Symmetry-Breaking of Nanoparticle Surface Function Via Conformal DNA Design.

Asymmetric surface functionalization of complex nanoparticles to control their directional self-assembly remains a considerable challenge. Here, we demonstrated a conformal DNA design strategy for flexible remodeling of the surface of complex nanoparticles, taking Au nanobipyramids (AuNBPs) as a model. We sheathed one or both tips of AuNBPs into conformal DNA origami with an exceptionally accurate orientation control. Such asymmetrically and symmetrically distributed surface patches possess regioselective, sequence, and site-specific DNA binding capabilities. As a result, we realized a series of prototypical multicomponent "colloidal molecules" made of AuNBPs and Au nanospheres (AuNSs) with defined directionality and number of "bonding valence" as well as 1D and 3D hierarchical assemblies, e.g., inverse core-satellites of AuNBPs and AuNSs, side-by-side and tip-to-tip linear assemblies of AuNBPs, and 3D helical superstructures of AuNBPs with tunable twists. These findings inspire new opportunities for nanoparticle surface engineering and the high-order self-assembly of nanoarchitectures with higher complexity and broadened functionalities.

Designable Nanoadaptor for Enhanced Recognition of Natural Killer Cell to Tumor via Bio-orthogonal Click Reaction.

Highly efficient recognition of cancer cells by immune cells is important for successful therapeutic-cell-based cancer immunotherapy. Herein, we present a facile NIR-II nanoadaptor [hyaluronic acid (HA)/dibenzocyclooctyne (DBCO)-Au:Ag2Te quantum dots (QDs)] for enhancing the tumor recognition and binding ability of natural killer (NK) cells via a bio-orthogonal click reaction in vivo. The Nanoadaptor possesses superior tumor-targeting capacity, facilitating the accumulation of the chemical receptor DBCO at the tumor sites. Subsequently, the enrichment of DBCO on tumor cell surfaces provides multivalent recognition sites for capturing pretreated azide engineered NK92 cells (NK92-N3) through an efficient click reaction, thereby significantly enhancing the therapeutical efficiency. The dynamic process of nanoadaptor-mediated recognition of NK cells to tumor cells could be vividly observed using multiplexed NIR-II fluorescence imaging in a mouse model of lung cancer. Such a nanoadaptor strategy can be extended to other therapeutic cellular systems and holds promise for future clinical applications.

Programmed Remodeling of the Tumor Milieu to Enhance NK Cell Immunotherapy Combined with Chemotherapy for Pancreatic Cancer.

Natural killer (NK) cell-based adoptive immunotherapy has demonstrated encouraging therapeutic effects in clinical trials for hematological cancers. However, the effectiveness of treatment for solid tumors remains a challenge due to insufficient recruitment and infiltration of NK cells into tumor tissues. Herein, a programmed nanoremodeler (DAS@P/H/pp) is designed to remodel dense physical stromal barriers and for dysregulation of the chemokine of the tumor environment to enhance the recruitment and infiltration of NK cells in tumors. The DAS@P/H/pp is triggered by the acidic tumor environment, resulting in charge reversal and subsequent hyaluronidase (HAase) release. HAase effectively degrades the extracellular matrix, promoting the delivery of immunoregulatory molecules and chemotherapy drugs into deep tumor tissues. In mouse models of pancreatic cancer, this nanomediated strategy for the programmed remodeling of the tumor microenvironment significantly boosts the recruitment of NK92 cells and their tumor cell-killing capabilities under the supervision of multiplexed near-infrared-II fluorescence.

Tailoring Near-Infrared-IIb Fluorescence of Thulium(III) by Nanocrystal Structure Engineering.

Currently, mainstream lanthanide probes with fluorescence located in the second near-infrared subwindow of 1500-1700 nm (NIR-IIb) are predominantly Er(III)-based nanoparticles (NPs). Here we report a newly developed NIR-IIb fluorescent nanoprobe, α-Tm NP (cubic-phase NaYF4@NaYF4:Tm@NaYF4), with an emission at 1630 nm. We activate the 1630 nm emission of Tm(III) in α-Tm NP through the large spread of the Stark split sublevels induced by the crystal-field effect of the α-NaYF4 host. Further, we systematically investigated the effect of crystalline structure of the host NaYF4 NP (cubic phase (α) or hexagonal phase (ß)), the type and concentrations of dopants (Yb(III), Tm(III), and Ca(II) ions) in the α-phase host, and the thicknesses of the interlayer and inert shell on the NIR-IIb fluorescence of Tm(III). The ultimate nanostructure presents a significant enhancement factor of the NIR-IIb photoluminescence intensity of Tm(III) up to ∼315. With this bright NIR-IIb fluorescent nanoprobe, we demonstrate high-spatial-resolution time-coursing imaging of breast cancer bone metastasis.

