Maozhong Sun

Dual-Mode Ultrasensitive Quantification of MicroRNA in Living Cells by Chiroplasmonic Nanopyramids Self-Assembled from Gold and Upconversion Nanoparticles.

Chiral self-assembled nanomaterials with biological applications have attracted great interest. In this study, DNA-driven gold-upconversion nanoparticle (Au-UCNP) pyramids were fabricated to detect intracellular microRNA (miRNA) in real time. The Au-UCNP pyramids are doubly optically active, displaying strong plasmonic circular dichroism (CD) at 521 nm and significant luminescence in 500-600 nm, and therefore can be monitored by both of them. CD will decrease while the luminescence intensity increases in the presence of miRNA. The experimental results show that the CD intensity had an outstanding linear range from 0.073 to 43.65 fmol/10 μg(RNA) and a limit of detection (LOD) of 0.03 fmol/10 μg(RNA), whereas the luminescence intensity ranged from 0.16 to 43.65 fmol/10 μg(RNA) with a LOD of 0.12 fmol/10 μg(RNA). These data indicate that the CD signal is much more sensitive to the concentration of miRNA than the luminescent signal, which is attributed to the strong CD intensity arising from the spin angular momentum of the photon interaction with chiral nanostructures and the plasmonic enhancement of the intrinsic chirality of DNA molecules in the pyramids. This approach opens up a new avenue to the ultrasensitive detection and quantification of miRNA in living cells.

Hierarchical Plasmonic Nanorods and Upconversion Core–Satellite Nanoassemblies for Multimodal Imaging‐Guided Combination Phototherapy

DNA-driven hierarchical core-satellite nanostructures with plasmonic gold nanorod dimers and upconversion nanoparticles are fabricated. Once the core-satellite structure is activated, combined photothermal therapy and photodynamic therapy are carried out under the guidance of upconversion luminesce, T1 -weighted magnetic resonance, photoacoustics, and computed tomography imaging of tumors in vivo, which exhibit the multifunctional biological applications of the DNA-based self-assemblies.

Gold‐Quantum Dot Core–Satellite Assemblies for Lighting Up MicroRNA In Vitro and In Vivo

A high yield DNA-driven gold-quantum dot core-satellite is developed for miRNA detection in vitro and vivo. In the presence of the target miRNA, the DNA hairpin between core and satellite is ruined, resulting in the recovery of fluorescence. The limit of detection for miRNA-21 detection in living cells reaches 296 copies per cell.

Hybrid Nanoparticle Pyramids for Intracellular Dual MicroRNAs Biosensing and Bioimaging

This study strategically fabricates multifunctional nanopyramids to allow the ultrasensitive quantification of dual microRNAs (miR-203b and miR-21) in living cells and their responsive bioimaging in vivo. The nanopyramids, composed of Au-Cu9 S5 nanoparticles (NPs), upconversion NPs (UCNPs), and Ag2 S NPs, emit two luminescent signals simultaneously with excitation at 808 nm, arising from the UCNPs at 541 nm in the visible region and from the Ag2 S NPs at 1227 nm in the second window of near-infrared (NIR-II) region. The upconversion luminescence has a linear relationship with miR-203b from 0.13 to 54.54 fmol per 10 µgRNA and a limit of detection (LOD) of 0.09 fmol per 10 µgRNA , whereas the Ag2 S NP luminescence has a linear relationship with miR-21 from 0.37 to 43.56 fmol per 10 µgRNA , with a LOD of 0.23 fmol per 10 µgRNA . Significantly, this study demonstrates that the nanopyramids can be successfully used for miRs-responsive bioimaging in a tumor-bearing animal model. Furthermore, taking advantage of the photothermal capabilities of pyramids, the tumors can also be eliminated completely. These nanopyramids not only overcome the obstacles in the simultaneous detection of multiple miRs at the cellular level but also provide a cancer theranostic platform in vivo.

A Singlet Oxygen Generating Agent by Chirality-dependent Plasmonic Shell-Satellite Nanoassembly

Photodynamic therapy (PDT) agent, which generates singlet oxygen (1 O2 ) under light, has attracted significant attention for its broad biological and medical applications. Here, DNA-driven shell-satellite (SS) gold assemblies as chiral photosensitizers are first fabricated. The chiral plasmonic nanostructure, coupling with cysteine enantiomers on its surface, exhibits intense chiroplasmonic activities (-40.2 ± 2.6 mdeg) in the visible region. These chiral SS nanoassemblies have high reactive oxygen species generating efficiency under circular polarized light illumination, resulting in a 1 O2 quantum yield of 1.09. Meanwhile, it is found that SS could be utilized as PDT agent with remarkable efficiency under right circular polarized light irradiation in vitro and in vivo, allowing X-ray computed tomography (CT) and photoacoustics (PA) imaging for tumors simultaneously. The achievements reveal that the enantiomer-dependent and structure-induced nanoassemblies play an important role in PDT effects. The present researches open up a new avenue for cancer diagnose and therapy using chiral nanostructures as multifunctional platform.

