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DNA Origami‐Templated Aptamer Chiral Structures Realize Cellular Enantioselectivity
ABSTRACT Chirality refers to handedness as left‐ or right‐handed form of a molecule or molecular construct by synthesis or self‐assembly. In biology, chirality plays critical roles in determining the structures and functions of biomolecules such as proteins. In this study, we demonstrated that structural chirality generated by patterning multiple cell surface protein biomarker‐binding aptamers on a tubular‐shaped DNA origami (“DNA tube”) can realize differentness in cellular interaction, nanostructure uptake, cancer drug delivery, and consequent cell killing. Formation of the DNA tube and its ability to arrange external elements into left‐ or right‐handed form have been characterized by gel electrophoresis, atomic force microscopy, and transmission electron microscopy. Our fluorescence‐based cell experiments showed that the DNA tube‐templated aptamers of a left‐handed pattern can yield a higher cell uptake than those in a right‐form pattern. When loaded with an anticancer drug, Daunorubicin (Dau), the left‐handed tube‐aptamer‐Dau construct showed greater than double the cancer cell cytotoxicity than the construct in the right‐handed. Our study not only revealed that cell surface proteins interaction with the aptamers spatially organized into different chiral patterns can yield different cellular interaction and internalization efficiencies, but offered a new and versatile cancer drug delivery strategy for enhanced target cell treatment efficacy.
Metal‐Free Nanoarchitectonics of Fluorescent Transparent Materials via Co‐Assembling Non‐Aromatic Amino Acids and Tetrafluorophthalic Acid for Adhesion, Coating, and Information Encryption Applications
ABSTRACT Realizing fluorescence emission from non‐aromatic amino acids is a difficult challenge in the development of optical materials in the absence of polymeric backbones and covalent cross‐linkers. Herein, a non‐covalent approach is used to fabricate a series of bulk glasses exhibiting strong fluorescence from non‐aromatic amino acids (ʟ‐arginine, ʟ‐lysine, ʟ‐proline, and ʟ‐histidine) by co‐assembling them with tetrafluorophthalic acid ( FA ). FA , amino acids, and non‐covalent bonding between them play essential roles in both glass formation and fluorescent properties. The high viscosity and rapid annealing process of the glass formation process effectively prevent the crystallization and packing of FA and amino acids, slow the free internal rotations of the amino acids, and reduce the intermolecular collisions, thus increasing the fluorescence emissions of glasses. FA ‐amino acids glasses display high fluorescence quantum yields (> 44%) and large Stokes shifts. Their fluorescence performance is maintained even under various harsh conditions, including low temperatures, exposure to organic solvents, and coating with porous materials. Based on their robust anti‐freezing adhesion capacity (4.77 MPa at −40°C, 3.30 MPa at −196°C) and long‐term stable solid‐state luminescence characteristics, these materials show great potential as fluorescent coatings and labeling agents suitable for use at low temperatures.
Nanomedicine Reimagined: Translational Strategies for Precision Tumor Theranostics
Abstract Nanomedicine has shown remarkable promise in advancing tumor imaging and therapy through its ability to achieve targeted delivery, precision imaging, and therapeutic efficacy. However, translating these preclinical successes into clinical practice remains fraught with challenges, including inconsistent tumor targeting, off‐target organ accumulation, and a lack of comprehensive understanding of in vivo behavior of nanomedicines. In this perspective, the current state of nanomedicine research is critically analyzed, emphasizing the translational bottlenecks and offering a forward‐looking view on potential solutions. The enhanced permeability and retention (EPR) effect are revisited, dissecting its variable relevance across small animals, large animals, and human patients. Emerging strategies are also discussed to overcome its limitations, such as active targeting and bioengineered delivery systems. Highlighting the need for multimodal imaging, it is proposed to combine nuclear imaging for deep‐tissue penetration with high‐resolution optical imaging to refine our understanding of nanomedicine biodistribution and tumor targeting. Additionally, nonspecific uptake in organs like the liver and spleen is examined, advocating for strategies such as carrier surface modification and biomimetic design to enhance tumor specificity. Moving forward, integrate advanced technologies such as artificial intelligence (AI)‐driven data analytics and humanized in vitro and in vivo models are proposed to better predict clinical outcomes. By critically synthesizing the current knowledge and proposing transformative directions, this review aims to inspire innovative approaches that will pave the way for nanomedicines to achieve their full clinical potential in tumor theranostics.
