DNA Nanostructures Research Articles

Interplay of graphene-DNA interactions: Unveiling sensing potential of graphene materials.

Graphene-based materials and DNA probes/nanostructures have emerged as building blocks for constructing powerful biosensors. Graphene-based materials possess exceptional properties, including two-dimensional atomically flat basal planes for biomolecule binding. DNA probes serve as excellent selective probes, exhibiting specific recognition capabilities toward diverse target analytes. Meanwhile, DNA nanostructures function as placement scaffolds, enabling the precise organization of molecular species at nanoscale and the positioning of complex biomolecular assays. The interplay of DNA probes/nanostructures and graphene-based materials has fostered the creation of intricate hybrid materials with user-defined architectures. This advancement has resulted in significant progress in developing novel biosensors for detecting DNA, RNA, small molecules, and proteins, as well as for DNA sequencing. Consequently, a profound understanding of the interactions between DNA and graphene-based materials is key to developing these biological devices. In this review, we systematically discussed the current comprehension of the interaction between DNA probes and graphene-based materials, and elucidated the latest advancements in DNA probe-graphene-based biosensors. Additionally, we concisely summarized recent research endeavors involving the deposition of DNA nanostructures on graphene-based materials and explored imminent biosensing applications by seamlessly integrating DNA nanostructures with graphene-based materials. Finally, we delineated the primary challenges and provided prospective insights into this rapidly developing field. We envision that this review will aid researchers in understanding the interactions between DNA and graphene-based materials, gaining deeper insight into the biosensing mechanisms of DNA-graphene-based biosensors, and designing novel biosensors for desired applications.

Design and Characterization of Compact, Programmable, Multistranded Nonimmunostimulatory Nucleic Acid Nanoparticles Suitable for Biomedical Applications.

We report a thorough investigation of the role of single-stranded thymidine (ssT) linkers in the stability and flexibility of minimal, multistranded DNA nanostructures. We systematically explore the impact of varying the number of ssTs in three-way junction motifs (3WJs) on their formation and properties. Through various UV melting experiments and molecular dynamics simulations, we demonstrate that while the number of ssTs minimally affects thermodynamic stability, the increasing ssT regions significantly enhance the structural flexibility of 3WJs. Utilizing this knowledge, we design triangular DNA nanoparticles with varying ssTs, all showing exceptional assembly efficiency except for the 0T triangle. All triangles demonstrate enhanced stability in blood serum and are nonimmunostimulatory and nontoxic in mammalian cell lines. The 4T 3WJ is chosen as the building block for constructing other polygons due to its enhanced flexibility and favorable physicochemical characteristics, making it a versatile choice for creating cost-effective, stable, and functional DNA nanostructures that can be stored in the dehydrated forms while retaining their structures. Our study provides valuable insights into the design and application of nucleic acid nanostructures, emphasizing the importance of understanding stability and flexibility in the realm of nucleic acid nanotechnology. Our findings suggest the intricate connection between these ssTs and the structural adaptability of DNA 3WJs, paving the way for more precise design and engineering of nucleic acid nanosystems suitable for broad biomedical applications.

Tunable Multivalent Aptamer-Based DNA Nanostructures To Regulate Multiheteroreceptor-Mediated Tumor Recognition.

Precise mapping and regulation of cell surface receptors hold immense significance in disease treatment, such as cancer, infection, and neurodisorders, but also face enormous challenges. In this study, we designed a series of adjustable multivalent aptamer-based DNA nanostructures to precisely control their interaction with receptors in tumor cells. By profiling surface receptors on 12 cell lines using 10 different aptamers, we generated a heatmap that accurately distinguished between various tumor types based on multiple markers. We then incorporated these aptamers onto DNA origami structures to regulate receptor recognition, with patch-like structures demonstrating a tendency to be trapped on the cell surface and with tube-like structures showing a preference for internalization. Through precise control of aptamer species, valence, and geometric patterns, we found that multiheteroreceptor-mediated recognition not only favored the specific binding of nanostructures to tumor cells but also greatly enhanced intracellular uptake by promoting clathrin-dependent endocytosis. Specifically, we achieved over 5-fold uptake in different tumor cells versus normal cells using tube-like structures modified with different diheteroaptamer pairs, facilitating targeted drug delivery. Moreover, patch-like structures with triheteroaptamers guided specific interactions between macrophages and tumor cells, leading to effective immune clearance. This programmable multivalent system allows for the precise regulation of cell recognition using multiple parameters, demonstrating great potential for personalized tumor treatment.

