DNA nanoclew templated spherical nucleic acids for siRNA delivery

Ruan, Weimin; Zheng, Meng; An, Yang; Liu, Yuanyuan; Lovejoy, David B.; Hao, Mingcong; Zou, Yan; Lee, Albert; Yang, Shu; Lu, Yiqing; Morsch, Marco; Chung, Roger S.; Shi, Bingyang

doi:10.1039/c7cc09257a

Cited by 57 publications

(52 citation statements)

References 42 publications

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“…Finally, a novel approach with high potential is the use of DNA scaffolds for the delivery of siRNA 165. For example, DNA dumbbell,166 DNA nanoribbons,167 and spherical nucleic acids (SNA)168 have been described as alternative systems which are biodegradable, non-toxic, and also non-immunogenic. These DNA scaffolds have proved to be effective when have incorporated targeting ligands, siRNA drugs as well as chemotherapeutic drugs with high precision 169,170…”

Section: Limitations To the Sirna Therapeutic Approachmentioning

confidence: 99%

<p>Small interfering RNAs (siRNAs) in cancer therapy: a nano-based approach</p>

Chalbatani¹,

Dana²,

Gharagouzloo³

et al. 2019

IJN

188

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Cancer is one of the most complex diseases that has resulted in multiple genetic disorders and cellular abnormalities. Globally, cancer is the most common health concern disease that is affecting human beings. Great efforts have been made over the past decades in biology with the aim of searching novel and more efficient tools in therapy. Thus, small interfering RNAs (siRNAs) have been considered one of the most noteworthy developments which are able to regulate gene expression following a process known as RNA interference (RNAi). RNAi is a post-transcriptional mechanism that involves the inhibition of gene expression through promoting cleavage on a specific area of a target messenger RNA (mRNA). This technology has shown promising therapeutic results for a good number of diseases, especially in cancer. However, siRNA therapeutics have to face important drawbacks in therapy including stability and successful siRNA delivery in vivo. In this regard, the development of effective siRNA delivery systems has helped addressing these issues by opening novel therapeutic windows which have allowed to build up important advances in Nanomedicine. In this review, we discuss the progress of siRNA therapy as well as its medical application via nanoparticle-mediated delivery for cancer treatment.

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Section: Limitations To the Sirna Therapeutic Approachmentioning

confidence: 99%

<p>Small interfering RNAs (siRNAs) in cancer therapy: a nano-based approach</p>

Chalbatani¹,

Dana²,

Gharagouzloo³

et al. 2019

IJN

188

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“…This charge and hydrogen bond competition leads to further 3I‐NM@siRNA decomposition after the hydrophobic interaction is lost, resulting in effective release of encapsulated siRNA. To more fully investigate ROS response in vitro, fluorescence resonance energy transfer (FRET) assay was utilized as reported before . As shown in Figure D, initial take up of 2I‐NM@siRNA and 3I‐NM@siRNA by U87MG cells after 1 h, obvious Cy3 (green) and Cy5 (red) signals, can be detected, arising from Cy3/Cy5‐ siRNA FRET effect, with colocalization of Cy3 and Cy5 yielding yellow dots.…”

mentioning

confidence: 99%

ROS‐Responsive Polymeric siRNA Nanomedicine Stabilized by Triple Interactions for the Robust Glioblastoma Combinational RNAi Therapy