Structural and functional insights into calmodulin-mediated lipid binding and proteolytic cleavage of the M-PMV matrix protein
Sentinel lymph node biopsy improves surgical management of cervical cancer
Bimetallic Cladding‐Constructed Interfacial Microenvironment Enabled Highly Reversible Powder Anode for Zn Metal Batteries
ABSTRACT The unstable interface of metal powder anode remains a challenge to achieve long‐life Zn powder‐based aqueous zinc metal batteries (AZMBs). However, most reported metal composite strategies still suffer from a mismatch between Zn 2+ diffusion and electron transfer behaviors. Here, a bimetallic cladding strategy with a specific displacement sequence was proposed. Except for inheriting intrinsic advantages of Sn and Cu, the opposite EDL charge distribution of Cu to Zn compensates for the anion adsorption, inhibiting the ZSH‐related side reactions. Moreover, abundant in situ constructed surface SnO 2 voids could accommodate stripped Zn 2+ to avoid disordered diffusion, providing a shorter diffusion distance for the electron acceptance by Zn 2+ instead of H + . Based on the matched electron and ion transport behaviors, the Zn@SC anode exhibited excellent cycle stability of over 2800 h in Zn||Zn cells at 1 mA cm −2 –5 mAh cm −2 , and achieved an areal capacity of 2 mAh cm −2 in Zn||NH 4 V 4 O 10 cells at 3 A g −1 and 70% capacity retention after 1000 cycles. As a practical validation, the pouch cell based on Zn@SC anode and high mass‐loaded cathode (10.05 mg cm −2 ) also exhibits satisfactory cycle stability. This work emphasized the importance of the interfacial microenvironment on the electrochemical performances and provided valuable direction of multi‐metal Zn powder anode.
Regulating the orientation of homobivalent small binders through 3D domain-swapping design
Differential Ligand–Cation Interactions Enable 2D‐Template‐Induced Ordered Assembly for Efficient Tin‐Based Perovskite Photovoltaics
ABSTRACT Environmentally friendly tin halide perovskite (THP) solar cells have recently attracted more and more research efforts as a promising alternative to toxic lead‐based perovskites. Incorporating more stable and uniformly oriented two‐dimensional (2D) phase components into the fast‐crystallizing and oxidation‐prone three‐dimensional (3D) phases as a growth template is a common strategy to enhance THP film quality. However, the simultaneous crystallization of the 2D phase with the 3D phase greatly undermines ordered crystallization for high‐performance THP devices. Herein, a fullerene derivative ligand is introduced to establish distinct ligand–cation interaction modes with the 2D and 3D components, thereby programming the A‐site cation‑mediated sequential assembly and crystallization. The 2D phase crystallizes first and serves as a template to guide the ordered epitaxial growth of the 3D phase, yielding a highly crystalline and oriented THP film with a homogeneous 2D/3D heterojunction as an efficient interface. The resulting devices achieve a significantly enhanced champion power conversion efficiency of 16.6%. Moreover, unencapsulated devices operating at maximum power point under continuous 1‐sun illumination and 50°C exhibit a nine‐fold longer T 90 lifetime (882 h vs. 99 h) compared to control devices.
ANP32A-mediated histone 3 K27 acetylation is essential for sotorasib activity in KRAS-mutant non–small cell lung cancer
Thread‐Designed Vascular Scaffold with Magneto‐Optical Probes Capture and Elimination of Circulating Tumor Cells In Vivo
ABSTRACT Metastasis, responsible for over 90% of cancer‐related deaths, is largely fueled by circulating tumor cells (CTCs). Although eliminating CTCs could inhibit metastasis, the complex in vivo environment makes it difficult. Considerable progress of in vitro CTCs detection has been made, yet its translation into effective in vivo systems, particularly for large animals, continues to pose a substantial challenge. This study introduces a threaded vascular scaffold that creates a cell‐enrichment zone by modulating radial fluid velocity, enhancing cell axiality and providing an optimized environment for CTCs capture. In addition, hybrid membranes‐modified magnetic beads (HM‐MBs) loaded with indocyanine green and coated with tumor‐white cell membranes, enabling specific recognition and binding of CTCs. Under external magnetic guidance, CTCs bound to HM‐MBs are efficiently accumulated at the scaffold site, followed by near‐infrared light‐triggered activation of photodynamic and photothermal effects for targeted CTCs elimination. This integrated system effectively addresses key challenges in in vivo CTCs detection and removal. Experimental results in rabbit and goat vessels demonstrated high capture efficiencies of 60.3% and 54.7%, respectively, along with post‐irradiation elimination rates exceeding 90%. This integrated approach enables targeted in vivo CTCs capture and destruction, disrupting the metastatic cascade and offering a promising strategy for adjuvant cancer therapy.
