Colloidal quantum dots (QDs) in the second near-infrared (NIR-II, 0.9-1.7 mu m) window are enabling broader applications due to their tunable bandgaps, scalable solution-phase synthesis, and compatibility with flexible substrates and micro-/nanoscale fabrication. The low scattering of NIR-II light permits deeper penetration in both atmospheric and biological environments. Consequently, these QDs can be incorporated into compact NIR-II systems for nocturnal surveillance and autonomous driving scene perception, sustaining reliable operation under adverse scenarios, such as haze and smoke. They can also act as NIR-II fluorescent probes for deep-tissue imaging, providing improved spatiotemporal resolution owing to the greatly diminished scattering of NIR-II radiation in biological tissues and the much lower autofluorescence background.Silver chalcogenide QDs (Ag2X, X = S, Se, or Te) display both excitation and emission within the NIR-II region. Their low solubility product constants impart chemical stability and high photostability. Silver chalcogenide QDs are also considered more ecologically sustainable and have shown favorable biocompatibility. Our group first reported Ag2S QDs exhibiting NIR-II fluorescence, followed by the subsequent development of Ag2Se and Ag2Te. Drawing on our studies of silver chalcogenide QDs and insights into multiscale structure-property correlations, this Account systematically summarizes approaches to improve optical performance via rational design and precise synthetic control. Remaining challenges and future prospects in this area are also examined with the aim to promote further refinement and regulation of optical characteristics in silver chalcogenide QDs to satisfy demands in optoelectronics and biological fluorescence imaging. We anticipate this Account will serve as a valuable reference for research on the synthesis and optical properties of silver chalcogenide NIR-II QDs and their applications in photonic and bioimaging technologies.

Immunotherapy has shown enormous promise for cancer treatment, yet its efficacy is often hindered by the highly immunosuppressive tumor microenvironment (TME). Here, we developed a pH-responsive and cRGD-modified multifunctional liposomal system (FP2@PSLR) to co-deliver an immunogenic cytotoxic peptide (FR) and the PI3Kγ inhibitor IPI549 for coordinated TME remodeling. FR induces immunogenic cell death while exerting direct cytolytic activity, whereas IPI549 promotes macrophage repolarization toward the pro-inflammatory M1-like phenotype, enabling synergistic relief of immune suppression. FP2@PSLR, constructed from acid-sensitive lipids via reverse-phase evaporation, exhibited a uniform size (∼156 nm), high encapsulation efficiencies, excellent physiological stability, and rapid drug release under mildly acidic conditions. In vitro, the liposomes showed good biocompatibility, reduced hemolysis, effective immunogenic cell death induction, dendritic cell activation, and macrophage repolarization. In a 4T1 tumor model, FP2@PSLR demonstrated prolonged circulation, strong αvβ3 integrin-mediated tumor targeting, and clear NIR-II fluorescence for real-time tracking. Treatment resulted in significant TME reprogramming, including enhanced CD8+ T-cell infiltration, increased immune memory formation, and potent antitumor effects without systemic toxicity. These findings highlight FP2@PSLR as a rationally engineered nanoplatform capable of enhancing antitumor immunity through multi-pathway modulation of the immunosuppressive TME.

Monoclonal antibodies (mAbs) targeting the human epidermal growth factor receptor 2 (HER2) are widely used in the treatment of breast, gastric, and other solid tumors. However, rapid HER2 endocytosis and recycling contribute to low response rates and treatment resistance. Here, we introduce RhuA-P, a self-assembling protein that forms uniform, micron-sized 2D arrays (2.4 × 2.4 μm) featuring spatially addressable Protein G sites for mAb conjugation. This design allows control over antibody density (22-274 molecules per array) and intermolecular spacing (57-230 nm). We show that trastuzumab (TmAb) arrays templated on RhuA-P inhibit HER2 dimerization, cluster HER2 into micron-scale inactive domains dictated by the 2D TmAb geometry, and prolong receptor membrane retention by blocking endocytosis. This sustained blockade of HER2 signaling induces oxidative stress and triggers potent apoptosis. In a murine breast cancer model, TmAb arrays exhibited superior antitumor efficacy compared to free TmAb. Moreover, the modular design of RhuA-P makes it a versatile platform for assembling other clinically relevant mAbs─such as anti-PD-1 and anti-PD-L1 antibodies─offering a generalized strategy for enhancing antibody-based therapies.