Interface-Mediation-Enabled High-Performance Near-Infrared AgAuSe Quantum Dot Light-Emitting Diodes.

Near-infrared (NIR) quantum dot (QD) light-emitting diodes (LEDs) (NIR-QLEDs) for recognition and tracking applications underpin the future of night-vision technology. However, the performance of environmentally benign materials and devices has lagged far behind that of their Pb-containing counterparts. In this study, we demonstrate the superior performance of NIR-QLEDs based on efficient AgAuSe QDs with contact interface mediation. Consequently, we reveal that using cysteamine-treated QD film contact heterointerfaces can effectively eliminate contact defects in devices and preserve their excellent emissive properties. Additionally, the dipole moment orientation of the coordinated additives is inverse of the heterojunction potential difference, simultaneously blocking electrons and enhancing hole injection in operando, optimizing the LED charge injection balance. These devices exhibit a high external quantum efficiency (EQE) and a power conversion efficiency (PCE) of 15.8 and 12.7% at 1046 nm, respectively, a sub-band gap turn-on voltage of 0.9 V, and a low current density (over 10% of the EQE from 0.0017 to 0.31 mA cm-2). These are the highest EQE and PCE values ever reported for environmentally benign NIR-QLEDs. The results of this study can provide a general strategy for the practical application of QDs in electroluminescent devices.

Planar oligomerization of reconfigurable gold nanorod dimers.

Reconfigurable chiral plasmonic complexes are fabricated by planar assembly of multiple individual gold nanorod dimers using DNA origami templates. Additionally, each chiral center can be controlled to switch among achiral, left-handed, and right-handed states. We demonstrate that their overall circular dichroism is determined by the coupling of individual chiral centers and is heavily influenced by the precise number and arrangement of these centers. Our study offers a novel self-assembly method for constructing intricate and dynamic chiral plasmonics as well as investigating the interactions among several plasmonic chiral centers.

Unveiling the energy transfer mechanism between aqueous colloidal NIR-II quantum dots and water.

Hydrophilic semiconductor quantum dots (QDs) with emission in the second near-infrared window (NIR-II) have been widely studied in bioimaging applications. In such cases, QDs are usually dispersed in water. As is known, water has strong absorbance in the NIR-II region. However, investigations on the interaction between NIR-II emitters and water molecules are ignored in previous studies. Herein, we synthesized a series of mercaptoundecanoic acid-coated silver sulfide (Ag2S/MUA) QDs with various emissions that partially or completely overlapped with the absorbance of water at 1200 nm. By constructing a hydrophobic interface of cetyltrimethylammonium bromide (CTAB) with MUA on the Ag2S QDs surface via forming an ionic bond, significant enhancement of Ag2S QDs photoluminescence (PL) intensity was observed, as well as a prolonged lifetime. These findings suggest that there is an energy transfer between Ag2S QDs and water in addition to the classical resonance absorption. Transient absorption and fluorescence spectra results revealed that the increased PL intensities and lifetime of Ag2S QDs originated from the suppressed energy transfer from Ag2S QDs to the water due to the CTAB bridged hydrophobic interfaces. This discovery is important for a deeper understanding of the photophysical mechanisms of QDs and their applications.

Noncovalent Self-Assembly of Protein Crystals with Tunable Structures.

Engineering noncovalent interactions for assembling nonspherical proteins into supramolecular architectures with tunable morphologies and dynamics is challenging due to the structural heterogeneity and complexity of protein surfaces. Herein, we employed an anisotropic building block l-rhamnulose-1-phosphate aldolase (RhuA) to control supramolecular polymorphism in highly ordered protein assemblies by introducing histidine residues. Histidine-based π-π stacking interactions enabled thermodynamically controlled self-organization of RhuA to form three-dimensional (3D) nanoribbons and crystals. Self-assembly of different 3D crystal phases was kinetically modulated by the strong metal ion-histidine chelation, and double-helical protein superstructures were formed by engineering increased histidine interactions at the RhuA binding surface. Their structural properties and dynamics were determined via fluorescence microscopy, transmission electron microscopy, atomic force microscopy, and small-angle X-ray scattering. This work is aimed at expanding the toolbox for the programming of tunable, highly ordered, protein superstructures and increasing the understanding of the mechanisms of protein interfacial interactions.