A Chiral-Nanoassemblies-Enabled Strategy for Simultaneously Profiling Surface Glycoprotein and MicroRNA in Living Cells

Assemblies of nanomaterials for biological applications in living cells have attracted much attention. Herein, graphene oxide (GO)-gold nanoparticle (Au NP) assemblies are driven by a splint DNA strand, which is designed with two regions at both ends that are complementary with the DNA sequence anchored on the surface of the GO and the Au NPs. In the presence of microRNA (miR)-21 and epithelial cell-adhesion molecule (EpCAM), the hybridization of miR-21 with a molecular probe leads to the separation of 6-fluorescein-phosphoramidite-modified Au NPs from GO, resulting in a decrease in the Raman signal, while EpCAM recognition reduces circular dichroism (CD) signals. The CD signals reverse from negative in original assemblies into positive when reacted with cells, which correlates with two enantiomer geometries. The EpCAM detection has a good linear range of 8.47-74.78 pg mL-1 and a limit of detection (LOD) of 3.63 pg mL-1 , whereas miR-21 detection displays an outstanding linear range of 0.07-13.68 amol ng-1RNA and LOD of 0.03 amol ng-1RNA . All the results are in good agreement with those of the Raman and confocal bioimaging. The strategy opens up an avenue to allow the highly accurate and reliable diagnosis (dual targets) of clinic diseases.

Tuning the interactions between chiral plasmonic films and living cells

Designing chiral materials to manipulate the biological activities of cells has been an important area not only in chemistry and material science, but also in cell biology and biomedicine. Here, we introduce monolayer plasmonic chiral Au nanoparticle (NP) films modified with l- or d-penicillamine (Pen) to be developed for cell growth, differentiation, and retrieval. The monolayer films display high chiroptical activity, with circular dichroism values of 3.5 mdeg at 550 nm and 26.8 mdeg at 775 nm. The l-Pen-NP films accelerate cell proliferation, whereas the d-Pen-NP films have the opposite effect. Remote irradiation with light is chosen to noninvasively collect the cells. The results demonstrate that left circularly polarized light improves the efficiency of cell detachment up to 91.2% for l-Pen-NP films. These findings will facilitate the development of cell culture in biomedical application and help to understand natural homochirality.Chiral surfaces are emerging as important biomaterial components, as they can modulate cell behavior. Here, the authors modify plasmonic nanoparticle films with amino acid isomers, and find that the chirality of the film remarkably affects cell proliferation, adhesion, and directional differentiation.

Chirality of self-assembled metal–semiconductor nanostructures

Plasmonic nanoparticle (NP) chiral dimers are fabricated using different types of homogenous materials. However, the effect of semiconductor nanoscale dimers is unknown. This paper describes the chiroptical effect of different plasmonic metal–semiconductor hybrid nanostructures composed of gold (Au), silver (Ag) NPs and quantum dots (QDs). Three types of DNA-mediated high yield dimers were obtained, which had a distinct diverse chiroptical effect of peak position and intensity. The semiconductor QDs dimers showed a weak CD signal at 600 nm, while enhanced signals were observed after coupling with Au or Ag NPs. This interesting chiroptical effect, which originated from the assembled chiral geometry, provides a new route for further chiral structures fabrication and applications.

Site-selective photoinduced cleavage and profiling of DNA by chiral semiconductor nanoparticles

AbstractGene editing is an important genetic engineering technique that enables gene manipulation at the molecular level. It mainly relies on engineered nucleases of biological origin, whose precise functions cannot be replicated in any currently known abiotic artificial material. Here, we show that chiral cysteine-modified CdTe nanoparticles can specifically recognize and, following photonic excitation, cut at the restriction site GAT′ATC (′ indicates the cut site) in double-stranded DNA exceeding 90 base pairs, mimicking a restriction endonuclease. Although photoinduced reactive oxygen species are found to be responsible for the cleavage activity, the sequence selectivity arises from the affinity between cysteine and the conformation of the specific DNA sequence, as confirmed by quantum-chemical calculations. In addition, we demonstrate non-enzymatic sequence-specific DNA incision in living cells and in vivo using these CdTe nanoparticles, which may help in the design of abiotic materials for gene editing and other biological applications.Genome editing relies on engineered nucleases to change an organism’s DNA, but has not yet been achieved using abiotic materials. Now, chiral cysteine-capped CdTe nanoparticles are found to specifically recognize and, following photoirradiation, cut between bases T and A at the GATATC restriction site in DNA with over 90 base pairs.

Biological Molecules-Governed Plasmonic Nanoparticle Dimers with Tailored Optical Behaviors

Self-assembly opens new avenues to direct the organization of nanoparticles (NPs) into discrete structures with predefined configuration and association numbers. Plasmonic NP dimers provide a well-defined system for investigating the plasmonic coupling and electromagnetic (EM) interaction in arrays of NPs. The programmability and structural plasticity of biomolecules offers a convenient platform for constructing of NP dimers in a controllable way. Plasmonic coupling of NPs enables dimers to exhibit tunable optical properties, such as surface-enhanced Raman scattering (SERS), chirality, photoluminescence, and electrochemiluminescence (ECL) properties, which can be tailored by altering the biomolecules, the building blocks with distinct compositions, sizes and morphology, the interparticle distances, as well as the geometric configuration of the constituent NPs. An overview of recent developments in biological molecules-governed NP dimers, the tailored optical behaviors, and challenges in enhancing optical signals and proposing plasmonic biosensors are discussed in this Perspective.