ABSTRACT Precise activation of ion channels enables fine-tuned control of neuronal excitability, providing a powerful strategy for dissecting and modulating neural circuits. Although optogenetics offers high spatiotemporal neuronal manipulation with cell-type specificity, its reliance on visible light (400-650 nm) limits tissue penetration to millimeter depths, restricting applications in deep-brain stimulation. Here we report a near-infrared-II (NIR-II)-sensitive calcium channel, HaloNeu, created by genetically fusing a circularly permuted HaloTag (cpHaloTag) to the thermo-sensitive transient receptor potential vanilloid 1 (TRPV1) and covalently conjugating NIR-II photothermal nanotransducers (HPN). The HaloNeu enables non-invasive neuromodulation at depths up to 1.0 cm at ultralow laser power (∼60 mW/cm 2 ) and up to 5.0 cm under the safe exposure limit (∼1 W/cm 2 ) with 1064 nm laser illumination. Remarkably, HaloNeu maintains stable, on-demand neuron-specific modulation for over two months in vivo , providing sustained activation of ventral tegmental area (VTA) circuits and effective alleviation of Parkinsonian symptoms in mouse models. These results establish HaloNeu as a robust and versatile platform for cell-type-specific, deep-tissue, and chronic neuromodulation, with broad implications for neuroscience and neurotherapeutics.

The precise programming of bond valency, interaction strength, and spatial positioning within protein assemblies represents a significant step toward addressable functionalization, affording refined control over pattern recognition, cooperative behavior, and structural self-organization. Here, we introduce a generalizable strategy to regulate the valency of symmetric protein assemblies through a shape-complementary DNA scaffold. We demonstrate the controlled transfer of streptavidin-DNA conjugates from a ring-shaped DNA nanostructure to a recombinant tobacco mosaic virus (TMV) disk. This mechanism specifies the number, sequence identity, and spatial arrangement of DNA motifs along the disk periphery, thereby enabling site-specific addressability for DNA-mediated binding and functional labeling. Leveraging the intrinsic programmability of DNA nanostructures, this strategy establishes a versatile platform for high-fidelity valency engineering across diverse protein modules, with potential applications in biomedical and bioengineering.

Solution-processed short-wave infrared (SWIR) photodetectors utilizing colloidal quantum dots (QDs) represent a transformative advancement in next-generation infrared optoelectronics. Although environmentally benign silver telluride (Ag2Te) QDs have shown promise for SWIR detection, the performance of such devices, especially beyond 1.5 u03BCm, remains constrained by inadequate energy-level alignment at heterojunctions and insufficient passivation of interfacial defects. This study introduces an inorganic bismuth chloride (BiCl3) interlayer between the SnO2 electron transport layer and the Ag2Te QD active layer. This modification simultaneously facilitates effective defect passivation and optimized band alignment, leading to a significant improvement in photocarrier collection efficiency. The resulting BiCl3-modified Ag2Te QD photodiodes achieve a record external quantum efficiency (EQE) of approximately 20% at 1540 nm under zero bias, along with a specific detectivity (D*) of 2.3 u00D7 1011 Jones at room temperature. This work provides valuable insights into interface engineering for developing high-performance eco-friendly SWIR QD optoelectronic devices.

Fluorescence lifetime extends optical multiplexing capability by exploiting the temporal dimension and offers new opportunities in optical-based applications. However, lifetime adjustment generally relied on varying fluorophor content. We herein show that β-NaYbF4:Er@NaYbF4:Nd core-shell nanocrystals exhibit an excitation power-dependent lifetime of 1532 nm emission, making it possible to control lifetime without the necessity of altering the material. We demonstrate that a nonlinear multiphoton process accompanying with nonradiative relaxation occurs in the downshifting emission. This proposal was confirmed by perturbed-population-dynamics calculations and the dependence of the energy pathway on temperature and Yb3+ in the sublattice. Furthermore, we demonstrate dynamic, multidimensional anti-counterfeiting patterns using a single nanocrystal type to achieve multicolor lifetime patterns. Our work reveals a variable lifetime in unaltered nanoparticles, arising from multiphoton processes in downshifting emission, which may inspire the development of novel photonic nanomaterials for applications such as optical communication, information storage, optical sensors, and photonic computing.