Activatable Rare Earth Near-Infrared-II Fluorescence Ratiometric Nanoprobes.

Rational design of efficient lanthanide-doped down-shifting nanoparticles (DSNPs) has attracted tremendous attention. However, energy loss was inevitable in the multiple Ln3+ doping systems owing to complex energy migration processes. Here, an efficient NaErF4@NaYF4@NaYF4:10%Nd@NaYF4 DSNP was tactfully designed, in which a buffer layer of NaYF4 was modulated to restrict the interionic energy migration between Er3+ and Nd3+; meanwhile, the surface defects were passivated by an outermost layer of NaYF4. Therefore, the as-prepared DSNPs exhibited two intensive near-infrared-II fluorescence emissions of 1525 nm from Er3+ and 1060 nm from doped Nd3+ under 808 nm excitation. Further, a novel ratiometric nanoprobe NaErF4@NaYF4@NaYF4:10%Nd@NaYF4@A1094 was fabricated by coupling an organic dye of A1094 onto the DSNP surface to quench the 1060 nm emission by the efficient Förster resonance energy transfer, while emission at 1525 nm retained. Thereafter, these activatable ratiometric nanoprobes were used for rapid and sensitive detection of peroxynitrite (ONOO-) in vivo.

Finite Assembly of Three-Dimensional DNA Hierarchical Nanoarchitectures through Orthogonal and Directional Bonding.

Reliable orthogonal bonding with precise and flexible orientation control would be ideal for building finite complex nanostructures via self-assembly. Employing a three-dimensional (3D) DNA origami, hexagonal prism DNA origami (HDO), as building block, we demonstrate it is practical to construct finite hierarchical nanoarchitectures with complicated conformations through orthogonal and directional bonding. The as-designed HDO building block has twelve prescribed directional valences in 3D space and each of them supports two opposite orientations, yielding the capability to generate abundant directional bonding. Meanwhile, we minimize the thorny non-specific interactions among HDOs and enable the orthogonal bonding between any two valences based on self-similar designing. Consequently, various hierarchical nanostructures are prepared at will simply by the combination of HDOs with appropriate valences. We believe this route towards hierarchically assembly is inspiring and hope it will facilitate the fabrication of functional superstructures.

Colloidal Alloyed Quantum Dots with Enhanced Photoluminescence Quantum Yield in the NIR-II Window.

Semiconductor quantum dots (QDs) with photoluminescence (PL) emission at 900-1700 nm (denoted as the second near-infrared window, NIR-II) exhibit much-depressed photon absorption and scattering, which has stimulated extensive researches in biomedical imaging and NIR devices. However, it is very challenging to develop NIR-II QDs with a high photoluminescence quantum yield (PLQY) and excellent biocompatibility. Herein, we designed and synthesized an alloyed silver gold selenide (AgAuSe) QD with a bright emission from 820 to 1170 nm and achieved a record absolute PLQY of 65.3% at 978 nm emission among NIR-II QDs without a toxic element and a long lifetime of 4.58 µs. It is proved that the high PLQY and long lifetime are mainly attributed to the prevented nonradiative transition of excitons, probably resulted from suppressing cation vacancies and crystal defects from the high mobility of Ag ions by alloying Au atoms. These high-PLQY QDs with nontoxic heavy metal exhibit great application potential in bioimaging, light emitting diodes (LEDs), and photovoltaic devices.

Pb-Doped Ag2 Se Quantum Dots with Enhanced Photoluminescence in the NIR-II Window.

Ag2 Se quantum dots (QDs) as an effective biological probe in the second near-infrared window (NIR-II, 1000-1700 nm) have been widely applied in bioimaging with high tissue penetration depth and high spatiotemporal resolution. However, the ions deficiency and crystal defects caused by the high Ag+ mobility in Ag2 Se crystals are mainly responsible for the inefficient photoluminescence (PL) of Ag2 Se QDs. Herein, a tailored route is reported to achieve controllable doping of Ag2 Se QDs in which Ag is exchanged by Pb via cation exchange (CE), which is unattainable by direct synthetic methods. The Pb-doped Ag2 Se QDs (denoted as Pb:Ag2 Se QDs) present fire-new optical features with significantly enhanced PL intensity of 4.2 folds. Photoelectron spectroscopy confirms that Pb acts as an n-type dopant for Ag2 Se QDs and therefore the electronic impurities provide additional carriers to fill the traps. Moreover, the general validity of this method is demonstrated to convert different sized Ag2 Se into Pb:Ag2 Se QDs, so that a wide range of NIR-II PL with high intensity is obtained. The bright NIR-II emission of Pb:Ag2 Se QDs is further successfully performed in lymphatic system mapping.