Colloidal Quantum Dot Liquid Lasers
ABSTRACT Thermal management of lasers fundamentally limits the upper limit of their output power as well as their operational stability. In this context, liquid‐state lasers exhibit an unparalleled advantage in power scalability and stability, owing to their highly efficient heat dissipation facilitated by continuous fluid circulation. Additionally, the intrinsic compatibility of liquid lasers with microfluidic platforms also holds great promise for integration into energy‐efficient, miniaturized photonic systems. Colloidal quantum dots (QDs), which are solution‐processed semiconductor nanocrystals, have emerged as highly versatile optical gain materials. While research over the past decade has been predominantly centered on solid‐state QD lasers made from densely packed QD films or composite matrices, there has been a recent surge of interest in exploring QDs in their native dispersion form as active gain media for liquid‐state lasers. This review provides a systematic overview of recent advances in QD‐based liquid lasers, detailing their operational principles, critical performance metrics, and highlighting their unique advantages. Moreover, we point out current technical bottlenecks and explore prospective strategies for overcoming these limitations to pave the way for practical QD‐based liquid lasing technologies.
Modulating Salt Dissociation and Solvent Immobilization Through Dipole Interactions in Polymer Electrolytes for Lithium Metal Batteries
Abstract Poly(vinylidene fluoride) (VDF)‐based solid polymer electrolytes (SPEs) show great potential for application in solid‐state lithium batteries. However, their poor ion transport capabilities and uncontrolled electrode/electrolyte interfacial reactions induced by residual solvents limit their overall electrochemical performance. To address these challenges, a LiTFSI‐replaced dual‐functional cationic covalent organic framework (COF) is strategically designed, denoted COF‐LiTFSI, as organic fillers into poly(vinylidene fluoride‐co‐hexafluoropropylene) (PVHF)‐based solid polymer electrolyte (SPE) to regulate Li + transport and electrode/electrolyte interface stability. The introduction of dipole interactions between cationic moieties embedded in the COF‐LiTFSI framework and Li salt significantly enhances dissociation, thereby improving Li⁺ transport and lowering the activation energy ( E a ), while the strong dipole interaction between residual N‐methylpyrrolidone (NMP) and the COF‐LiTFSI framework immobilizes the NMP molecule, markedly enhancing the electrochemical stability of the PVHF‐COF‐CPE with a Li metal anode. Consequently, the optimized PVHF‐COF‐CPE achieves a high room temperature ionic conductivity of 0.63 mS cm −1 . Furthermore, the Li/Li, Li/LFP (LiFePO 4 ), and Li/NCM811(LiNi 0.8 Co 0.1 Mn 0.1 O 2 ) cells equipped with PVHF‐COF‐CPE achieve remarkably stable cycling. This work presents a novel strategy to regulate ion transport and interface stability in VDF‐based SPEs by leveraging dipole interactions, enabling high‐performance solid‐state lithium batteries.
Versatile Room‐Temperature Phosphorescence Silk Fibroin Platforms for Sustainable and Biocompatible Multifunctional Interfaces
Abstract The development of sustainably sourced, biocompatible room‐temperature phosphorescence (RTP) materials with rich formats, multimodal tunability, and multifunctional capabilities presents a transformative opportunity for sustainable technologies and biomedical interfaces, yet it remains a significant challenge. Here, RTP silk fibroin systems that feature improved processability, responsiveness, and functionality by multivalently anchoring phosphors to a versatile protein matrix are reported. The RTP silk fibroin can be processed into various fully biodegradable platforms, exhibiting strong RTP emission with a lifetime of up to 233 ms driven by multiple robust phosphor–fibroin interactions. The resulting platforms exhibit multi‐responsiveness to UV light, vapor, and temperature, along with diversified functionalities that include recyclability, weldability, morphability, and adhesion. Moreover, their adaptability with diverse micro/nano‐processing techniques enables complex RTP patterning and multidimensional information integration. Finally, it is demonstrated that these convergent advantages endow the platforms with multifunctionality and multi‐interface compatibility, enabling applications such as smart labels for electronic devices, conformal networks for pharmaceuticals, and scalable textiles for face masks.
