Ultrasound exposure enhances cellular uptake of nanoscale cargos

DNA nanotechnology utilizes DNA as a structural molecule to design palette of nanostructures with different shapes and sizes. DNA nanocages have demonstrated significant potential for drug delivery. Therefore, enhancing the delivery of DNA nanocages into cells can improve their efficacy as drug delivery agents. Numerous studies have reported the effects of ultrasound for enhancing drug delivery across biological barriers. The mechanical bioeffects caused by cell-ultrasound interaction can cause sonoporation, leading to enhanced uptake of drugs, nanoparticles, and chemotherapeutic agents through membranes. Whether ultrasound exposure can enhance the delivery of DNA nanocages has not been explored, which is the focus of this study. Specifically, we investigated the effects of ultrasound on the cellular uptake of propidium Iodide, fluorescent dextrans, and DNA nanostructures). We provide evidence of modulation of pore formation in the cell membrane by ultrasound by studying the intracellular uptake of the impermeable dye, propidium iodide. Treatment of cells with low amplitudes of ultrasound enhanced the uptake of different sizes of dextrans and DNA based nanodevices. These findings could serve as the foundation for further development ultrasound-enabled DNA nanostructure delivery and for specific understanding of underlying biological mechanisms of interaction between ultrasound parameters and cellular components; the knowledge that can be further explored for potential biological and biomedical applications.

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Advances in DNA Nanostructure-Based Smart Drug Delivery Systems

Nano LIFE ◽

10.1142/s1793984417300011 ◽

2017 ◽

Vol 07 (01) ◽

pp. 1730001 ◽

Cited By ~ 2

Author(s):

Xingjie Hu ◽

Zejun Wang ◽

Chunhai Fan ◽

Haiyun Song

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Water Solubility ◽

Dna Nanotechnology ◽

Delivery Systems ◽

Structure Design ◽

Dna Nanostructures ◽

Cellular Delivery ◽

Nanoscale Systems ◽

Dna Nanostructure

Highly specific deoxyribonucleic acid (DNA) base-pairing not only carries genetic information, but also provides the basis for self-assembly of novel nanostructures with programmable shapes and sizes. Unlike single-stranded and double-stranded DNA, DNA nanostructures exhibit good cellular permeability. They also have characteristics of uniform size, easy functionalization, precise addressability, excellent water solubility and high biocompatibility. Due to their unique properties, these tailored molecular devices are ideal nanoscale systems for targeting cells and triggering cellular responses. Recent progress in the field of DNA nanotechnology has demonstrated effectiveness and advantages of DNA nanostructures as smart and targeted drug delivery systems or imaging agents within living organisms. In this review, we summarize the recent advances in structure design, cargo loading and cellular delivery of DNA nanocarriers, and discuss their potential in therapeutic applications.

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FOLDNA, a Web Server for Self-Assembled DNA Nanostructure Autoscaffolds and Autostaples

Journal of Nanotechnology ◽

10.1155/2012/453953 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Chensheng Zhou ◽

Heng Luo ◽

Xiaolu Feng ◽

Xingwang Li ◽

Jie Zhu ◽

...

Keyword(s):

Drug Delivery ◽

Dna Sequences ◽

Self Assembly ◽

Web Server ◽

Automatic Design ◽

Dna Nanostructures ◽

Complementary Dna ◽

Dna Nanostructure ◽

Comprehensive Information ◽

Self Assembled

DNA self-assembly is a nanotechnology that folds DNA into desired shapes. Self-assembled DNA nanostructures, also known as origami, are increasingly valuable in nanomaterial and biosensing applications. Two ways to use DNA nanostructures in medicine are to form nanoarrays, and to work as vehicles in drug delivery. The DNA nanostructures perform well as a biomaterial in these areas because they have spatially addressable and size controllable properties. However, manually designing complementary DNA sequences for self-assembly is a technically demanding and time consuming task, which makes it advantageous for computers to do this job instead. We have developed a web server, FOLDNA, which can automatically design 2D self-assembled DNA nanostructures according to custom pictures and scaffold sequences provided by the users. It is the first web server to provide an entirely automatic design of self-assembled DNA nanostructure, and it takes merely a second to generate comprehensive information for molecular experiments including: scaffold DNA pathways, staple DNA directions, and staple DNA sequences. This program could save as much as several hours in the designing step for each DNA nanostructure. We randomly selected some shapes and corresponding outputs from our server and validated its performance in molecular experiments.