Whole-Body Fluorescence Imaging in the Near-Infrared Window.

Fluorescence imaging is one of the most widely used in vivo imaging methods for both fundamental research and clinical practice. Due to the reduced photon scattering, absorption, and autofluorescence in tissues, the emerging near-infrared (NIR) imaging (650-1700 nm) can afford deep tissue imaging with high spatiotemporal resolution and in vivo report the anatomical structures as well as the physiological activities in a whole-body level. Here, we give a brief introduction to fluorescence imaging in the first NIR (NIR-I, 650-950 nm) and second NIR (NIR-II, 1000-1700 nm) windows, summarize the recently developed NIR fluorophores and their applications in whole-body vascular system imaging, precision cancer theranostics, and regenerative medicine. Finally, the clinical applications and future prospects of in vivo NIR fluorescence imaging are also discussed.

Precise Fabrication of De Novo Nanoparticle Lattices on Dynamic 2D Protein Crystalline Lattices.

The science of protein self-assembly has experienced significant development, from discrete building blocks of self-assembled nanoarchitectures to advanced nanostructures with adaptive functionalities. Despite the prominent achievements in the field, the desire of designing de novo protein-nanoparticle (NP) complexes and constructing dynamic NP systems remains highly challenging. In previous works, l-rhamnulose-1-phosphate aldolase (C98RhuA) tetramers were self-assembled into two-dimensional (2D) lattices via disulfide bond interactions. These interactions provided 2D lattices with high structural quality and a sophisticated assembly mode. In this study, we devised a rational design for RhuA building blocks to fabricate 2D functionalized protein lattices. More importantly, the lattices were used to direct the precise assembly of NPs into highly ordered and diverse nanoarchitectures. These structures can be employed as an excellent tool to adequately verify the self-assembly mode and structural quality of the designed RhuA crystals. The subsequent redesign of RhuA building blocks enabled us to predictably produce a novel protein lattice whose conformational dynamics can be controllably regulated. Thus, a dynamic system of AuNP lattices was achieved. Transmission electron microscopy and small-angle X-ray scattering indicated the presence of these diverse NP lattices. This contribution enables the fabrication of future NP structures in a more programmable manner with more expected properties for potential applications in nanoelectronics and other fields.

Rapid Unperturbed-Tissue Analysis for Intraoperative Cancer Diagnosis Using an Enzyme-Activated NIR-II Nanoprobe.

Accurate intraoperative tissue identification is critical to tumor surgery. However, conventional methods are labor- and time-intensive, which greatly delay the intraoperative decision-making. Herein, a matrix metalloproteinase (MMP)14-activated NIR-II nanoprobe (A&MMP@Ag2 S-AF7P) is presented for rapid unperturbed-tissue analysis for ex vivo and in vivo neuroblastoma diagnosis. A&MMP@Ag2 S-AF7P displays negligible fluorescence in normal tissues but is activated quickly by inhibiting the fluorescence resonance energy transfer (FRET) between Ag2 S QDs and A1094 mediated by MMP14 overexpressed in neuroblastoma; meanwhile, the exposure of the membrane penetrating peptide R9 (TAT-peptide) results in efficient internalization of nanoprobes in the cancer cells, providing superior tumor-to-normal (T/N) tissue ratio. Instant illumination of the lesion and well-defined tumor margins make the nanoprobes a suitable rapid diagnostic reagent for cancer surgical or tissue biopsy procedures.

Advanced Fluorescence Imaging Technology in the Near-Infrared-II Window for Biomedical Applications.

Fluorescence imaging has become a fundamental tool for biomedical applications; nevertheless, its intravital imaging capacity in the conventional wavelength range (400-950 nm) has been restricted by its extremely limited tissue penetration. To tackle this challenge, a novel imaging approach using the fluorescence in the second near-infrared window (NIR-II, 1000-1700 nm) has been developed in the past decade to achieve deep penetration and high-fidelity imaging, and thus significant biomedical applications have begun to emerge. In this Perspective, we first examine recent discoveries and challenges in the development of novel NIR-II fluorophores and compatible imaging apparatuses. Subsequently, the recent advances in bioimaging, biosensing, and therapy using such a cutting-edge imaging technique are highlighted. Finally, based on the achievement in the representative studies, we elucidate the main concerns regarding this imaging technique and give some advice and prospects for the development of NIR-II imaging for future biomedical applications.

