Strategies for functionalizing diverse tetrahedral framework nucleic acids (tFNAs) have been extensively explored since the first successful fabrication of tFNA by Turberfield. One-pot annealing of at least four DNA single strands is the most common method to prepare tFNA, as it optimizes the cost, yield, and speed of assembly. This review concentrates on four key merits of tFNAs and their potential for biomedical applications. The natural ability of tFNA to scavenge reactive oxygen species, along with remarkable enhancement in cellular endocytosis and tissue permeability based on its appropriate size and geometry, promotes cell-material interaction to direct or probe cell behavior, especially to treat inflammatory and degenerative diseases. Moreover, the structural programmability of tFNA enables the development of static tFNA-based nanomaterials via engineering of functional oligonucleotides or therapeutic molecules, and dynamic tFNAs via attachment of stimuli-responsive DNA apparatuses, leading to potentially applications in targeted therapies, tissue regeneration, antitumor strategies, and antibacterial treatment. Although there are impressive performance and significant progress, challenges and prospects of functionalizing tFNA-based nanostructures are still indicated in this review. This article is protected by copyright. All rights reserved 

Functionalizing Framework Nucleic‐Acid‐Based Nanostructures for Biomedical Application

In recent years, an increasing number of nanomaterials have been explored for their applications in biomedical diagnostics, making their applications in healthcare biosensing a rapidly evolving field. Nanomaterials introduce versatility to the sensing platforms and may even allow mobility between different detection mechanisms. The prospect of a combination of different nanomaterials allows an exploitation of their synergistic additive and novel properties for sensor development. This paper covers more than 290 research works since 2015, elaborating the diverse roles played by various nanomaterials in the biosensing field. Hence, we provide a comprehensive review of the healthcare sensing applications of nanomaterials, covering carbon allotrope-based, inorganic, and organic nanomaterials. These sensing systems are able to detect a wide variety of clinically relevant molecules, like nucleic acids, viruses, bacteria, cancer antigens, pharmaceuticals and narcotic drugs, toxins, contaminants, as well as entire cells in various sensing media, ranging from buffers to more complex environments such as urine, blood or sputum. Thus, the latest advancements reviewed in this paper hold tremendous potential for the application of nanomaterials in the early screening of diseases and point-of-care testing.

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Nanomaterials for Healthcare Biosensing Applications

Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are natural biopolymers composed of nucleotides that store, transmit, and express genetic information. Overexpressed or underexpressed as well as mutated nucleic acids have been implicated in many diseases. Therefore, nucleic acid tests (NATs) are extremely important. Inspired by intracellular DNA replication and RNA transcription, in vitro NATs have been extensively developed to improve the detection specificity, sensitivity, and simplicity. The principles of NATs can be in general classified into three categories: nucleic acid hybridization, thermal-cycle or isothermal amplification, and signal amplification. Driven by pressing needs in clinical diagnosis and prevention of infectious diseases, NATs have evolved to be a rapidly advancing field. During the past ten years, an explosive increase of research interest in both basic research and clinical translation has been witnessed. In this review, we aim to provide comprehensive coverage of the progress to analyze nucleic acids, use nucleic acids as recognition probes, construct detection devices based on nucleic acids, and utilize nucleic acids in clinical diagnosis and other important fields. We also discuss the new frontiers in the field and the challenges to be addressed.

Nucleic Acid Tests for Clinical Translation.

Cell plasma membrane, the boundary between an individual live cell and its microenvironment, plays important roles in cellular communication and signaling, and associates with many physiological and pathological processes. For better understanding the membrane-related biological processes, a number of fluorescent probes have been developed in the past few years. According to their different functions and targeting mechanisms, we herein provide an overview of the advances in the development of fluorescent probes for cell plasma membrane biology and biophysics research. Fluorescent probes specific for cell plasma membrane labelling are initially discussed based on their different targeting mechanisms, which is followed by the summary of membrane-targeting responsive fluorescence probes for various biomolecules detection. Challenges and future research directions for the development of new generation fluorescent probes for cell plasma membrane dynamics investigations are outlined in the end.

Advances in the development of fluorescence probes for cell plasma membrane imaging

Label-free probes using DNA-templated silver nanoclusters as versatile reporters.

Three-dimensional DNA nanostructures for dual-color microRNA imaging in living cells via hybridization chain reaction.

Homogeneous label-free protein binding assay using small-molecule-labeled DNA nanomachine with DNAzyme-Based chemiluminescence detection

Small molecule-linked programmable DNA for washing-free imaging of cell surface biomarkers

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Three-dimensional DNA nanostructures for dual-color microRNA imaging in living cells via hybridization chain reaction.

Homogeneous label-free protein binding assay using small-molecule-labeled DNA nanomachine with DNAzyme-Based chemiluminescence detection

Small molecule-linked programmable DNA for washing-free imaging of cell surface biomarkers