Abstract Two‐dimensional (2D) metal organic frameworks (MOFs), are an emerging class of layered nanomaterials with well‐defined structure and modular composition. The unique pore structure, high flexibility, tunability, and ability to introduce desired functionality within the structural framework, have led to potential use of MOFs in biomedical applications. This article critically reviews the application of 2D MOFs for therapeutic delivery, tissue engineering, bioimaging, and biosensing. Further, discussion on the challenges and strategies in next generation of 2D MOFs are also included. This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
more »
« less
Functionalizing DNA nanostructures for therapeutic applications
Abstract Recent advances in nanotechnology have enabled rapid progress in many areas of biomedical research, including drug delivery, targeted therapies, imaging, and sensing. The emerging field of DNA nanotechnology, in which oligonucleotides are designed to self‐assemble into programmable 2D and 3D nanostructures, offers great promise for further advancements in biomedicine. DNA nanostructures present highly addressable and functionally diverse platforms for biological applications due to their ease of construction, controllable architecture and size/shape, and multiple avenues for chemical modification. Both supramolecular and covalent modification with small molecules and polymers have been shown to expand or enhance the functions of DNA nanostructures in biological contexts. These alterations include the addition of small molecule, protein, or nucleic acid moieties that enable structural stability under physiological conditions, more efficient cellular uptake and targeting, delivery of various molecular cargos, stimulus‐responsive behaviors, or modulation of a host immune response. Herein, various types of DNA nanostructure modifications and their functional consequences are examined, followed by a brief discussion of the future opportunities for functionalized DNA nanostructures as well as the barriers that must be overcome before their translational use. This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in BiologyTherapeutic Approaches and Drug Discovery > Emerging TechnologiesBiology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures
more »
« less
- Award ID(s):
- 1753387
- PAR ID:
- 10448419
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- WIREs Nanomedicine and Nanobiotechnology
- Volume:
- 13
- Issue:
- 6
- ISSN:
- 1939-5116
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Watson–Crick base pairing rules provide a powerful approach for engineering DNA‐based nanodevices with programmable and predictable behaviors. In particular, DNA strand displacement reactions have enabled the development of an impressive repertoire of molecular devices with complex functionalities. By relying on DNA to function, dynamic strand displacement devices represent powerful tools for the interrogation and manipulation of biological systems. Yet, implementation in living systems has been a slow process due to several persistent challenges, including nuclease degradation. To circumvent these issues, researchers are increasingly turning to chemically modified nucleotides as a means to increase device performance and reliability within harsh biological environments. In this review, we summarize recent progress toward the integration of chemically modified nucleotides with DNA strand displacement reactions, highlighting key successes in the development of robust systems and devices that operate in living cells and in vivo. We discuss the advantages and disadvantages of commonly employed modifications as they pertain to DNA strand displacement, as well as considerations that must be taken into account when applying modified oligonucleotide to living cells. Finally, we explore how chemically modified nucleotides fit into the broader goal of bringing dynamic DNA nanotechnology into the cell, and the challenges that remain. This article is categorized under:Diagnostic Tools > In Vivo Nanodiagnostics and ImagingNanotechnology Approaches to Biology > Nanoscale Systems in BiologyDiagnostic Tools > Biosensingmore » « less
-
Abstract While plasma concentration kinetics has traditionally been the predictor of drug pharmacological effects, it can occasionally fail to represent kinetics at the site of action, particularly for solid tumors. This is especially true in the case of delivery of therapeutic macromolecules (drug‐loaded nanomaterials or monoclonal antibodies), which can experience challenges to effective delivery due to particle size‐dependent diffusion barriers at the target site. As a result, disparity between therapeutic plasma kinetics and kinetics at the site of action may exist, highlighting the importance of target site concentration kinetics in determining the pharmacodynamic effects of macromolecular therapeutic agents. Assessment of concentration kinetics at the target site has been facilitated by non‐invasive in vivo imaging modalities. This allows for visualization and quantification of the whole‐body disposition behavior of therapeutics that is essential for a comprehensive understanding of their pharmacokinetics and pharmacodynamics. Quantitative non‐invasive imaging can also help guide the development and parameterization of mathematical models for descriptive and predictive purposes. Here, we present a review of the application of state‐of‐the‐art imaging modalities for quantitative pharmacological evaluation of therapeutic nanoparticles and monoclonal antibodies, with a focus on their integration with mathematical models, and identify challenges and opportunities. This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseDiagnostic Tools > in vivo Nanodiagnostics and ImagingNanotechnology Approaches to Biology > Nanoscale Systems in Biologymore » « less
-
Abstract Gaseous signaling molecules such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) have recently been recognized as essential signal mediators that regulate diverse physiological and pathological processes in the human body. With the evolution of gaseous signaling molecule biology, their therapeutic applications have attracted growing attention. One of the challenges in translational research of gaseous signaling molecules is the lack of efficient and safe delivery systems. To tackle this issue, researchers developed a library of gas donors, which are low molecular weight compounds that can release gaseous signaling molecules upon decomposition under physiological conditions. Despite the significant efforts to control gaseous signaling molecule release from gas donors, the therapeutic potential of gaseous signaling molecules cannot be fully explored due to their unfavorable pharmacokinetics and toxic side effects. Recently, the use of nanoparticle‐based gas donors, especially self‐assembled polymeric gas donors, have emerged as a promising approach. In this review, we describe the development of conventional small gas donors and the challenges in their therapeutic applications. We then illustrate the concepts and critical aspects for designing self‐assembled polymeric gas donors and discuss the advantages of this approach in gasotransmistter delivery. We also highlight recent efforts to develop the delivery systems for those molecules based on self‐assembled polymeric nanostructures. This article is categorized under:Therapeutic Approaches and Drug Discovery > Emerging Technologiesmore » « less
-
DNA nanotechnology has proven exceptionally apt at probing and manipulating biological environments as it can create nanostructures of almost arbitrary shape that permit countless types of modifications, all while being inherently biocompatible. Emergent areas of particular interest are applications involving cellular membranes, but to fully explore the range of possibilities requires interdisciplinary knowledge of DNA nanotechnology, cell and membrane biology, and biophysics. In this review, we aim for a concise introduction to the intersection of these three fields. After briefly revisiting DNA nanotechnology, as well as the biological and mechanical properties of lipid bilayers and cellular membranes, we summarize strategies to mediate interactions between membranes and DNA nanostructures, with a focus on programmed delivery onto, into, and through lipid membranes. We also highlight emerging applications, including membrane sculpting, multicell self-assembly, spatial arrangement and organization of ligands and proteins, biomechanical sensing, synthetic DNA nanopores, biological imaging, and biomelecular sensing. Many critical but exciting challenges lie ahead, and we outline what strikes us as promising directions when translating DNA nanostructures for future in vitro and in vivo membrane applications.more » « less