Design, fabrication and applications of tetrahedral DNA nanostructure-based multifunctional complexes in drug delivery and biomedical treatment

Zhang, Tao; Tian, Taoran; Zhou, Ronghui; Li, Songhang; Ma, Wenjuan; Zhang, Yuxin; Liu, Nanxin; Shi, Sirong; Li, Qianshun; Xie, Xueping; Ge, Yichen; Liu, Mengting; Zhang, Qi; Lin, Shiyu; Cai, Xiaoxiao; Lin, Yunfeng

doi:10.1038/s41596-020-0355-z

Cited by 220 publications

(211 citation statements)

References 56 publications

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“…The synthesis of the tFNAs is described in a previous study [ 25 , 26 ]. In brief, four specific single-strand DNA (ssDNA) strands (Table S1) were added to a Tris–HCl and MgCl 2 (TM) buffer at an equivalent molar ratio, heated to 95 °C for 10 min, and cooled to 4 °C for 20 min.…”

Section: Methodsmentioning

confidence: 99%

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Tetrahedral Framework Nucleic Acid-Based Delivery of Resveratrol Alleviates Insulin Resistance: From Innate to Adaptive Immunity

Gao

Shi

et al. 2021

Nano-Micro Lett.

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Obesity-induced insulin resistance is the hallmark of metabolic syndrome, and chronic, low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells. Current therapeutic approaches lack efficacy and immunomodulatory capacity. Thus, a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance. Here, we synthesized a tetrahedral framework nucleic acid (tFNA) nanoparticle that carried resveratrol (RSV) to inhibit tissue inflammation and improve insulin sensitivity in obese mice. The prepared nanoparticles, namely tFNAs-RSV, possessed the characteristics of simple synthesis, stable properties, good water solubility, and superior biocompatibility. The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy. In high-fat diet (HFD)-fed mice, the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status. tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages. As for adaptive immunity, the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg, leading to the alleviation of insulin resistance. Furthermore, this study is the first to demonstrate that tFNAs, a nucleic acid material, possess immunomodulatory capacity. Collectively, our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice, suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.

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Section: Methodsmentioning

confidence: 99%

“…The synthesis of the tFNAs is described in a previous study [25,26]. In brief, four specific single-strand DNA (ssDNA) 1 3…”

Section: Tfnasmentioning

confidence: 99%

Tetrahedral Framework Nucleic Acid-Based Delivery of Resveratrol Alleviates Insulin Resistance: From Innate to Adaptive Immunity

Gao

Shi

et al. 2021

Nano-Micro Lett.

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“…The tetrahedral skeleton nucleic acids (tFNAs), as a new 3D nucleic acid nanomaterial with considerable merits, including biocompatibility, structural stability, and programmability, have demonstrated tremendous potential as a vector for drug delivery and biomedical treatment. [ 20–24 ] In our early exploration in the prevention and treatment of various eye diseases, tFNAs have been proved to act a positive part as drugs in repairing corneal injury and the anti‐oxidative stress of RGCs. [ 25,26 ] Furthermore, our previous studies have shown that tFNAs can exert neuroprotective influence in the Alzheimer's disease in vitro model.…”

Section: Introductionmentioning

confidence: 99%

The Neuroprotective Effect of MicroRNA‐22‐3p Modified Tetrahedral Framework Nucleic Acids on Damaged Retinal Neurons Via TrkB/BDNF Signaling Pathway