Programming Dynamic Assembly of Viral Proteins with DNA Origami.

Biomolecular assembly in biological systems is typically a complex dynamic process regulated by the exchange of molecular information between biomolecules such as proteins and nucleic acids. Here, we demonstrate a nucleic-acid-based system that can program the dynamic assembly process of viral proteins. Tobacco mosaic virus (TMV) genome-mimicking RNA is anchored on DNA origami nanostructures via hybridization with a series of DNA strands which also function as locks that prevent the packaging of RNA by the TMV proteins. The selective, sequential releasing of the RNA via toehold-mediated strand displacement allows us to program the availability of RNA and subsequently the TMV growth in situ. Furthermore, the programmable dynamic assembly of TMV on DNA templates also enables the production of new DNA-protein hybrid nanostructures, which are not attainable by using previous assembly methods.

Controlled Synthesis of Ag2 Te@Ag2 S Core-Shell Quantum Dots with Enhanced and Tunable Fluorescence in the Second Near-Infrared Window.

Fluorescence in the second near-infrared window (NIR-II, 900-1700 nm) has drawn great interest for bioimaging, owing to its high tissue penetration depth and high spatiotemporal resolution. NIR-II fluorophores with high photoluminescence quantum yield (PLQY) and stability along with high biocompatibility are urgently pursued. In this work, a Ag-rich Ag2 Te quantum dots (QDs) surface with sulfur source is successfully engineered to prepare a larger bandgap of Ag2 S shell to passivate the Ag2 Te core via a facile colloidal route, which greatly enhances the PLQY of Ag2 Te QDs and significantly improves the stability of Ag2 Te QDs. This strategy works well with different sized core Ag2 Te QDs so that the NIR-II PL can be tuned in a wide range. In vivo imaging using the as-prepared Ag2 Te@Ag2 S QDs presents much higher spatial resolution images of organs and vascular structures as compared with the same dose of Ag2 Te nanoprobes administrated, suggesting the success of the core-shell synthetic strategy and the potential biomedical applications of core-shell NIR-II nanoprobes.

Chiral Plasmonic Nanostructures Enabled by Bottom-Up Approaches.

We present a comprehensive review of recent developments in the field of chiral plasmonics. Significant advances have been made recently in understanding the working principles of chiral plasmonic structures. With advances in micro- and nanofabrication techniques, a variety of chiral plasmonic nanostructures have been experimentally realized; these tailored chiroptical properties vastly outperform those of their molecular counterparts. We focus on chiral plasmonic nanostructures created using bottom-up approaches, which not only allow for rational design and fabrication but most intriguingly in many cases also enable dynamic manipulation and tuning of chiroptical responses. We first discuss plasmon-induced chirality, resulting from the interaction of chiral molecules with plasmonic excitations. Subsequently, we discuss intrinsically chiral colloids, which give rise to optical chirality owing to their chiral shapes. Finally, we discuss plasmonic chirality, achieved by arranging achiral plasmonic particles into handed configurations on static or active templates. Chiral plasmonic nanostructures are very promising candidates for real-life applications owing to their significantly larger optical chirality than natural molecules. In addition, chiral plasmonic nanostructures offer engineerable and dynamic chiroptical responses, which are formidable to achieve in molecular systems. We thus anticipate that the field of chiral plasmonics will attract further widespread attention in applications ranging from enantioselective analysis to chiral sensing, structural determination, and in situ ultrasensitive detection of multiple disease biomarkers, as well as optical monitoring of transmembrane transport and intracellular metabolism.

Interfacially Bridging Covalent Network Yields Hyperstable and Ultralong Virus-Based Fibers for Engineering Functional Materials.

We present a strategy of interfacially bridging covalent network within tobacco mosaic virus (TMV) virus-like particles (VLPs). We arranged T103C cysteine to laterally conjugate adjacent subunits. In the axis direction, we set A74C mutation and systematically investigated candidate from E50C to P54C as the other thiol function site, for forming longitudinal disulfide bond chains. Significantly, the T103C-TMV-E50C-A74C shows the highest robustness in assembly capability and structural stability with the largest length, for TMV VLP to date. The fibers with lengths from several to a dozen of micrometers even survive under pH 13. The robust nature of this TMV VLP allows for reducer-free synthesis of excellent electrocatalysts for application in harshly alkaline hydrogen evolution.