scholarly journals Endogenous Stimuli-Responsive DNA Nanostructures Toward Cancer Theranostics

2020 ◽  
Vol 2 ◽  
Author(s):  
Xiaoxue Hu ◽  
Ziqi Xu ◽  
Qianhao Min ◽  
Chao Teng ◽  
Ye Tian

Nanostructures specifically responsive to endogenous biomolecules hold great potential in accurate diagnosis and precision therapy of cancers. In the pool of nanostructures with responsiveness to unique triggers, nanomaterials derived from DNA self-assembly have drawn particular attention due to their intrinsic biocompatibility and structural programmability, enabling the selective bioimaging, and site-specific drug delivery in cancer cells and tumor tissues. In this mini review, we summarize the most recent advances in the development of endogenous stimuli-responsive DNA nanostructures featured with precise self-assembly, targeted delivery, and controlled drug release for cancer theranostics. This mini review briefly discusses the diverse dynamic DNA nanostructures aiming at bioimaging and biomedicine, including DNA self-assembling materials, DNA origami structures, DNA hydrogels, etc. We then elaborate the working principles of DNA nanostructures activated by biomarkers (e.g., miRNA, mRNA, and proteins) in tumor cells and microenvironments of tumor tissue (e.g., pH, ATP, and redox gradient). Subsequently, applications of the endogenous stimuli-responsive DNA nanostructures in biological imaging probes for detecting cancer hallmarks as well as intelligent carriers for drug release in vivo are discussed. In the end, we highlight the current challenges of DNA nanotechnology and the further development of this promising research direction.

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Jaimie Marie Stewart ◽  
Elisa Franco

AbstractNucleic acid nanotechnology offers many methods to build self-assembled structures using RNA and DNA. These scaffolds are valuable in multiple applications, such as sensing, drug delivery and nanofabrication. Although RNA and DNA are similar molecules, they also have unique chemical and structural properties. RNA is generally less stable than DNA, but it folds into a variety of tertiary motifs that can be used to produce complex and functional nanostructures. Another advantage of using RNA over DNA is its ability to be encoded into genes and to be expressed in vivo. Here we review existing approaches for the self-assembly of RNA and DNA nanostructures and specifically methods to assemble large RNA structures. We describe de novo design approaches used in DNA nanotechnology that can be ported to RNA. Lastly, we discuss some of the challenges yet to be solved to build micron-scale, multi stranded RNA scaffolds.


2020 ◽  
pp. 2000291
Author(s):  
Zi‐Hao Zhou ◽  
Jian‐Guo Zhang ◽  
Qing Chen ◽  
Yan‐Ling Luo ◽  
Feng Xu ◽  
...  

2017 ◽  
Vol 97 (1) ◽  
pp. 189-225 ◽  
Author(s):  
Wujin Sun ◽  
Quanyin Hu ◽  
Wenyan Ji ◽  
Grace Wright ◽  
Zhen Gu

Physiological characteristics of diseases bring about both challenges and opportunities for targeted drug delivery. Various drug delivery platforms have been devised ranging from macro- to micro- and further into the nanoscopic scale in the past decades. Recently, the favorable physicochemical properties of nanomaterials, including long circulation, robust tissue and cell penetration attract broad interest, leading to extensive studies for therapeutic benefits. Accumulated knowledge about the physiological barriers that affect the in vivo fate of nanomedicine has led to more rational guidelines for tailoring the nanocarriers, such as size, shape, charge, and surface ligands. Meanwhile, progresses in material chemistry and molecular pharmaceutics generate a panel of physiological stimuli-responsive modules that are equipped into the formulations to prepare “smart” drug delivery systems. The capability of harnessing physiological traits of diseased tissues to control the accumulation of or drug release from nanomedicine has further improved the controlled drug release profiles with a precise manner. Successful clinical translation of a few nano-formulations has excited the collaborative efforts from the research community, pharmaceutical industry, and the public towards a promising future of smart drug delivery.


2020 ◽  
Vol 22 (1) ◽  
pp. 1-24 ◽  
Author(s):  
Dahlia Alkekhia ◽  
Paula T. Hammond ◽  
Anita Shukla

Controlled drug delivery formulations have revolutionized treatments for a range of health conditions. Over decades of innovation, layer-by-layer (LbL) self-assembly has emerged as one of the most versatile fabrication methods used to develop multifunctional controlled drug release coatings. The numerous advantages of LbL include its ability to incorporate and preserve biological activity of therapeutic agents; coat multiple substrates of all scales (e.g., nanoparticles to implants); and exhibit tuned, targeted, and/or responsive drug release behavior. The functional behavior of LbL films can be related to their physicochemical properties. In this review, we highlight recent advances in the development of LbL-engineered biomaterials for drug delivery, demonstrating their potential in the fields of cancer therapy, microbial infection prevention and treatment, and directing cellular responses. We discuss the various advantages of LbL biomaterial design for a given application as demonstrated through in vitro and in vivo studies.