et al. 2019

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Most brain diseases including brain tumor and dementia are fatal without current therapeutic solutions. [1] Small interfering RNA (siRNA) technology has demonstrated inherent advantages and significant potential for treating numerous tumor types, [2] owing to its high specificity, low dose requirement and relatively simple drug development process. [3] The rapid development of nanotechnology and material sciences has led to a myriad of nanocarriers being explored for siRNA delivery, [4] and promoting the preclinical potential of siRNA in treating genetically based diseases. siRNA delivery carriers, such as cationic polymers, [5] are predominately amine-abundant and can compress siRNAs into nanoparticles via electrostatic interaction between positive-charged amine groups (NH 3 + ) of polymer and negative-charged phosphate group (PO 3 4− ) of siRNA. However, the abundant presence of charged biomacromolecules in blood, can interfere with the association between cationic polymers and siRNAs, [6] making siRNA nanomedicines that solely rely on electrostatic interaction for stabilization at risk of dissociation in vivo, thereby Small interfering RNA (siRNA) holds inherent advantages and great potential for treating refractory diseases. However, lack of suitable siRNA delivery systems that demonstrate excellent circulation stability and effective at-site delivery ability is currently impeding siRNA therapeutic performance. Here, a polymeric siRNA nanomedicine (3I-NM@siRNA) stabilized by triple interactions (electrostatic, hydrogen bond, and hydrophobic) is constructed. Incorporating extra hydrogen and hydrophobic interactions significantly improves the physiological stability compared to an siRNA nanomedicine analog that solely relies on the electrostatic interaction for stability. The developed 3I-NM@siRNA nanomedicine demonstrates effective at-site siRNA release resulting from tumoral reactive oxygen species (ROS)-triggered sequential destabilization. Furthermore, the utility of 3I-NM@siRNA for treating glioblastoma (GBM) by functionalizing 3I-NM@siRNA nanomedicine with angiopep-2 peptide is enhanced. The targeted Ang-3I-NM@siRNA exhibits superb blood-brain barrier penetration and potent tumor accumulation. Moreover, by cotargeting polo-like kinase 1 and vascular endothelial growth factor receptor-2, Ang-3I-NM@ siRNA shows effective suppression of tumor growth and significantly improved survival time of nude mice bearing orthotopic GBM brain tumors. New siRNA nanomedicines featuring triple-interaction stabilization together with inbuilt self-destruct delivery ability provide a robust and potent platform for targeted GBM siRNA therapy, which may have utility for RNA interference therapy of other tumors or brain diseases. siRNA DeliveryThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.

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“…DNA nanoclews are a class of nucleic acid nanostructures synthesized by rolling circle amplification (RCA). Because of its high biocompatibility, predictability, programmability and simplicity to functionalization, DNA nanoclews have been developed as vehicles for drug delivery 264 and gene delivery 265 . A yarn-like DNA nanoclew was synthesized by RCA with palindromic sequences encoded to be partially complementary to sgRNA in the RNP complex.…”

Section: Materials For Rnp Deliverymentioning

confidence: 99%

Strategies in the delivery of Cas9 ribonucleoprotein for CRISPR/Cas9 genome editing

Song¹,

Shen²,

Li³

et al. 2021

Theranostics

274

184

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CRISPR/Cas9 genome editing has gained rapidly increasing attentions in recent years, however, the translation of this biotechnology into therapy has been hindered by efficient delivery of CRISPR/Cas9 materials into target cells. Direct delivery of CRISPR/Cas9 system as a ribonucleoprotein (RNP) complex consisting of Cas9 protein and single guide RNA (sgRNA) has emerged as a powerful and widespread method for genome editing due to its advantages of transient genome editing and reduced off-target effects. In this review, we summarized the current Cas9 RNP delivery systems including physical approaches and synthetic carriers. The mechanisms and beneficial roles of these strategies in intracellular Cas9 RNP delivery were reviewed. Examples in the development of stimuli-responsive and targeted carriers for RNP delivery are highlighted. Finally, the challenges of current Cas9 RNP delivery systems and perspectives in rational design of next generation materials for this promising field will be discussed.

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DNA nanoclew templated spherical nucleic acids for siRNA delivery

Cited by 57 publications

References 42 publications

<p>Small interfering RNAs (siRNAs) in cancer therapy: a nano-based approach</p>

<p>Small interfering RNAs (siRNAs) in cancer therapy: a nano-based approach</p>

ROS‐Responsive Polymeric siRNA Nanomedicine Stabilized by Triple Interactions for the Robust Glioblastoma Combinational RNAi Therapy

Strategies in the delivery of Cas9 ribonucleoprotein for CRISPR/Cas9 genome editing

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