Tetrahedral Framework Nucleic Acids Loaded with Aptamer AS1411 for siRNA Delivery and Gene Silencing in Malignant Melanoma

Xiao, Dexuan; Li, Yanjing; Tian, Taoran; Zhang, Tianxu; Shi, Sirong; Lu, Boyao; Gao, Yang; Xin, Qin; Zhang, Mei; Wei, Wei; Lin, Yunfeng

doi:10.1021/acsami.0c23005

Cited by 55 publications

(41 citation statements)

References 57 publications

(79 reference statements)

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“…[ 27 ] Due to their editability, biocompatibility and hypotoxicity, tFNA can be utilized as a flexible delivery vehicles in the anti‐tumor, [ 28 ] active targeting therapies [ 29 ] and silencing genes. [ 30 ]…”

Section: Introductionmentioning

confidence: 99%

“…[27] Due to their editability, biocompatibility and hypotoxicity, tFNA can be utilized as a flexible delivery vehicles in the anti-tumor, [28] active targeting therapies [29] and silencing genes. [30] Herein, we report a novel DNA nano-drug named tFNA-siCCR2, which has siCCR2 attached to a special functional tFNA and rescued the neurological dysfunction following ICH. Mechanistically, tFNA-siCCR2 was internalized by BV2 cells and then significantly attenuated CCR2 gene expression and protein level, and promoted an M1 to M2 phenotypic switch.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic siCCR2 Loaded by Tetrahedral Framework DNA Nanorobotics in Therapy for Intracranial Hemorrhage

et al. 2021

Adv Funct Materials

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Modulating microglial polarization is a potential strategy to assuage secondary brain injury caused by intracranial hemorrhage (ICH). However, despite decades of effort, effective therapies targeting microglia for ICH are still lacking. Here, a nanorobotic, tetrahedral framework nucleic acid (tFNA), is successfully synthesized and designed to carry C‐C chemokine receptor 2 (siCCR2) for use in in vitro hemin‐induced and in vivo collagenase‐induced ICH models. This nanoscale complex (tFNA‐siCCR2), which possesses biocompatibility, editability, and structural stability, exhibits a favorable effect in inhibiting the expression of CCR2. After treatment with tFNA‐siCCR2, hematoma absorption is accelerated, and neurological inflammation is mitigated by decreasing levels of proinflammatory cytokines, while increasing the release of anti‐inflammatory factors. Consequently, the neurological deficits of mice with ICH improve. These results indicate that inhibiting CCR2 expression during the acute phase of ICH polarizes microglia towards a therapeutic subtype, and restores neurological function, which demonstrates that tFNA has a promising ability to transfer siCCR2 for treating ICH.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Therapeutic siCCR2 Loaded by Tetrahedral Framework DNA Nanorobotics in Therapy for Intracranial Hemorrhage

et al. 2021

Adv Funct Materials

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“…AS1411 has been linked to various types of nanoparticles due to its selective binding to nucleolin, a protein overexpressed on the cell surface and inside cancer cells [45][46][47][48][49]. Notably, a marked improvement of cytotoxicity has been previously obtained by increasing the loading (more than 100 molecules) of AS1411 on the surface of gold nanostars [50].…”

Section: Discussionmentioning

confidence: 99%

AS1411 Aptamer Linked to DNA Nanostructures Diverts Its Traffic Inside Cancer Cells and Improves Its Therapeutic Efficacy

et al. 2021

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The nucleolin-binding G-quadruplex AS1411 aptamer has been widely used for cancer therapy and diagnosis and linked to nanoparticles for its selective targeting activity. We applied a computational and experimental integrated approach to study the effect of engineering AS1411 aptamer on an octahedral truncated DNA nanocage to obtain a nanostructure able to combine selective cancer-targeting and anti-tumor activity. The nanocages functionalized with one aptamer molecule (Apt-NC) displayed high stability in serum, were rapidly and selectively internalized in cancer cells through an AS1411-dependent mechanism, and showed over 200-fold increase in anti-cancer activity when compared with the free aptamer. Comparison of Apt-NCs and free AS1411 intracellular distribution showed that they traffic differently inside cells: Apt-NCs distributed through the endo-lysosomal pathway and were never found in the nuclei, while the free AS1411 was mostly found in the perinuclear region and in nucleoli. Molecular dynamics simulations indicated that the aptamer, when linked to the nanocage, sampled a limited conformational space, more confined than in the free state, which is characterized by a large number of metastable conformations. A different intracellular trafficking of Apt-NCs compared with free aptamer and the confined aptamer conformations induced by the nanocage were likely correlated with the high cytotoxic enhancement, suggesting a structure–function relationship for the AS1411 aptamer activity.

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“…As mentioned previously (Chen et al, 2015), the formed system with tube-like features also exhibits a high aspect ratio, which permits efficient endosomal escape to facilitate the release of RNA in the cytoplasm (Ren et al, 2016). In addition to nucleotidebased targeting agents such as the DNA primer hairpin mentioned above and the most widely applied AS1411 aptamer (Lin et al, 2020;Xiao et al, 2021), the chemical targeting ligand folate (Liu J. et al, 2021) and redox-sensitive disulfide bonds (Wang H. et al, 2021) have also been applied to improve the specific intracellular delivery and controlled release of RNAs. In these systems, peptides including influenza hemagglutinin peptide and transactivator of transcription peptide are added to improve the endosomal escape (Liu S. et al, 2021) and intratumoral delivery of RNAs (Wang Z. et al, 2021).…”

Section: Dna Assembliesmentioning

confidence: 98%

RNA Drug Delivery Using Biogenic Nanovehicles for Cancer Therapy

Sun²,

et al. 2021

Front. Pharmacol.

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RNA-based therapies have been promising method for treating all kinds of diseases, and four siRNA-based drugs and two mRNA-based drugs have been approved and are on the market now. However, none of them is applied for cancer treatment. This is not only because of the complexity of the tumor microenvironment, but also due to the intrinsic obstacles of RNAs. Until now, all kinds of strategies have been developed to improve the performance of RNAs for cancer therapy, especially the nanoparticle-based ones using biogenic materials. They are much more compatible with less toxicity compared to the ones using synthetic polymers, and the most widely studied biogenic materials are oligonucleotides, exosomes, and cell membranes. Particular characteristics make them show different capacities in internalization and endosomal escape as well as specific targeting. In this paper, we systematically summarize the RNA-based nano-delivery systems using biogenic materials for cancer therapy, and we believe this review will provide a valuable reference for researchers involved in the field of biogenic delivery and RNA-based therapies for cancer treatment.

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Tetrahedral Framework Nucleic Acids Loaded with Aptamer AS1411 for siRNA Delivery and Gene Silencing in Malignant Melanoma

Cited by 55 publications

References 57 publications

Therapeutic siCCR2 Loaded by Tetrahedral Framework DNA Nanorobotics in Therapy for Intracranial Hemorrhage

Therapeutic siCCR2 Loaded by Tetrahedral Framework DNA Nanorobotics in Therapy for Intracranial Hemorrhage

AS1411 Aptamer Linked to DNA Nanostructures Diverts Its Traffic Inside Cancer Cells and Improves Its Therapeutic Efficacy

RNA Drug Delivery Using Biogenic Nanovehicles for Cancer Therapy

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