Cationic Lipid-Coated Gold Nanoparticles as Efficient and Non-Cytotoxic Intracellular siRNA Delivery Vehicles

Kong, Wh Kong Won Ho; Bae, Ki Hyun; Jo, Sd Jo Sung Duk; Kim, Js Kim Jee Seon; Park, Tg Park Tae Gwan

doi:10.1007/s11095-011-0554-y

Cited by 64 publications

(36 citation statements)

References 38 publications

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Section: Sirna-gold Nanoparticlesmentioning

confidence: 99%

“…Many examples of silencing have used luciferase activity as an indicator of success [25,29,38,45,46].…”

Section: The Protein Levelmentioning

confidence: 99%

“…As GFP is not a native protein, it has limited used for further studies, which would ideally aim at altering native protein levels by using silencing machinery, such as siRNA, miRNA or small molecules [24,25,38]. When verifying protein knockdown, alternative techniques would need to be used such as western blots [143], flow cytometry [45] and In-Cell westerns [144]. A recent study by Zhao et al reported the development of AuNPs loaded with siRNA against the epidermal growth factor receptor (EGFR) gene, and observed a knockdown efficiency of between 16-38% in MCF- 7 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 REVIEW NANO TODAY 33 cells via flow cytometry (Figure 16) [145].…”

Section: The Protein Levelmentioning

confidence: 99%

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15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

et al. 2015

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RNAi has always captivated scientists due to its tremendous power to modulate the phenotype of living organisms. This natural and powerful biological mechanism can now be harnessed to downregulate specific gene expression in diseased cells; opening up endless opportunities. Since most of the conventional siRNA delivery methods are limited by a narrow therapeutic index and significant side and off-target effects, we are now in the dawn of a new age in gene therapy driven by nanotechnology vehicles for RNAi therapeutics. Here, we outlook the "do's and dont's" of the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 REVIEW NANO TODAY 2 inorganic RNAi nanomaterials developed in the last 15 years and the different strategies employed are compared and scrutinized, offering important suggestions for the next 15. *Manuscript Click here to view linked References

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Section: Sirna-gold Nanoparticlesmentioning

confidence: 99%

“…Many examples of silencing have used luciferase activity as an indicator of success [25,29,38,45,46].…”

Section: The Protein Levelmentioning

confidence: 99%

Section: The Protein Levelmentioning

confidence: 99%

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15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

et al. 2015

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“…Various promising nanoparticles (NPs) strategies that have been successful in depicting in vitro gene silencing and tumor reduction efficacy in animal models, safety in non-human primates and in few cases, have undergone clinical trial testing include, (A) Lipid based NPs: liposomes [16], lipoplexes [17,18], stable nucleic acid lipid nanoparticles (SNALP) [19,20] & lipidoid [21], polycation liposomes [22,23], (B) Polymeric NPs: both natural and synthetic, includes cyclodextrin [24], chitosan [25], PLGA [26], polymeric micelles [27], PEI [28] & dendrimers [29], (C) Inorganic NPs: calcium phosphate CaP [30], (D) Carbon-based materials, carbon nanotubes (SWNTs, MWNTs) [31,32], (E) Metal nanoparticles -Gold (Au) [33], Quantum dots (QDs) [34], silicon-based nanoparticles (MSNPs) [35] & super paramagnetic iron oxide nanoparticles (SPIONs) [36] etc. In addition to this, atelocollagen-based delivery strategy also proved to be successful in few cases [37,38].…”

Section: Nanotechnology-based Delivery Strategiesmentioning

confidence: 99%

RNAi-based Cancer Therapeutics: Are we there yet?

Saxena¹

2014

J Pharmacovigil

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RNAi-based therapeutics remains one of the most promising strategies for the effective cancer treatment due to its high target-specificity, precise mechanism of action, greater potency and reduced side effects. Although, tremendous progress and advances have been made in the past few years to develop nanotechnology-based efficient non-viral delivery systems, there are still many hurdles and challenges that must be conquered to achieve the target of clinically relevant formulation in terms of safety, specificity and efficacy.

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“…79 Furthermore, gold nanoparticles have been used in clinical diagnostics and therapeutics, such as cancer, tuberculosis, Alzheimer's disease, HIV, and sciatic nerve repair.…”

mentioning

confidence: 99%

Progress on RNAi-based molecular medicines

Chen¹,

Xie²

2012

IJN

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RNA interference (RNAi) is a promising strategy to suppress the expression of disease-relevant genes and induce post-transcriptional gene silencing. Their simplicity and stability endow RNAi with great advantages in molecular medicine. Several RNAi-based drugs are in various stages of clinical investigation. This review summarizes the ongoing research endeavors on RNAi in molecular medicine, delivery systems for RNAi-based drugs, and a compendium of RNAi drugs in different stages of clinical development. Of special interest are RNAi-based drug target discovery and validation, delivery systems for RNAi-based drugs, such as nanoparticles, rabies virus protein-based vehicles, and bacteriophages for RNA packaging. Keywords: RNA interference, delivery systems, liposome, nanoparticle, molecular medicines Overview of RNA interferenceRNA plays key roles in organisms beyond the traditional role of being a messenger bridging genetic information and biosynthesis of protein. Endogenous or exogenous double-stranded RNA can be cleaved into 21-23-nucleotide small interfering RNA (siRNA) by the endonuclease, Dicer. siRNA can unzip into a guide strand and a passenger strand. The latter will be subsequently degraded. The guide strand is then incorporated into the RNA-induced silencing complex and binds to the target mRNA, inducing mRNA degradation by Argonaute, a component of the RNA-induced silencing complex which affects protein synthesis (Figure 1). This phenomenon is known as RNA interference (RNAi) 1-4 and is well established in diverse organisms. There are three major types of small RNA used to silence gene function by RNAi technology, ie, microRNA (miRNA), siRNA, and short hairpin RNAs (shRNA). 5,6 Although all small RNAs are 22-24 nucleotides in length, [7][8][9] there are some important differences between them. First, siRNA, processed from exogenously introduced strictly base-paired siRNA duplexes, are completely complementary to their target mRNA and facilitate cleavage of bases 10-12 at the 5′ end of the guide strand, 10,11 resulting in transient silence of the target gene. Second, shRNA, inserting in a Pol III expression cassette, can be transfected or packaged into a recombinant virus and introduced into target cells. 5 The advantage of shRNA is prolonged expression of the RNAi effect. Third, miRNA or chimeric miRNA/shRNA, derived from endogenously encoded shRNAs, 5 can mediate gene silencing post-transcriptionally, and bind partially to complementary miRNA target sequences located in the 3′ untranslated regions of target mRNAs, 9 but the "seed" region located in bases 2-8 is highly complementary. 12 The seed region can RNAi as a tool for discovery of drug targetsMost drugs function via blocking of their targets. The simplicity and stability of RNAi in gene silencing make it a powerful tool in drug research and development.16 RNAi-based drug target discovery includes the following steps. Identification of target genesThe selection of target gene is crucial and, to great extent, determines whether subse...

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Cationic Lipid-Coated Gold Nanoparticles as Efficient and Non-Cytotoxic Intracellular siRNA Delivery Vehicles

Abstract: We demonstrated that cationic lipid-coated gold nanoparticles could be widely utilized as efficient and safe siRNA nanocarriers for diverse therapeutic and diagnostic applications.

Cited by 64 publications

References 38 publications

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

RNAi-based Cancer Therapeutics: Are we there yet?

Progress on RNAi-based molecular medicines

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