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Determinants of ligand-functionalized DNA nanostructure-cell interactions

10.1101/2021.02.24.432702 ◽

2021 ◽

Author(s):

Glenn A.O. Cremers ◽

Bas J.H.M. Rosier ◽

Ab Meijs ◽

Nicholas B. Tito ◽

Sander M.J. van Duijnhoven ◽

...

Keyword(s):

Three Dimensional ◽

Dna Nanotechnology ◽

Absolute Number ◽

Design Parameters ◽

Dna Nanostructures ◽

Surface Receptors ◽

Protein Ligands ◽

Dna Nanostructure ◽

Functionalized Nanomaterials ◽

Ligand Orientation

AbstractSynthesis of ligand-functionalized nanomaterials with control over size, shape and ligand orientation, facilitates the design of tailored nanomedicines for therapeutic purposes. DNA nanotechnology has emerged as a powerful tool to rationally construct two- and three-dimensional nanostructures, enabling site-specific incorporation of protein ligands with control over stoichiometry and orientation. To efficiently target cell surface receptors, exploration of the parameters that modulate cellular accessibility of these nanostructures is essential. In this study we systematically investigate tunable design parameters of antibody-functionalized DNA nanostructures binding to therapeutically relevant receptors. We show that, although the native affinity of antibody-functionalized DNA nanostructures remains unaltered, the absolute number of bound surface receptors is lower compared to soluble antibodies and is mainly governed by nanostructure size and DNA handle location. The obtained results provide key insights in the ability of ligand-functionalized DNA nanostructures to bind surface receptors and yields design rules for optimal cellular targeting.

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DNA nanotechnology-empowered nanoscopic imaging of biomolecules

Chemical Society Reviews ◽

10.1039/d0cs01281e ◽

2021 ◽

Author(s):

Fan Li ◽

Jiang Li ◽

Baijun Dong ◽

Fei Wang ◽

Chunhai Fan ◽

...

Keyword(s):

Dna Nanotechnology ◽

Dna Nanostructures ◽

Dna Nanostructure ◽

Imaging Probes

DNA nanotechnology has led to the rise of DNA nanostructures, which possess programmable shapes and are capable of organizing different functional molecules and materials. A variety of DNA nanostructure-based imaging probes have been developed.

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In Vitro and In Vivo Evaluation of Novel DTX-Loaded Multifunctional Heparin-Based Polymeric Micelles Targeting Folate Receptors and Endosomes

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892815666201006124604 ◽

2020 ◽

Vol 15 (4) ◽

pp. 341-359

Author(s):

Moloud Kazemi ◽

Jaber Emami ◽

Farshid Hasanzadeh ◽

Mohsen Minaiyan ◽

Mina Mirian ◽

...

Keyword(s):

Drug Delivery ◽

Antitumor Activity ◽

Cellular Uptake ◽

Folate Receptor ◽

Chemotherapeutic Agents ◽

Water Soluble ◽

Growth Monitoring ◽

Tumor Bearing

Background: The development of biocompatible tumor-targeting delivery systems for anticancer agents is essential for efficacious cancer chemotherapy. Nanoparticles, as drug delivery cargoes for cancer therapy, are rapidly improving to overcome the limitations of conventional chemotherapeutic agents. Heparin–modified nanoparticles are currently being considered as one of the favorable carriers for the delivery of chemotherapeutics to cancer tissues. Objective: This study was aimed at evaluating the in vitro and in vivo antitumor activity of a novel targeted, pH-sensitive, heparin-based polymeric micelle loaded with the poorly water-soluble anticancer drug, docetaxel (DTX). The micelles could overcome the limited water solubility, non-specific distribution, and insufficient drug concentration in tumor tissues. Methods: DTX-loaded folate targeted micelles were prepared and evaluated for physicochemical properties, drug release, in vitro cellular uptake and cytotoxicity in folate receptor-positive and folate receptor-negative cells. Furthermore, the antitumor activity of DTX-loaded micelles was evaluated in the tumor-bearing mice. Some related patents were also studied in this research. Results: The heparin-based targeted micelles exhibited higher in vitro cellular uptake and cytotoxicity against folate receptor over-expressed cells due to the specific receptor-mediated endocytosis. DTX-loaded micelles displayed greater antitumor activity, higher anti-angiogenesis effects, and lower systemic toxicity compared with free DTX in a tumor-induced mice model as confirmed by tumor growth monitoring, immunohistochemical evaluation, and body weight shift. DTX-loaded targeting micelles demonstrated no considerable toxicity on major organs of tumor-bearing mice compared with free DTX. Conclusion: Our results indicated that DTX-loaded multifunctional heparin-based micelles with desirable antitumor activity and low toxicity possess great potential as a targeted drug delivery system in the treatment of cancer.