Tetrahedral DNA nanostructures enhance transcription isothermal amplification for multiplex detection of non-coding RNAs

This study introduces an innovative detection system for multiple cancer biomarkers, employing transcription isothermal amplification methods in conjunction with a tetrahedral DNA nanostructure (TDN). We demonstrate that TDN enhances various transcription isothermal amplification methods by placing DNA probes in proximity. Notably, the TDN-enhanced split T7 promoter-based isothermal transcription amplification with light-up RNA aptamer (STAR) system stands out for its optimal performance and operational simplicity, especially in identifying non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs). Multiplex detection of lncRNAs was also achieved by generating distinct light-up RNA aptamers, each emitting unique fluorescence signals. The system effectively identified the target lncRNAs, demonstrating high sensitivity and selectivity in both cell lines and clinical samples. The system, utilizing the single enzyme T7 RNA polymerase, can be easily tailored for alternative targets by substituting target-specific sequences in DNA probes and seamlessly integrated with other isothermal amplification methods for greater sensitivity and accuracy in the detection of multiple cancer biomarkers.

Self-Assembled DNA Nanospheres Driven by Carbon Dots for MicroRNAs Imaging in Tumor via Logic Circuit.

DNA nanostructures with diverse biological functions have made significant advancements in biomedical applications. However, a universal strategy for the efficient production of DNA nanostructures is still lacking. In this work, a facile and mild method is presented for self-assembling polyethylenimine-modified carbon dots (PEI-CDs) and DNA into nanospheres called CANs at room temperature. This makes CANs universally applicable to multiple biological applications involving various types of DNA. Due to the ultra-small size and strong cationic charge of PEI-CDs, CANs exhibit a dense structure with high loading capacity for encapsulated DNA while providing excellent stability by protecting DNA from enzymatic hydrolysis. Additionally, Mg2+ is incorporated into CANs to form Mg@CANs which enriches the performance of CANs and enables subsequent biological imaging applications by providing exogenous Mg2+. Especially, a DNAzyme logic gate system that contains AND and OR Mg@CANs is constructed and successfully delivered to tumor cells in vitro and in vivo. They can be specifically activated by endogenic human apurinic/apyrimidinic endonuclease 1 and recognize the expression levels of miRNA-21 and miRNA-155 at tumor sites by logic biocomputing. A versatile pattern for delivery of diverse DNA and flexible logic circuits for multiple miRNAs imaging are developed.

DNA nanostructures prevent the formation of and convert toxic amyloid proteospecies into cytocompatible and biodegradable spherical complexes

AbstractThe deposition of insoluble proteinaceous aggregates in the form of amyloid fibrils within the extracellular space of tissues is associated with numerous diseases. The development of molecular approaches to arrest amyloid formation and prevent cellular degeneration remains very challenging due to the complexity of the process of protein aggregation, which encompasses an infinite array of conformations and quaternary structures. Polyanionic biopolymers, such as glycosaminoglycans and RNAs, have been shown to modulate the self‐assembly of amyloidogenic polypeptides and to reduce the toxicity induced by the formation of oligomeric and/or pre‐fibrillar proteospecies. This study evaluates the effects of double‐stranded DNA (dsDNA) nanostructures (1D, 2D, and 3D) on amyloid self‐assembly, fibril disaggregation, and the cytotoxicity associated with amyloidogenesis. Using the islet amyloid polypeptide (IAPP) whose pancreatic accumulation is the hallmark of type 2 diabetes, it was observed that dsDNA nanostructures inhibit amyloid formation by inducing the formation of spherical complexes in which the peptide adopts a random coil conformation. Interestingly, the DNA nanostructures showed a persistent ability to disassemble enzymatically and thermodynamically stable amyloid fibrils into nanoscale DNA/IAPP entities that are fully compatible with β‐pancreatic cells and are biodegradable by proteolysis. Notably, dsDNA nanostructures avidly trapped highly toxic soluble oligomeric species in complete cell culture media and converted them into non‐toxic binary complexes. Overall, these results expose the potent modulatory effects of dsDNA on amyloidogenic pathways, and these DNA nanoscaffolds could be used as a source of inspiration for the design of molecules to fight amyloid‐related disorders.

