Functional Nanostructures for Effective Delivery of Small Interfering RNA Therapeutics

Hong, Cheol Am; Nam, Yoon Sung

doi:10.7150/thno.8491

Cited by 100 publications

(77 citation statements)

References 125 publications

(115 reference statements)

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“…However, the rapid administration of large volumes into the tail vein of mice may lead to tissue damage and stress responses, and this approach is unlikely to be feasible in large animals anyway. Most current work employs nanoparticles to encapsulate siRNA (Hong and Nam 2014) Fig. 1.…”

Section: Administration Of Exogenously Produced Rna Moleculesmentioning

confidence: 99%

“…Amongst these are polymer-based nanoparticles, lipid-based nanoparticles, aggregation of the siRNA itself, and viral and bacterial carriers of RNAi molecules (Lee et al 2013;Dong et al 2014;Hong and Nam 2014). Many examples have shown sufficient promise that they are reaching clinical trials; however, these nanoparticles also have significant drawbacks (Rettig and Behlke 2012).…”

Section: Technologymentioning

confidence: 99%

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RNA interference-based technology: what role in animal agriculture?

et al. 2017

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Abstract. Animal agriculture faces a broad array of challenges, ranging from disease threats to adverse environmental conditions, while attempting to increase productivity using fewer resources. RNA interference (RNAi) is a biological phenomenon with the potential to provide novel solutions to some of these challenges. Discovered just 20 years ago, the mechanisms underlying RNAi are now well described in plants and animals. Intracellular double-stranded RNA triggers a conserved response that leads to cleavage and degradation of complementary mRNA strands, thereby preventing production of the corresponding protein product. RNAi can be naturally induced by expression of endogenous microRNA, which are critical in the regulation of protein synthesis, providing a mechanism for rapid adaptation of physiological function. This endogenous pathway can be co-opted for targeted RNAi either through delivery of exogenous small interfering RNA (siRNA) into target cells or by transgenic expression of short hairpin RNA (shRNA). Potentially valuable RNAi targets for livestock include endogenous genes such as developmental regulators, transcripts involved in adaptations to new physiological states, immune response mediators, and also exogenous genes such as those encoded by viruses. RNAi approaches have shown promise in cell culture and rodent models as well as some livestock studies, but technical and market barriers still need to be addressed before commercial applications of RNAi in animal agriculture can be realised. Key challenges for exogenous delivery of siRNA include appropriate formulation for physical delivery, internal transport and eventual cellular uptake of the siRNA; additionally, rigorous safety and residue studies in target species will be necessary for siRNA delivery nanoparticles currently under evaluation. However, genomic incorporation of shRNA can overcome these issues, but optimal promoters to drive shRNA expression are needed, and genetic engineering may attract more resistance from consumers than the use of exogenous siRNA. Despite these hurdles, the convergence of greater understanding of RNAi mechanisms, detailed descriptions of regulatory processes in animal development and disease, and breakthroughs in synthetic chemistry and genome engineering has created exciting possibilities for using RNAi to enhance the sustainability of animal agriculture.

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Section: Administration Of Exogenously Produced Rna Moleculesmentioning

confidence: 99%

Section: Technologymentioning

confidence: 99%

RNA interference-based technology: what role in animal agriculture?

et al. 2017

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“…A variety of chemical modifications have been developed, and introducing drug delivery system (DDS) leads to greater improvement for delivery of oligonucleotides to targeted organs and cells (3). Especially effective delivery of small interfering RNA (siRNA) in vivo is difficult by itself, and needs some DDS.…”

Section: Introductionmentioning

confidence: 99%

Drug delivery system of therapeutic oligonucleotides

Asami

Yoshioka

Nishina

et al. 2016

DD&T

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“…16 NBs modified with specific agents have been demonstrated as appropriate carriers that can efficiently deliver targeted therapeutic drugs to cells and tissues. [17][18][19][20][21] In the current study, we developed a multifunctional nanocarrier that efficiently combines cancer cell targeting with imaging, thus providing the potential for space-controlled drug release in addition to tumor therapy. In the current study, we selected PLGA polymers in this nanocarrier system due to the diffusion capability and dispersal-controlled drug discharge of this molecule.…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel-loaded and A10-3.2 aptamer-targeted poly(lactide-<em>co</em>-glycolic acid) nanobubbles for ultrasound imaging and therapy of prostate cancer

Wu¹,

Wang²,

Wang³

et al. 2017

IJN

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In the current study, we synthesized prostate cancer-targeting poly(lactide- co -glycolic acid) (PLGA) nanobubbles (NBs) modified using A10-3.2 aptamers targeted to prostate-specific membrane antigen (PSMA) and encapsulated paclitaxel (PTX). We also investigated their impact on ultrasound (US) imaging and therapy of prostate cancer. PTX-A10-3.2-PLGA NBs were developed using water-in-oil-in-water (water/oil/water) double emulsion and carbodiimide chemistry approaches. Fluorescence imaging together with flow cytometry verified that the PTX-A10-3.2-PLGA NBs were successfully fabricated and could specifically bond to PSMA-positive LNCaP cells. We speculated that, in vivo, the PTX-A10-3.2-PLGA NBs would travel for a long time, efficiently aim at prostate cancer cells, and sustainably release the loaded PTX due to the improved permeability together with the retention impact and US-triggered drug delivery. The results demonstrated that the combination of PTX-A10-3.2-PLGA NBs with low-frequency US achieved high drug release, a low 50% inhibition concentration, and significant cell apoptosis in vitro. For mouse prostate tumor xenografts, the use of PTX-A10-3.2-PLGA NBs along with low-frequency US achieved the highest tumor inhibition rate, prolonging the survival of tumor-bearing nude mice without obvious systemic toxicity. Moreover, LNCaP xenografts in mice were utilized to observe modifications in the parameters of PTX-A10-3.2-PLGA and PTX-PLGA NBs in the contrast mode and the allocation of fluorescence-labeled PTX-A10-3.2-PLGA and PTX-PLGA NBs in live small animals and laser confocal scanning microscopy fluorescence imaging. These results demonstrated that PTX-A10-3.2-PLGA NBs showed high gray-scale intensity and aggregation ability and showed a notable signal intensity in contrast mode as well as aggregation ability in fluorescence imaging. In conclusion, we successfully developed an A10-3.2 aptamer and loaded PTX-PLGA multifunctional theranostic agent for the purpose of obtaining US images of prostate cancer and providing low-frequency US-triggered therapy of prostate cancer that was likely to constitute a strategy for both prostate cancer imaging and chemotherapy.

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Functional Nanostructures for Effective Delivery of Small Interfering RNA Therapeutics

Cited by 100 publications

References 125 publications

RNA interference-based technology: what role in animal agriculture?

RNA interference-based technology: what role in animal agriculture?

Drug delivery system of therapeutic oligonucleotides

Paclitaxel-loaded and A10-3.2 aptamer-targeted poly(lactide-<em>co</em>-glycolic acid) nanobubbles for ultrasound imaging and therapy of prostate cancer

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