Hyaluronic acid regulates cellular UDP-GlcNAc levels through CD44 to affect glycosylation and cell biological functions
T-DXd shows promise in neoadjuvant therapy for HER2+ breast cancer
Stiffness‐Gated Cytoplasmic mRNA Delivery Through Engineered Membrane Fusion for Breast Cancer Immunotherapy
ABSTRACT Traditional lipid nanoparticles (LNPs) suffer from low lysosomal escape efficiency (<4%) and off‐target toxicity, hindering mRNA therapy translation. While membrane fusion carriers bypass endosomal entrapment, their lack of cell specificity induces non‐target cytotoxicity. To overcome these limitations, we developed a stiffness‐gated mRNA delivery platform (PGC@FM). This system features a PLGA core loaded with G0‐C14 dendrimer/mRNA complexes and coated with an engineered, low‐stiffness tumor cell fusion membrane (FM). The membrane stiffness is strategically reduced via unsaturated fatty acid enrichment, enabling direct cytoplasmic delivery through selective fusion with low‐stiffness target cells. Conversely, encountering high‐stiffness non‐target cells, PGC@FM undergoes endocytosis and lysosomal degradation, minimizing off‐target effects. Compared to LNPs, this stiffness‐gated strategy enhanced EGFP‐mRNA transfection efficiency in 4T1 cells by 5.2‐fold and increased tumor‐specific p53‐mRNA delivery efficiency by 4.2‐fold, resulting in potent tumor suppression and immune activation. Crucially, non‐target cells rapidly degrade internalized PGC@FM in lysosomes, significantly reducing off‐target toxicity compared to conventional fusion carriers. These research results indicate that by leveraging the biophysical principle of membrane rigidity compatibility, highly selective mRNA delivery can be achieved, providing new ideas for the development of mRNA delivery carriers.
Allosteric zinc inhibition and interdomain regulation govern the catalytic mechanism of the E3-independent ubiquitin-conjugating enzyme hUBE2O
High Temporal‐Resolution Imaging Single Immune Cell Migration in Vivo by Ultrabright NIR‐II Organic Probes
ABSTRACT Given the implications of immune cell migration and cellular interaction in immune‐oncology, infectious and inflammatory diseases, there is a long‐standing interest in understanding, predicting, and ultimately manipulating immune cell migration therapeutically. However, real‐time non‐invasive in vivo immune cell tracking is considerably more challenging than static imaging, particularly when imaging highly motile cells. Here we introduce high‐brightness second near‐infrared (NIR‐II, 1000–1700 nm) window organic probes (DCPDs, brightness > 5000 M −1 cm −1 in aqueous solution), enabling non‐invasive high‐speed single immune cell imaging in the brain with a temporal resolution up to ∼50 fps. The neutrophil migration patterns in the stroke mouse brain and their interactions with infused therapeutic mesenchymal stem cells can be profiled with real temporal dynamics. This advancement facilitates fundamental studies on understanding complex cellular functions in vivo, paving the way for investigating the effect of single‐cell temporal dynamics on immune responses or disease‐related biological processes.
Homology‐Guided Zwitterionic Interlayers for 21% Efficiency Non‐Fullerene Organic Solar Cells
ABSTRACT The performance evolution of organic solar cells (OSCs) is increasingly constrained by a growing mismatch between state‐of‐the‐art photoactive layers and conventional cathode interlayer materials (CIMs). Here, we report a homology‐guided molecular design strategy to synchronize CIM with fused‐ring electron acceptors (FREAs). Grafting zwitterionic sidechains onto the high‐performance pentacyclic FREA, we created a novel CIM, SZ1. This design grants SZ1 a deeper lowest unoccupied molecular orbital energy level, higher electron mobility, and superior interfacial compatibility compared to the perylene diimides‐based counterpart. SZ1 simultaneously lowers the cathode work function and elevates the active layer's work function, facilitating Ohmic contact and enhancing electron extraction. SZ1 also acts as a supplemental light‐harvester, with hole/energy transfer at the SZ1/polymer interface contributing to photocurrent generation. These attributes make SZ1 a highly efficient and versatile CIM with an optimal thickness near 30 nm and exceptional thickness tolerance, retaining ∼89% of peak performance even at a thick interlayer of 90 nm. An impressive efficiency of 21.07% is achieved, ranking among the most efficient OSCs. The generality of this homology concept is demonstrated by its successful extension to non‐fused ring electron acceptors. This work establishes a transformative design paradigm for multifunctional, thickness‐insensitive interlayers, paving the way for commercially viable OSCs.