Entropy‐Driven Strand Displacements Around DNA Tetrahedron for Sensitive Detection and Intracellular Imaging of mRNA

Messenger RNA (mRNA) is the molecule which carries genetic information from DNA and guides the synthesis of protein. It participates in many cellular cascades and exhibits substantial associations with certain diseases. The development of advanced approaches for mRNA sensing and imaging is of utmost importance for biological studies and early clinical diagnosis. Herein, a novel fluorescent method is demonstrated for highly sensitive analysis of mRNA based on entropy‐driven strand displacements around three‐dimensional DNA nanostructures. Tetrahedral DNA with four pendant linear sequences provides excellent molecular scaffold loading at multiple sites for target mRNA‐initiated cascade toehold strand displacement reactions. The variations of fluorescence resonance energy transfer states can be used to indicate the presence and level of target mRNA. Besides, MnO2 nanosheets are introduced for intracellular transportation of the reaction system for bioimaging. The operation is relatively simple and the developed approach provides a promising tool for mRNA‐related biological researches and clinical applications.

Triple multivalent aptamers within DNA tetrahedron on reduced graphene oxide electrode: Unlocking enhanced sensitivity and accelerated reactions in electrochemical sensing

DNA nanostructures are emerging as promising biosensing platforms due to their programmability, predictable assembly, and compatibility with aptamers for enhanced selectivity. This study focuses on a triple-multivalent aptamer (tApt) complex immobilized on a tetrahedral DNA nanostructure (TDN) and integrated with an electrochemically reduced graphene oxide (ERGO) electrode for highly sensitive mercury ion (Hg2+) detection. Compared to a linear multivalent aptamer-modified electrode (S2/ERGO-GCE), the 3D tApt/ERGO-GCE aptasensor exhibits superior sensitivity, signal amplification, and reaction kinetics. The tApt/ERGO-GCE sensor achieves an exceptional limit of detection (LOD) of 4.1 zM, surpassing the LOD of 0.71 fM for S2/ERGO-GCE. Additionally, the tApt/ERGO-GCE sensor demonstrates faster response times, with a half-saturation time (T1/2) of 6 minutes compared to 17 minutes for S2/ERGO/GCE. The 3D tApt aptamer's superior performance is attributed to its tetrahedral DNA structure integrated on ERGO, providing multiple aptamer binding sites, facilitating oriented immobilization on the electrode surface, and enhancing analyte capture and concentration. In contrast, the linear S2 aptamers lack rigidity, resulting in a disordered orientation on the electrode surface, hindering efficient Hg2+ binding and reducing target molecule binding efficiency. This study underscores the potential of triple-multivalent aptamer-based nanostructures for ultrasensitive and rapid biosensing applications. The tApt/ERGO-GCE aptasensor's exceptional sensitivity, signal amplification, and reaction kinetics make it a promising tool for Hg2+ detection and other biosensing applications.

An impedance labeling free electrochemical aptamer sensor based on tetrahedral DNA nanostructures for doxorubicin determination.

Based on the electrochemical impedance method, a marker-free biosensor with aptamer as a biometric element was developed for the determination of doxorubicin (DOX). By combining aptamer with rigid tetrahedral DNA nanostructures (TDNs) and fixing them on the surface of gold electrode (GE) as biometric elements, the density and directivity of surface nanoprobes improved, and DOX was captured with high sensitivity and specificity. DOX was captured by immobilized aptamers on the GE, which inhibited electron transfer between the GE and [Fe(CN)6]3-/4- in solution, resulting in a change in electrochemical impedance. When the DOX concentration was between 10.0 and 100.0nM, the aptasensor showed a linear relationship with charge transfer resistance, the relative standard deviation (RSD) ranged from 3.6 to 5.9%, and the detection limit (LOD) was 3.0nM. This technique offered a successful performance for the determination of the target analyte in serum samples with recovery in the range 97.0 to 99.6% and RSD ranged from 4.8 to 6.5%. This method displayed the advantages of fast response speed, good selectivity, and simple sensor structure and showed potential application in therapeutic drug monitoring.