2018 ◽  
Vol 14 (5) ◽  
pp. 432-439 ◽  
Author(s):  
Juliana M. Juarez ◽  
Jorgelina Cussa ◽  
Marcos B. Gomez Costa ◽  
Oscar A. Anunziata

Background: Controlled drug delivery systems can maintain the concentration of drugs in the exact sites of the body within the optimum range and below the toxicity threshold, improving therapeutic efficacy and reducing toxicity. Mesostructured Cellular Foam (MCF) material is a new promising host for drug delivery systems due to high biocompatibility, in vivo biodegradability and low toxicity. Methods: Ketorolac-Tromethamine/MCF composite was synthesized. The material synthesis and loading of ketorolac-tromethamine into MCF pores were successful as shown by XRD, FTIR, TGA, TEM and textural analyses. Results: We obtained promising results for controlled drug release using the novel MCF material. The application of these materials in KETO release is innovative, achieving an initial high release rate and then maintaining a constant rate at high times. This allows keeping drug concentration within the range of therapeutic efficacy, being highly applicable for the treatment of diseases that need a rapid response. The release of KETO/MCF was compared with other containers of KETO (KETO/SBA-15) and commercial tablets. Conclusion: The best model to fit experimental data was Ritger-Peppas equation. Other models used in this work could not properly explain the controlled drug release of this material. The predominant release of KETO from MCF was non-Fickian diffusion.


Author(s):  
Feng Wu ◽  
Fei Qiu ◽  
Siew Anthony Wai-Keong ◽  
Yong Diao

Background: In recent years, the emergence of stimuli-responsive nanoparticles makes drug delivery more efficient. As an intelligent and effective targeted delivery platform, it can reduce the side effects generated during drug transportation while enhancing the treatment efficacy. The stimuli-responsive nanoparticles can respond to different stimuli at corresponding times and locations to deliver and release their drugs and associated therapeutic effects. Objective: This review aims to inform researchers on the latest advances in the application of dual-stimuli responsive nanoparticles in precise drug delivery, with special attention to their design, drug release properties, and therapeutic effects. Syntheses of nanoparticles with simultaneous or sequential responses to two or more stimuli (pH-redox, pH-light, redoxlight, temperature-magnetic, pH-redox-temperature, redox-enzyme-light, etc.) and the applications of such responsivity properties for drugs control and release have become a hot topic of recent research. Methods: A database of relevant information for the production of this review was sourced, screened and analyzed from Pubmed, Web of Science, SciFinder by searching for the following keywords: “dual-stimuli responsive”, “controlled release”, “cancer therapy”, “synergistic treatment”. Results: Notably, the nanoparticles with dual-stimuli responsive function have an excellent control effect on drug delivery and release, playing a crucial part in the treatment of tumors. They can improve the encapsulation and delivery efficiency of hydrophobic chemotherapy drugs, combine chemo-photothermal therapies, apply imaging function in the diagnosis of tumors and even conduct multi-drugs delivery to overcome multi-drugs resistance (MDR). Conclusion: With the development of smart dual-stimuli responsive nanoparticles, cancer treatment methods will become more diverse and effective. All the stimuli-responsive nanoparticles functionalities exhibited their characteristics individually within the single nanosystem.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1502
Author(s):  
Johannes M. Parikka ◽  
Karolina Sokołowska ◽  
Nemanja Markešević ◽  
J. Jussi Toppari

The predictable nature of deoxyribonucleic acid (DNA) interactions enables assembly of DNA into almost any arbitrary shape with programmable features of nanometer precision. The recent progress of DNA nanotechnology has allowed production of an even wider gamut of possible shapes with high-yield and error-free assembly processes. Most of these structures are, however, limited in size to a nanometer scale. To overcome this limitation, a plethora of studies has been carried out to form larger structures using DNA assemblies as building blocks or tiles. Therefore, DNA tiles have become one of the most widely used building blocks for engineering large, intricate structures with nanometer precision. To create even larger assemblies with highly organized patterns, scientists have developed a variety of structural design principles and assembly methods. This review first summarizes currently available DNA tile toolboxes and the basic principles of lattice formation and hierarchical self-assembly using DNA tiles. Special emphasis is given to the forces involved in the assembly process in liquid-liquid and at solid-liquid interfaces, and how to master them to reach the optimum balance between the involved interactions for successful self-assembly. In addition, we focus on the recent approaches that have shown great potential for the controlled immobilization and positioning of DNA nanostructures on different surfaces. The ability to position DNA objects in a controllable manner on technologically relevant surfaces is one step forward towards the integration of DNA-based materials into nanoelectronic and sensor devices.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Feng Li ◽  
Wenting Yu ◽  
Jiaojiao Zhang ◽  
Yuhang Dong ◽  
Xiaohui Ding ◽  
...  

AbstractDNA nanostructures have been demonstrated as promising carriers for gene delivery. In the carrier design, spatiotemporally programmable assembly of DNA under nanoconfinement is important but has proven highly challenging due to the complexity–scalability–error of DNA. Herein, a DNA nanotechnology-based strategy via the cascade hybridization chain reaction (HCR) of DNA hairpins in polymeric nanoframework has been developed to achieve spatiotemporally programmable assembly of DNA under nanoconfinement for precise siRNA delivery. The nanoframework is prepared via precipitation polymerization with Acrydite-DNA as cross-linker. The potential energy stored in the loops of DNA hairpins can overcome the steric effect in the nanoframework, which can help initiate cascade HCR of DNA hairpins and achieve efficient siRNA loading. The designer tethering sequence between DNA and RNA guarantees a triphosadenine triggered siRNA release specifically in cellular cytoplasm. Nanoframework provides stability and ease of functionalization, which helps address the complexity–scalability–error of DNA. It is exemplified that the phenylboronate installation on nanoframework enhanced cellular uptake and smoothed the lysosomal escape. Cellular results show that the siRNA loaded nanoframework down-regulated the levels of relevant mRNA and protein. In vivo experiments show significant therapeutic efficacy of using siPLK1 loaded nanoframework to suppress tumor growth.


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