochiya ◽  
Yoshio Hayashi ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-24 ◽  
Author(s):  
Chong-Su Cho

Polyethylenimine (PEI), considered as the most potent and promising alternative carrier to viral vectors, has been studied as the “state of the art” among various polymers for nonviral gene delivery applications for many years. Although PEI-based carrier minimizes the bottlenecks associated with viral vectors such as unwanted immunogenicity and production problems, the toxic side effects of PEI prevent its rapid advancements due to nondegradable nature. In this regard, various degradable cross-linking and/or grafting agents have been linked to synthesize degradable PEIs in order to minimize the toxicity and improve the efficacy of PEI-mediated gene carriers. This paper describes an update on various cross-linkers and grafting agents in the design and development of degradable PEI derivatives and their potential applications for effective delivery of DNA in vitro and in vivo. The molecular weight (MW) of PEI and the structural relationship to its cellular toxicity and transfection ability were also discussed. Finally, the potential applications of various degradable PEIs for small interfering RNA (siRNA)-mediated gene silencing were also covered.


Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2570 ◽  
Author(s):  
Inés Serrano-Sevilla ◽  
Álvaro Artiga ◽  
Scott G. Mitchell ◽  
Laura De Matteis ◽  
Jesús M. de la Fuente

Natural polysaccharides are frequently used in the design of drug delivery systems due to their biocompatibility, biodegradability, and low toxicity. Moreover, they are diverse in structure, size, and charge, and their chemical functional groups can be easily modified to match the needs of the final application and mode of administration. This review focuses on polysaccharidic nanocarriers based on chitosan and hyaluronic acid for small interfering RNA (siRNA) delivery, which are highly positively and negatively charged, respectively. The key properties, strengths, and drawbacks of each polysaccharide are discussed. In addition, their use as efficient nanodelivery systems for gene silencing applications is put into context using the most recent examples from the literature. The latest advances in this field illustrate effectively how chitosan and hyaluronic acid can be modified or associated with other molecules in order to overcome their limitations to produce optimized siRNA delivery systems with promising in vitro and in vivo results.


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