Liquid DNA Coacervates form Porous Capsular Hydrogels via Viscoelastic Phase Separation on Microdroplet Interface

AbstractLiquid–liquid phase separation (LLPS) droplets of biopolymers are known as functional microdroplets in living cells and have recently been used to construct protocells and artificial cells. The formation of DNA coacervates (also referred to as DNA droplets) from branched DNA nanostructures and the control of their physical properties via DNA nanostructure design are demonstrated previously. For the construction of artificial cells or protocells, however, even though physical effects such as surface tension, wetting, and viscoelasticity are more important in a tiny (micrometer‐sized), confined environment than in a bulk solution environment, they have not been explored yet. This study shows that a tiny, confined environment using a water‐in‐oil (W/O) microdroplet interface modulates the phase separation dynamics of DNA coacervates, leading to micrometer‐sized porous capsular structures. The porous structures are produced via two types of viscoelastic phase separation (VPS) processes in DNA coacervates: i) simple VPS and ii) cluster‐cluster aggregation after VPS. Finally, it is shown that environmental chemical stimulation can manipulate porous capsular DNA hydrogels extracted from W/O microdroplets. These results provide an approach for designing and fabricating artificial cells or protocells with complex structures and physicochemical properties.

Force-induced unzipping of DNA in the presence of solvent molecules

The melting of double-stranded DNA (dsDNA) in the presence of solvent molecules is a fundamental process with significant implications for understanding the thermal and mechanical behavior of DNA and its interactions with the surrounding environment. The solvents play an essential role in the structural transformation of DNA subjected to a pulling force. In this study, we simulate the thermal and force induced denaturation of dsDNA and elucidate the solvent dependent melting behavior, identifying key factors that influence the stability of DNA melting in presence of solvent molecules. Using a statistical model, we first find the melting profile of short heterogeneous DNA molecules in the presence of solvent molecules in Force ensemble. We also investigate the effect of solvent's strengths on the melting profile of DNA. In the force ensemble, we consider two homogeneous DNA chains and apply the force on different locations along the chain in the presence of solvent molecules. Different pathways manifest the melting of the molecule in both ensembles, and we found several interesting features of melting DNA in a constant force ensemble, such as lower critical force when the chain is pulled from the base pair close to a solvent molecule. The results provide new insights into the force-induced unzipping of DNA and could be used to develop new methods for controlling the unzipping process. By providing a better understanding of melting and unzipping of dsDNA in the presence of solvent molecules, this study provides valuable guidelines for predicting DNA thermodynamic quantities and for designing DNA nanostructures.

Circular DNAzyme-Switched CRISPR/Cas12a Assay for Electrochemiluminescent Response of Demethylase Activity.

DNA nanostructure provides powerful tools for DNA demethylase activity detection, but its stability has been significantly challenged. By virtue of circular DNA with resistance to exonuclease degradation, herein, the circular DNAzyme duplex with artificial methylated modification was constructed to identify the target and output the DNA activators to drive the CRISPR/Cas12a, constructing an "on-off-on" electrochemiluminescence (ECL) biosensor for monitoring the activity of the O6-methylguanine-DNA methyltransferase (MGMT). Specifically, the circular DNAzyme duplex consisted of the chimeric RNA-DNA substrate ring with double activator sequences and two single-stranded DNAzymes, whose catalytic domains were premodified with the methyl groups. When the MGMT was present, the methylated DNAzymes were repaired and restored the catalytic activity to cleave the chimeric RNA-DNA substrates, followed by the output of DNA activators to initiate the CRISPR/Cas12a. Subsequently, the ECL signals of silver nanoparticle-modified SnO2 nanospheres (Ag@SnO2) were recovered by releasing the ferrocene-labeled quenching probes (Fc-DNA) from the electrode surface because of the trans-cleavage activity of CRISPR/Cas12a, thus achieving the specific and sensitive ECL detection of MGMT from 2.5 × 10-4 to 2.5 × 102 ng/mL with a low limit (9.69 × 10-5 ng/mL). This strategy affords novel ideas and insights into research on how to project stable nucleic acid probes to detect DNA demethylases beyond traditional methods.

DNA origami-enhanced binding of aptamers to Staphylococcus aureus cells

The combination of DNA origami nanostructures and aptamers provides a powerful technology for diagnostic assays. Here, we functionalized a DNA origami nanostructure with a Protein-A binding aptamer to target Staphylococcus aureus bacterial cells. Using an enzyme-linked oligonucleotide assay (ELONA), we semi-quantitatively analyzed and compared the interaction of the aptamer and aptamer-modified DNA origamis with Staphylococcus aureus bacterial isolates. The results showed that aptamer-functionalized DNA nanostructures bind with five times higher affinity (KD: 34 ± 5 nM) compared to the aptamer alone (KD: 160 ± 9 nM). Visualising the interaction of bacterial cells and nanostructures with electron cryotomography further confirmed the aptamer-mediated specific interaction of DNA nanostructures with bacterial cells.