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A DNA-binding, albumin-targeting fusion protein promotes the cellular uptake and bioavailability of framework DNA nanostructure

Nanoscale ◽

10.1039/d0nr07967g ◽

2021 ◽

Author(s):

Xue Li ◽

Fan Xu ◽

Donglei Yang ◽

Pengfei Wang

Keyword(s):

Dna Binding ◽

Fusion Protein ◽

Physicochemical Properties ◽

Cellular Uptake ◽

Dna Nanostructures ◽

Surface Functionality ◽

Dna Nanostructure

Framework DNA nanostructures exhibit unique characteristics such as precisely controllable physicochemical properties (i.e. size, shape, surface functionality) that have been used as carriers for the delivery of a variety of...

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Adenita: interactive 3D modelling and visualization of DNA nanostructures

Nucleic Acids Research ◽

10.1093/nar/gkaa593 ◽

2020 ◽

Vol 48 (15) ◽

pp. 8269-8275 ◽

Cited By ~ 3

Author(s):

Elisa de Llano ◽

Haichao Miao ◽

Yasaman Ahmadi ◽

Amanda J Wilson ◽

Morgan Beeby ◽

...

Keyword(s):

Dna Nanotechnology ◽

Software Tool ◽

Building Blocks ◽

Dna Origami ◽

Dna Nanostructures ◽

User Interactions ◽

Dna Nanostructure ◽

Dna Tiles ◽

The Creation ◽

Interactive 3D

Abstract DNA nanotechnology is a rapidly advancing field, which increasingly attracts interest in many different disciplines, such as medicine, biotechnology, physics and biocomputing. The increasing complexity of novel applications requires significant computational support for the design, modelling and analysis of DNA nanostructures. However, current in silico design tools have not been developed in view of these new applications and their requirements. Here, we present Adenita, a novel software tool for the modelling of DNA nanostructures in a user-friendly environment. A data model supporting different DNA nanostructure concepts (multilayer DNA origami, wireframe DNA origami, DNA tiles etc.) has been developed allowing the creation of new and the import of existing DNA nanostructures. In addition, the nanostructures can be modified and analysed on-the-fly using an intuitive toolset. The possibility to combine and re-use existing nanostructures as building blocks for the creation of new superstructures, the integration of alternative molecules (e.g. proteins, aptamers) during the design process, and the export option for oxDNA simulations are outstanding features of Adenita, which spearheads a new generation of DNA nanostructure modelling software. We showcase Adenita by re-using a large nanorod to create a new nanostructure through user interactions that employ different editors to modify the original nanorod.

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Choice of fluorophore affects dynamic DNA nanostructures

10.1101/2020.12.12.422444 ◽

2020 ◽

Author(s):

Kevin Jahnke ◽

Helmut Grubmüller ◽

Maxim Igaev ◽

Kerstin Göpfrich

Keyword(s):

