Seeds
|
Type of DNA Templates
|
Shape of Nanomaterials
|
References
|
AuNPs/AuNRs functionalized with thiol-DNA
|
Ribbon-like DNA origami nanostructures
|
1D AuNPs/AuNRs lines or
2D AuNPs lattices
|
[54]
|
30 nm AuNPs
|
Rectangular DNA origami
|
AuNP chains
|
[47]
|
Graphdiyne and HAuCl4
|
ssDNAs (A20)
|
Decahedrons, icosahedrons, or flower-like Au nanoparticles
|
[55]
|
Gold nanorods
|
ssDNA, dsDNA, hpDNA, and taDNA
|
Trepang-like AuNCs
|
[41]
|
AuNPs and Cu
|
Bar-shaped DNA origami
|
Cu-Au metal junction
|
[56]
|
Ag Nanocube
|
10-mer oligo-A, -T, -C
|
Edge-truncated octahedral, and truncated tetrahedral AgNPs
|
[57]
|
AgNO3
|
G-/C-Rich oligonucleotides
|
Silver clusters
|
[39]
|
AgNO3
|
Triangular DNA origami template
|
Ag nanoclusters
|
[58]
|
AgNO3
|
target DNA, its complementary sequence parts, and probe DNA G4)
|
Colloidal silver solution
|
[59]
|
AgNO3
|
Telomerase primer oligonucleotides
|
Silver NPs
|
[40]
|
4. Biomedical Applications
The biomedical applications of DNA-guided metallized nanomaterials are diverse and promising, with potential applications in biosensing, bioimaging, and therapy [
70,
71].
4.1. Biosensing
DNA-guided metallized nanomaterials can also be used for biosensing applications, such as detecting biomolecules or pathogens in biological samples. By attaching DNA or antibodies to the surface of metal nanoparticles, specific interactions with target molecules can be detected using techniques such as surface plasmon resonance or electrochemistry. Chen et al. [
59] utilized Exonuclease III (Exo III) biocatalysts and silver metallization of DNA to scale up biomercaptans at picomolar concentrations. The scale-up process relies primarily on the recovery of biomercaptans, the recovery of target DNA from silver deposits, and specific interactions between the quadchain and its binding ligands. DNA-silver nanohybrids are synthesized via NaBH
4 reduction of AgNO
3. Building upon this research, Wu et al. [
40] developed a DNA metallization-based telomerase activity assay. The method utilizes a highly characteristic solid-state electrochemical process that utilizes DNA template deposition of silver nanoparticles as an electroactive label with enzyme-assisted suppression of background signals. The ion exchange process is highly selective and limited to the DNA template, significantly improving sensing performance and reducing non-specific adsorption. Furthermore, this test does not require PCR amplification, thus avoiding related errors and contamination, and enabling a more reliable evaluation of telomerase activity in circulating tumor cells (CTCs).
DNA has a high affinity for silver ions, and these local cations can be reduced to form silver nanostructures that follow the profile of the DNA template. Thus, the formation of silver nanoparticles in the DNA scaffold would block the binding of ligands embedded in DNA and may also act as a fluorescent bursting agent when some ligands are embedded in the silver-adsorbed DNA. Lin et al. [
72] first described the use of DNA-mediated silver nanostructures as a platform for simple, reliable, highly sensitive, and selective fluorescence-on detection of dopamine (DA). The method relies on large fluorescence enhancement through specific binding of the small molecule genefinder (GF) to dsDNA, which is released from the silver nanoparticles by DA. Hao et al. [
73] introduced multiple electroactive probes for the rapid detection of Cytokeratin fragment antigen 21-1 (CYFRA 21-1) DNA by surface-initiated reversible addition fragmentation chain transfer (SI-RAFT) polymerization and in situ DNA metallization as a signal amplification strategy, using C
3H
4O as a monomer. In the case of C
3H
4O as a monomer, SI-RAFT polymerization can bring a large number of aldehyde sites to the subsequent silver mirror reaction. The acrolein polymer acts as a reducing agent to reduce Ag
+ to AgO, and then silver particles are deposited on the polymer backbone, which significantly amplifies the electrochemical signal. Gong et al. [
74] used the DNA-guided growth of silver nanoclusters as a template to label catalytic and molecular beacons as an amplified biosensing platform for the detection of DNAzyme cofactors such as Pb
2+ and L-histidine. The introduction of target cofactors triggers enhanced the fluorescence of AgNCs, thus providing an “on” fluorescence response to the target biomolecule. The proposed sensing system shows a highly sensitive response to the target cofactor by cyclic amplification using multiple enzymatic conversions of the DNAzyme. Chen et al. [
75] presented the first method to implement a simple and label-free bio-thiol detection platform based on silver metallization of G-quadruplex DNA to control conformational switching. A simple, label-free, highly sensitive, and selective sensor was demonstrated for the detection of biothiols based on G-quadruplex conformational transitions designed by silver metallization. The method relies on a significant fluorescence enhancement resulting from a specific interaction between the NMM and the G-quadruplex, whose conformation is recovered after the release of the biothiols from the silver deposition.
After using dsDNA to guide copper ions for metallization, they can also be used as detection probes [
63]. Chen et al. [
64] designed a new and simple strategy for highly sensitive and selective detection of Pb
2+ using dsDNA-CuNPs as fluorescent probes. dsDNA can be used as an effective template to reduce Cu
2+ by ascorbic acid to form CuNPs, and the formed dsDNA-CuNPs have superior fluorescence. Interestingly, it was found that Pb
2+ could quench the fluorescence of dsDNA-CuNPs. Based on this phenomenon found in this work, a very simple and rapid method for Pb
2+ monitoring was established.