Dynamic Study of Kinetically Trapped Byproducts during DNA Assembly: Case Study on a Pathway-Dependent Assembly.

Despite 40 years of development of DNA nanotechnology, the fundamental knowledge of the process of DNA strand assembly into targeted nanostructures remains unclear. Study of the dynamic process, especially the competing hybridizations in kinetic traps, provides insight into DNA assembly. In this study, a system of middle-domain first assembly (MDFA) was proposed to enable oligonucleotides to assemble into a 2D DNA monolayer in a pathway-dependent approach. This system was an ideal case to study the dynamic interactions between competing hybridizations during oligonucleotide assembly. Dynamic study revealed the coexistence of the kinetically trapped dead-end byproduct and target product at the early stage of annealing, followed by transformation of the byproduct into the target product by reverse disassembly, due to the equilibrium of the competing hybridizations increasingly favoring the target product pathway. This study offered a better understanding of the assembly pathway of DNA nanostructures for future design.

DNA framework-controlled Poly(MOFs) as a visual platform for diagnosis of HER2-positive breast cancer

The controllable assembly of metal-organic frameworks (MOFs) nanomaterials is an effective means to enhance their application capabilities. In this paper, a novel method is reported to control MOFs assembly by using a DNA framework material, a tetrahedral DNA nanostructure (TDN) labeled with phosphate groups at the vertex. In particular, various well-defined superstructures can be tailored by regulating the number of phosphate groups that coordinate with catalytic Zr-MOFs to create polymeric MOFs superstructures (Poly(MOFs)), exhibiting excellent catalytic activities and molecular recognition ability as well as greatly amplified signal readout. Furthermore, based on the DNA framework-controlled Poly(MOFs), a colorimetric biosensor with excellent analytical performance is fabricated for improving the diagnosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. It is demonstrated that the quantification of HER2 protein can be achieved at molecular level with the limit of detection (LOD) of 12 pg L-1 and cellular level with the LOD of 10 cells. More importantly, the detection of HER2 in the serum of breast cancer patients have been achieved, thus HER2-positive and triple-negative breast cancer patients can be well distinguished. Considering the substitutability of the target, this study shows great potential in biomedical research as well as clinical applications.

CRISPR/Cas systems combined with DNA nanostructures for biomedical applications.

DNA nanostructures are easy to design and construct, have good biocompatibility, and show great potential in biosensing and drug delivery. Numerous distinctive and versatile DNA nanostructures have been developed and explored for biomedical applications. In addition to DNA nanostructures that are completely assembled from DNA, composite DNA nanostructures obtained by combining DNA with other organic or inorganic materials are also widely used in related research. The CRISPR/Cas system has attracted great attention as a powerful gene editing technology and is also widely used in biomedical diagnosis. Many researchers are committed to exploring new possibilities by combining DNA nanostructures with CRISPR/Cas systems. These explorations provide support for the development of new detection methods and cargo delivery pathways, provide inspiration for improving relevant gene editing platforms, and further expand the application scope of DNA nanostructures and CRISPR/Cas systems. This paper mainly reviews the design principles and biomedical applications of CRISPR/Cas combined with DNA nanostructures based on the types of DNA nanostructures. Finally, the application status, challenges and development prospects of CRISPR/Cas combined with DNA nanostructures in detection and delivery are summarized. It is expected that this review will enable researchers to better understand the current state of the field and provide insights into the application of CRISPR/Cas systems and the development of DNA nanostructures.

Tobramycin-mediated self-assembly of DNA nanostructures for targeted treatment of Pseudomonas aeruginosa-infected lung inflammation.