Energy Landscape ◽

Dna Nanotechnology ◽

Reaction Diffusion ◽

Md Simulations ◽

Dna Origami ◽

Dna Nanostructures ◽

Diffusion Modeling ◽

Ph Responsive ◽

Dna Nanostructure ◽

Potential Impact

The ability to dynamically remodel DNA origami structures or functional nanodevices is highly desired in the field of DNA nanotechnology. Concomitantly, the use of fluorophores to track and validate the dynamics of such DNA-based architectures is commonplace and often unavoidable. It is therefore crucial to be aware of the side effects of popular fluorophores, which are often exchanged without considering the potential impact on the system. Here, we show that the choice of fluorophore can strongly affect the reconfiguration of DNA nanostructures. To this end, we encapsulate a triple-stranded DNA (tsDNA) into water-in-oil compartments and functionalize their periphery with a single-stranded DNA handle (ssDNA). Thus, the tsDNA can bind and unbind from the periphery by reversible opening of the triplex and subsequent strand displacement. Using a combination of experiments, molecular dynamics (MD) simulations, and reaction-diffusion modeling, we demonstrate for twelve different fluorophore combinations that it is possible to alter or even inhibit the DNA nanostructure formation - without changing the DNA sequence. Besides its immediate importance for the design of pH-responsive switches and fluorophore labelling, our work presents a strategy to precisely tune the energy landscape of dynamic DNA nanodevices.

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DNA Based and Stimuli-Responsive Smart Nanocarrier for Diagnosis and Treatment of Cancer: Applications and Challenges

Cancers ◽

10.3390/cancers13143396 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3396

Author(s):

Fakhara Sabir ◽

Mahira Zeeshan ◽

Ushna Laraib ◽

Mahmood Barani ◽

Abbas Rahdar ◽

...

Keyword(s):

Drug Delivery ◽

Rapid Development ◽

Drug Efficacy ◽

Diagnosis And Treatment ◽

Dna Nanostructures ◽

Stimuli Responsive ◽

Tumor Treatment ◽

Dna Nanostructure ◽

Treatment And Diagnosis ◽

Final Disposition

The rapid development of multidrug co-delivery and nano-medicines has made spontaneous progress in tumor treatment and diagnosis. DNA is a unique biological molecule that can be tailored and molded into various nanostructures. The addition of ligands or stimuli-responsive elements enables DNA nanostructures to mediate highly targeted drug delivery to the cancer cells. Smart DNA nanostructures, owing to their various shapes, sizes, geometry, sequences, and characteristics, have various modes of cellular internalization and final disposition. On the other hand, functionalized DNA nanocarriers have specific receptor-mediated uptake, and most of these ligand anchored nanostructures able to escape lysosomal degradation. DNA-based and stimuli responsive nano-carrier systems are the latest advancement in cancer targeting. The data exploration from various studies demonstrated that the DNA nanostructure and stimuli responsive drug delivery systems are perfect tools to overcome the problems existing in the cancer treatment including toxicity and compromised drug efficacy. In this light, the review summarized the insights about various types of DNA nanostructures and stimuli responsive nanocarrier systems applications for diagnosis and treatment of cancer.

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In vivo cloning of artificial DNA nanostructures

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0805416105 ◽

2008 ◽

Vol 105 (46) ◽

pp. 17626-17631 ◽

Cited By ~ 81

Author(s):

Chenxiang Lin ◽

Sherri Rinker ◽

Xing Wang ◽

Yan Liu ◽

Nadrian C. Seeman ◽

...

Keyword(s):

Dna Nanotechnology ◽

Dna Nanostructures ◽

Scientific Enterprise ◽

Dna Nanostructure ◽

Copy Numbers ◽

Artificial Dna ◽

Difficult Challenge ◽

Endonuclease Vii

Mimicking nature is both a key goal and a difficult challenge for the scientific enterprise. DNA, well known as the genetic-information carrier in nature, can be replicated efficiently in living cells. Today, despite the dramatic evolution of DNA nanotechnology, a versatile method that replicates artificial DNA nanostructures with complex secondary structures remains an appealing target. Previous success in replicating DNA nanostructures enzymatically in vitro suggests that a possible solution could be cloning these nanostructures by using viruses. Here, we report a system where a single-stranded DNA nanostructure (Holliday junction or paranemic cross-over DNA) is inserted into a phagemid, transformed into XL1-Blue cells and amplified in vivo in the presence of helper phages. High copy numbers of cloned nanostructures can be obtained readily by using standard molecular biology techniques. Correct replication is verified by a number of assays including nondenaturing PAGE, Ferguson analysis, endonuclease VII digestion, and hydroxyl radical autofootprinting. The simplicity, efficiency, and fidelity of nature are fully reflected in this system. UV-induced psoralen cross-linking is used to probe the secondary structure of the inserted junction in infected cells. Our data suggest the possible formation of the immobile four-arm junction in vivo.

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