4.2. Bioimaging
Similarly, DNA-guided metallized nanomaterials can also be used as contrast agents in biomedical imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT). By attaching metal nanoparticles to DNA templates, contrast agents with high specificity and sensitivity can be designed for use in diagnostic imaging. Zhang et al. [
41] produced sea cucumber-like gold nanocrystals (AuNC) with tunable plasmonic properties using DNA as a template. These sea cucumber-like AuNCs exhibit a broad absorption band in the near-infrared range (700–1100 nm) and possess good thermal stability, high photothermal conversion efficiency, and biocompatibility. They were utilized for in vitro CT imaging, dark field imaging, and photothermal therapy.
Silver nanoclusters (AgNCs) prepared using DNA as a template have become an important tool for the development of biomarkers and molecular sensors because of their good fluorescence properties, excellent photostability, sub-nanometer size, and low cytotoxicity [
76,
77]. The fluorescent nature of silver nanoclusters is highly dependent on the DNA sequence and sensitive to the oligonucleotide environment, which gives them potential for genetic diagnostics. It was shown that strong base-Ag
+ binding and the formation of stable supramolecular structures such as i-motifs and G-quadruplexes are two important prerequisites for the formation of bright photoluminescent AgNC [
78]. Based on this principle, combining functional motifs of DNA (e.g., aptamers) with DNA templates for fluorescent DNA/AgNCs has been used for cell type-specific imaging. Han et al. [
79] reported the first synthesis of aptamer-AgNCs using L-DNA as a template. Compared with natural D-DNA-templated AgNCs, L-DNA-templated aptamer-AgNCs have higher nuclease resistance. This advantage makes the aptamer-AgNCs obtained by L-DNA templating more suitable for achieving cell type-specific imaging. Ran et al. [
80] used multicolor C-rich DNA template AgNCs for the first time to simultaneously image the exogenous components of the latent fingerprint (LFP) and the LFP itself. Visualization and detection of potential fingerprints are achieved by combining DNA-regulated AgNCs with molecular conjugates.
The versatility of DNA can also be exploited to combine different functional DNAs in a single structure for bioimaging. Li et al. [
81] designed a multifunctional DNA scaffold to synthesize AgNCs for intracellular imaging of tumor-associated mRNAs. The DNA scaffold contains three functional parts: SGC8c aptamer as a specific internalization part, fluorescent AgNC
S nucleating sequences, and complementary sequences (CDNAs) that can hybridize with target DNA or RNA to alter the fluorescent properties of AgNC
S. In addition, DNA-AgNCs combined with other nanomaterials can be combined to design FRET-based fluorescent probes for the fluorescent labeling of folate receptors on cancer cells [
76].
4.3. Therapy
The use of DNA-guided metallized nanomaterials in therapy has the potential to improve efficacy and specificity. By attaching drugs to the surface of metal nanoparticles guided by DNA templates, targeted drug delivery to specific tissues or cells can be achieved [
82]. Additionally, DNA-guided metallized nanomaterials can be designed to respond to specific environmental stimuli, such as changes in pH or temperature, leading to controlled drug release. In addition, the photothermal properties of metallic materials make them well-suited for photothermal therapy. Silver nanoparticles grown with DNA as a template are excellent platforms for gene delivery; DNA has a high affinity for silver ions and these local cations can be reduced to form silver nanostructures that follow the contours of the DNA template; the formation of silver nanoparticles (AgNP) in the DNA scaffold can spontaneously induce DNA bending and cohesion as well as negative charge shielding, which facilitates cellular internalization. Based on this, Tao et al. [
83] reported a simple one-pot synthesis of plasmid DNA template silver nanoparticles (pDNA-AgNPs), which can be used as a platform for efficient gene delivery. The intracellular repair of plasmid DNA (pDNA) can be achieved through a glutathione (GSH)-mediated ligand exchange process, which can facilitate efficient gene delivery. The ease of synthesis and low cytotoxicity of metallized pDNA structures compared to conventional gene carriers make them suitable biocompatible nanomaterials for biomedical applications.
The nanoparticles obtained by the metallization of DNA can be used in combination with other materials for photothermal therapy. Wang et al. [
84] combined DNA-functionalized SWCNT with DNA-guided synthesis of noble metal (Ag or Au) nanoparticles to form nanocomposites by an in situ liquid-phase synthesis method. The nanocomposites also exhibited significantly enhanced photothermal cancer cell killing due to the strong surface plasmon resonance absorption generated by the gold shells grown on the nanotube surface.
DNA-templated metallized materials can be used to act as gatekeepers for drug delivery systems. Mesoporous silica is often used to deliver drugs; however, its porous structure is prone to drug leakage. Liu et al. [
85] proposed a method to construct silver nanoparticles (AgNP) on mesoporous silica nanospheres (MSN) through a DNA templating process. The DNA strands bound to the MSN surface can form AgNP to close the pores and reduce drug leakage. Drug release is determined by specific Ag-S interactions. Subject to varying degrees of glutathione within the tumor environment, site-specific drug release can be achieved using a controlled exchange process mediated by GSH through ligand breakdown of AgNP. This interaction does not result in the formation of toxic -SH components, making it more biocompatible. Decorating MSNs with AgNPs via a DNA templating process provides a more labor-intensive yet cost-effective and robust method of nanocarrier construction, unlike traditional covalent or non-covalent strategies. This approach can also be extended to other DNA metallization nanomaterials.
Overall, these recent examples demonstrate the potential of DNA-guided metallized nanomaterials in various biomedical applications and provide a foundation for further research and development in this field.