Pseudomonas aeruginosa (PA) is one of the most common multidrug-resistant pathogens found in clinics, often manifesting as biofilms. However, due to the emergence of superbugs in hospitals and the overuse of antibiotics, the prevention and treatment of PA infections have become increasingly challenging. Utilizing DNA nanostructures for packaging and delivering antibiotics presents an intervention strategy with significant potential. Nevertheless, construction of functional DNA nanostructures with multiple functionalities and enhanced stability in physiological settings remains challenging. In this study, the authors propose a magnesium-free assembly method that utilizes tobramycin (Tob) as a mediator to assemble DNA nanostructures, allowing for the functionalization of DNA nanostructures by combining DNA and antibiotics. Additionally, our study incorporates maleimide-modified DNA into the nanostructures to act as a targeting moiety specifically directed towards the pili of PA. The targeting ability of the constructed functional DNA nanostructure significantly improves the local concentration of Tob, thereby reducing the side effects of antibiotics. Our results demonstrate the successful construction of a maleimide-decorated Tob/DNA nanotube (NTTob-Mal) for the treatment of PA-infected lung inflammation. The stability and biocompatibility of NTTob-Mal are confirmed, highlighting its potential for clinical applications. Furthermore, its specificity in recognizing and adhering to PA has been validated. In vitro experiments have shown its efficacy in inhibiting PA biofilm formation, and in a murine model, NTTob-Mal has exhibited significant therapeutic effectiveness against PA-induced pneumonia. In summary, the proposed antibiotic drug-mediated DNA nanostructure assembly approach holds promise as a novel strategy for targeted treatment of PA infections.

DNA nanostructures for exploring cell-cell communication.

The process of coordinating between the same or multiple types of cells to jointly execute various instructions in a controlled and carefully regulated environment is a very appealing field. In order to provide clearer insight into the role of cell-cell interactions and the cellular communication of this process in their local communities, several interdisciplinary approaches have been employed to enhance the core understanding of this phenomenon. DNA nanostructures have emerged in recent years as one of the most promising tools in exploring cell-cell communication and interactions due to their programmability and addressability. Herein, this review is dedicated to offering a new perspective on using DNA nanostructures to explore the progress of cell-cell communication. After briefly outlining the anchoring strategy of DNA nanostructures on cell membranes and the subsequent dynamic regulation of DNA nanostructures, this paper highlights the significant contribution of DNA nanostructures in monitoring cell-cell communication and regulating its interactions. Finally, we provide a quick overview of the current challenges and potential directions for the application of DNA nanostructures in cellular communication and interactions.

A DNA rotary nanodevice operated by enzyme-initiated strand resetting.

DNA nanostructures that respond to external stimuli have found applications in several areas such as biosensing, drug delivery and molecular computation. The use of different types of stimuli in a single operation provides another layer of control for the reconfiguration of nucleic acid nanostructures. This work demonstrates the use of a ribonuclease to "unset" a nucleic acid nanodevice based on the paranemic crossover (PX) DNA and specific DNA inputs to "reset" the structure into a juxtaposed DNA (JX2) configuration, resulting in a 180° rotation of the helical domains. Such operations would be useful in translational applications where DNA nanostructures can be designed to reconfigure on the basis of more than one stimulus.

Advances of fluorescent DNA nanostructures in biomedical applications

<p>With the rapid development of DNA nanotechnology, the emergence of fluorescent DNA nanostructures (FDNs) has enlarged the biological applications. FDNs have great advantages of precise localization and real-time tracing in bioimaging. In this review, the recent biomedical developments of FDNs have been reviewed, including the design of FDNs, and the corresponding applications on biomarker sensing, bioimaging, cancer diagnosis and therapy. Firstly, the development of DNA nanostructures and the corresponding DNA-based nanomaterials were briefly introduced. Simultaneously, to make a better demonstration, the background and theory of the fluorescence detections were briefly introduced. Thereafter, the synthetic strategies of DNA nanostructure were summarized and classified, which facilitated the multiple functionalizations for sensing and bioimaging. Subsequently, the biomedical applications of FDNs are comprehensively summarized based on different detection strategies, including fluorescence resonance energy transfer (FRET), nucleic acid amplification (NAT), aggregation-induced emission (AIE), near-infrared (NIR)-photoactivation, small fluorescent dyes loading, and surface plasmon resonance (SPR) technologies. Finally, an insight into the challenges and future perspectives is provided. As reviewed, FDNs are important tools in precision medicine, showing great potential in both <i>in vivo</i> and <i>in vitro</i> cancer diagnosis and treatments. Undoubtedly, FDN-based technology is a promising strategy for constructing versatile nanodevices in biological applications and will excel in human healthcare.</p>