Precise ion-channel activation enables fine control of neuronal excitability and neural circuits. Although optogenetics enables cell-type-specific neuronal control, its reliance on visible light (400-650 nm) limits tissue penetration and restricts deep-brain stimulation. Here we report a near-infrared-II (NIR-II)-sensitive calcium channel, HaloNeu, created by genetically fusing circularly permuted HaloTag (cpHaloTag) to thermo-sensitive transient receptor potential vanilloid 1 (TRPV1) and covalently conjugating NIR-II photothermal nanotransducers (HPN). The HaloNeu enables non-invasive neuromodulation at depths up to 1.0 cm at ultralow laser power (~60 mW/cm2) and up to 5.0 cm under the safe exposure limit (~1 W/cm2) with 1064 nm illumination. Remarkably, HaloNeu maintains stable, on-demand neuron-specific modulation for over two months, providing sustained activation of ventral tegmental area (VTA) circuits and effective alleviation of Parkinsonian symptoms in mouse models. These results establish HaloNeu as a robust and versatile platform for cell-type-specific, deep-tissue, and chronic neuromodulation, with broad implications for neuroscience and neurotherapeutics.

Second near-infrared (NIR-II, 900–1700 nm) fluorescence imaging, characterized by significantly reduced autofluorescence interference, enhanced tissue penetration, and improved in vivo resolution, has emerged as a promising modality for intraoperative tumor...

Tumor-associated macrophages (TAMs) are key regulators of the tumor microenvironment (TME). They typically adopt an M2-like phenotype that promotes tumor progression by providing survival signals, suppressing anti-tumor immunity, and facilitating pre-metastatic niche formation. Reprogramming TAMs toward an anti-tumor phenotype has emerged as a promising therapeutic strategy, with the repolarization of M2-like TAMs into an M1-like phenotype being central to this approach. Here, a nitric oxide (NO)-activatable near-infrared-II (NIR-II) fluorescence/photoacoustic nanoinducer (I/E@M2pep) that selectively targets M2-like TAMs and reprograms them toward an M1-like phenotype, thereby enhancing anti-tumor efficacy is reported. In this construct, the M2pep peptide enables M2-like TAM targeting, IPI549 reprograms them toward an M1-like phenotype while inducing NO production, and the NO-activatable NIR-II probe (ETNO) allows for in vivo visualization of macrophage repolarization via NIR-II fluorescence/photoacoustic imaging. In a mouse breast cancer model, intravenous administration of I/E@M2pep produced a ratiometric NIR-II photoacoustic signal change that correlated with M2-to-M1 repolarization. Furthermore, combining this nanoinducer with a CD47 monoclonal antibody markedly enhanced anti-tumor immunity through M1 macrophage-mediated tumor killing and TME remodeling. This work presents an effective in vivo strategy that simultaneously facilitates and visualizes TAM repolarization, holding promise for broader applications in studying tumor initiation, metastasis, and treatment response.

Solution-processed short-wave infrared (SWIR) photodetectors utilizing colloidal quantum dots (QDs) represent a transformative advancement in next-generation infrared optoelectronics. Although environmentally benign silver telluride (Ag2Te) QDs have shown promise for SWIR detection, the performance of such devices, especially beyond 1.5 mu m, remains constrained by inadequate energy-level alignment at heterojunctions and insufficient passivation of interfacial defects. This study introduces an inorganic bismuth chloride (BiCl3) interlayer between the SnO2 electron transport layer and the Ag2Te QD active layer. This modification simultaneously facilitates effective defect passivation and optimized band alignment, leading to a significant improvement in photocarrier collection efficiency. The resulting BiCl3-modified Ag2Te QD photodiodes achieve a record external quantum efficiency (EQE) of approximately 20% at 1540 nm under zero bias, along with a specific detectivity (D*) of 2.3 & times; 1011 Jones at room temperature. This work provides valuable insights into interface engineering for developing high-performance eco-friendly SWIR QD optoelectronic devices.