Xiao

Yan

et al. 2021

Adv Funct Materials

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Glaucoma is the world's leading irreversible cause of blindness. It is characterized by progressive retinal ganglion cells (RGCs) loss and axon damage, and there is no effective prevention or treatment so far. In this study, tetrahedral frame nucleic acids (tFNAs) with various biological functions are selected as the carrier, and microRNA‐22‐3p (miR‐22) are modified by attaching them onto tFNAs to synthesize a novel DNA nanocomplex (tFNAs‐miR22). Relevant results show that tFNAs can efficiently transfer miR‐22 into damaged retinal neurons to impose a neuroprotective effect on glaucoma. More interestingly, a certain synergism between tFNAs and miR‐22 is shown. tFNAs‐miR22 can selectively activate tyrosine kinase receptor B (TrkB) and regulate the TrkB‐brain‐derived growth factor (BDNF) signaling pathway to restore the expression of BDNF on the models of N‐methyl‐D‐aspartate (NMDA)‐induced glaucoma in vivo and in vitro, thus exerting the neuroprotective effect on retinal neurons. This study shows the successfully establishment of a simple but effective delivery system of microRNAs associated with glaucoma treatment, which may be a promising neuroprotective agent for future treatment of this optic neurodegenerative disease.

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“…At the mass ratio of 50:1, the anti‐fungal effect of the complex decreased instead. Previous studies showed that TDNs can be internalized by cells and bacteria as the small‐weight‐drug vehicles 23,24 . We considered that the increased negative surface charges of the complex with more TDNs would weaken the electrostatic attraction between TDN/His‐5 and cell membrane, leading to decreased transport efficiency.…”

Section: Resultsmentioning

confidence: 99%

“…Despite the polyanionic nature of DNA, TDNs can be internalized via endocytosis and transported into lysosomes in a microtubule‐dependent manner 26,27 . Accordingly, TDN‐based drug delivery has been proposed and researched extensively at the cellular and bacterial levels over the past decade 24,28,29 . From previous studies, TDNs have yielded satisfactory results as delivery vehicles attached with low‐molecular‐weight drugs like nucleic acids, antibiotics and peptides 28,30,31 .…”

Section: Introductionmentioning

confidence: 99%

Tetrahedral DNA nanostructure improves transport efficiency and anti‐fungal effect of histatin 5 against Candida albicans

et al. 2021

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Objectives Anti‐microbial peptides (AMPs) have been comprehensively investigated as a novel alternative to traditional antibiotics against microorganisms. Meanwhile, Tetrahedral DNA nanostructures (TDNs) have gained attention in the field of biomedicine for their premium biological effects and transportation efficiency as delivery vehicles. Hence, in this study, TDN/Histatin 5 (His‐5) was synthesized and the transport efficiency and anti‐fungal effect were measured to evaluate the promotion of His‐5 modified by TDNs. Materials and Methods Tetrahedral DNA nanostructures/His‐5 complex was prepared via electrostatic attraction and characterized by transmission electron microscopy (TEM), polyacrylamide gel electrophoresis (PAGE), dynamic light scattering (DLS) and electrophoretic light scattering (ELS). The anti‐fungal effect of the TDN/His‐5 complex was evaluated by determining the growth curve and colony‐forming units of C. albicans. The morphological transformation of C. albicans was observed by light microscope and scanning electron microscope (SEM). Immunofluorescence was performed, and potassium efflux was detected to mechanistically demonstrate the efficacy of TDN/His‐5. Results The results showed that Histatin 5 modified by TDNs had preferable stability in serum and was effectively transported into C. albicans, leading to the increased formation of intracellular reactive oxygen species, higher potassium efflux and enhanced anti‐fungal effect against C. albicans. Conclusions Our study showed that TDN/His‐5 was synthesized successfully. And by the modification of TDNs, His‐5 showed increased transport efficiency and improved anti‐fungal effect.

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Design, fabrication and applications of tetrahedral DNA nanostructure-based multifunctional complexes in drug delivery and biomedical treatment

Cited by 220 publications

References 56 publications

Tetrahedral Framework Nucleic Acid-Based Delivery of Resveratrol Alleviates Insulin Resistance: From Innate to Adaptive Immunity

Tetrahedral Framework Nucleic Acid-Based Delivery of Resveratrol Alleviates Insulin Resistance: From Innate to Adaptive Immunity

The Neuroprotective Effect of MicroRNA‐22‐3p Modified Tetrahedral Framework Nucleic Acids on Damaged Retinal Neurons Via TrkB/BDNF Signaling Pathway

Tetrahedral DNA nanostructure improves transport efficiency and anti‐fungal effect of histatin 5 against Candida albicans

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