Colloidal quantum dots (QDs) exhibit exceptional triplet sensitization capabilities for near-infrared (NIR)-to-visible photon upconversion (UC) via triplet-triplet annihilation (TTA). Although eco-friendly lead-free QDs hold promise as NIR sensitizers, the development of NIR Ag-based QD TTA-UC system remains in its infancy. In this work, we employ AgAuSe QDs as NIR-harvesting sensitizers and demonstrate that surface ligands dictate the feasibility of triplet energy transfer (TET). Thiol ligands are essential for passivating QD surface to achieve high quantum yield, while their strong affinity with Ag+ and Au+ in AgAuSe QDs inhibits the binding of triplet energy transmitter molecules, thereby preventing TET. In contrast, amine-capped AgAuSe QDs enable efficient TET, achieving an upconversion efficiency of 21.5% (normalized to 100%). Moreover, our strategy is universally applicable to NIR-to-visible UC using other Ag-based QDs such as Ag2S. These findings overcome a critical bottleneck that has impeded TET in Ag-based QDs, thereby unlocking their potential for a new generation of UC materials.

Controlled three-dimensional chiral arrangement of plasmonic nanocomponents is crucial for understanding emergent light-matter interactions but remains challenging, particularly for heterogeneous plasmonic nanoparticles with distinct shape anisotropy. Here, using an elaborately designed DNA assembly strategy, we constructed hybrid chiral plasmonic systems integrating gold nanodisks and nanorods. Chiroptical activity arises from the asymmetric lateral displacement between them, and the sign and intensity of the circular dichroism are determined by the number and handedness of the nanorod arrangements. We reveal that this chiroptical activity originates from selective plasmonic coupling between the in-plane resonance of the nanodisks and the longitudinal resonance of the nanorods, representing an experimental realization of an extended plasmonic Born-Kuhn model. This work opens new avenues in plasmonics and nanophotonics by providing a design paradigm for constructing complex chiral architectures.

Rapid diagnostic technology serves as a cornerstone of clinical medicine, playing an essential role in the early detection of major diseases and the development of personalized treatment strategies. The complexity and diversity of clinical diagnostic needs impose increasingly stringent demands on the timeliness, sensitivity, and specificity of detection techniques─requirements that current methods often fail to fully satisfy. Near-infrared II (NIR-II) fluorescence imaging has emerged as a highly promising visualization tool for rapid diagnosis, owing to its deep tissue penetration, high spatial resolution, excellent signal-to-background ratio, and real-time feedback capabilities. As advanced fluorescent nanomaterials, quantum dots (QDs) provide a powerful technological pathway to address the aforementioned clinical challenges. This Account systematically summarizes our recent research progress in this field from three key perspectives: First, we outline the design strategies, photophysical properties, and biosafety profiles of NIR-II-emitting I-VI QDs. Second, we comprehensively discuss strategies for achieving rapid and highly sensitive fluorescence detection, including self-assembly based multivalent anchoring, competitive absorption suppression, and mechanisms such as fluorescence resonance energy transfer (FRET) and chemiluminescence resonance energy transfer (CRET). Furthermore, representative applications of these technologies in in vivo visualization and clinical sample diagnostics are summarized, covering precise tumor margin delineation and micrometastasis detection, dynamic monitoring of vascular pathologies, and early assessment of inflammation and injury. Finally, we highlight the advantages of NIR-II fluorescent probes in diagnostic research, critically analyze existing challenges, and offer insights into future developmental directions.

The geometric nature of anisotropic nanoparticles (NPs) gives rise to directional variations in their physicochemical properties, making the characteristics of their assemblies highly tunable by manipulating their three-dimensional (3D) spatial configurations. Surface modification with DNA ligands, which creates molecular recognition between NPs, offers a practical approach for self-assembling NPs into customized nanostructures with emergent collective properties. However, the regioselective modification of DNA ligands on the complex 3D surface of anisotropic NPs to create specific and directional bonds remains challenging. Here, taking gold nanorods (AuNRs) as representative anisotropic NPs, we develop a DNA ligand encoding strategy that chemically transfers the two-dimensional (2D) DNA patterns from DNA origami templates onto the 3D curved surface of AuNRs, programming their valence and orientation for self-assembly. A semiflexible DNA origami template is designed to wrap around the AuNR to ensure that customized DNA ligands are addressed to predetermined positions. These DNA ligands facilitate specific linkages between AuNRs and gold nanospheres (AuNSs), enabling the construction of various stereocontrolled AuNR-AuNS nanostructures. By regulating the arrangement shape of DNA ligands and combining sequence-orthogonal DNA ligands, we further demonstrate precise control over the orientation of individual AuNRs, allowing the assembly of AuNR structures with tunable optical chirality. This approach provides a versatile strategy for assembling anisotropic NPs into desired 3D structures in a scaffold-free manner, which advances the construction of promising nanodevices for photonic, information, and biomedical applications.

Hydrophilic semiconductor quantum dots (QDs) with photoluminescence (PL) located in the second near-infrared window (NIR-II) have demonstrated great promise for in vivo bioimaging applications. However, their performance can be affected...

Chimeric antigen receptor (CAR)-T cells have shown unparalleled efficacy in treating hematologic cancers, but their application in solid tumor treatment remains challenging due to the immunosuppressive tumor microenvironment (TME). It is highly significant to develop safe and efficient TME regulatory strategies for the adoptive cellular immunotherapy of tumors. Herein, a TME-responsive nanoimmunomodulator (FMANAC) is designed using a multicomponent coordination self-assembly method to reconstruct the immune chemokine gradient and overcome the suppression of CAR-T cell immunoactivity, thereby improving the infiltration and killing efficiency of CAR-T cells within tumors. The acidic TME induces the disassembly of FMANAC, followed by the drug release, in which C-C chemokine ligand 5 (CCL5) improves the disrupted chemotactic gradient within tumors, increasing CAR-T cell recruitment and infiltration into deep tissue; and NLG919 reverses indoleamine 2,3-dioxygenase (IDO)-mediated immunosuppression in TME to create a favorable environment for CAR-T cells to exert their killing function. In the H460 lung cancer animal model, this nanoregulatory strategy combined with engineered CD276 CAR-T cells, guided by multiplexed near-infrared-II fluorescence imaging for programmed administration, achieved significantly enhanced tumor treatment efficacy.

Lattice engineering in lanthanide nanocrystals (LnNCs) is fundamental for tailoring their versatile optical properties, yet it remains underexplored in manipulating the downconversion characteristics. Here, we engineer the lattices from distorted to strain-graded in LnNCs by CaF2 deposition on vacancy-controlled beta-NaxGdF3+x:Yb,A (A = Tm/Er, x = 0.5, 0.75, 1) NCs. We demonstrate that strain-graded lattices with high phonon energy enhance the multi-phonon orbit-lattice relaxation (MPR) in the downconversion process more effectively than distorted lattices, which helps to extend the near-infrared-IIb (NIR-IIb, 1500-1700 nm) lifetime of Er3+/Tm3+ by 2 similar to 4 times. Subsequent epitaxial CaF2 growth further attenuates surface phonon coupling, enabling exponential tunability of NIR-IIb lifetime (Tm3+: 0.74 similar to 6.28 ms; Er3+: 0.055 similar to 9.2 ms). Finally, we showcase the potential of these LnNCs in time-resolved multiplexed bioimaging.

The unique plasmonic resonance properties, surface‐enhanced catalytic efficiency, and exceptional chemical inertness of gold nanoparticles (AuNPs) make them highly promising for a wide range of interdisciplinary applications. A critical factor in their functional utility is the precise spatial organization of AuNPs, where controlled assembly enhances emergent properties—such as collective plasmon coupling for sub‐wavelength light manipulation, amplified catalytic hot‐spot generation, and programmable mechanical responsiveness—that are unattainable in isolated particles. Despite these advantages, achieving precise architectural control over AuNPs remains a significant challenge. Multidimensional protein templates offer a compelling solution, exploiting stereochemical specificity to direct AuNP assembly or Au 3+ reduction into gold nanostructures (AuNSs) with tunable dimensionality—1D nanowires, 2D arrays, and 3D crystals. This review systematically assesses recent advancements and the current state of AuNSs directed by protein templates, encompassing strong bond‐like, relatively weak, and noncovalent interactions, and the latest strategies that facilitate the formation of multidimensional AuNSs. Additionally, the unique properties and applications of AuNSs in sensing, catalysis, solar cells, biofuel cells, bioimaging, and tissue engineering are discussed. Finally, key challenges and future opportunities—including precise multidimensional assembly, environmental stability, manufacturing scalability, and the integration of theory‐driven research paradigms—are discussed.