Huayu Tian

Precise optical signal regulation is essential for diagnostic tools; however, most existing systems suffer from inefficient off-state quenching due to limited control over intermolecular interactions and are often constrained by single-modality outputs. Herein, we introduce a self-assembly guided quenching framework, termed Assembly-Improved Dye-quenching Efficiency (AIDE), which integrates Förster resonance energy transfer (FRET) and aggregation-caused quenching (ACQ) within a cooperative nanoscale architecture to enhance off-state suppression. As a representative implementation, AIDE is realized using tin(IV) naphthalocyanine (SnPc), a near-infrared chromophore with a high extinction coefficient and strong aggregation propensity. When combined with infrared fluorophores, SnPc functions as both a FRET acceptor and an ACQ scaffold, enabling near-complete fluorescence suppression (>99%) through assembly-dependent energy dissipation beyond conventional molecular designs. By introducing biomarker-cleavable linkers, we construct single-stimulus, dual-responsive multimodal nanoreporters (SDMRs) that integrate near-infrared fluorescence, photoacoustic imaging, and renal-clearable urinary readouts upon activation, thereby extending output signal wavelengths and expanding quencher functionality. Notably, SDMRs exhibit intrinsic tropism for inflamed tissues. In rodent models, this trimodal platform enables early detection of tumors (∼6 mm) and skin allograft rejection (24 h post-transplantation). Together, AIDE establishes a generalizable framework for high-contrast, multimodal, and minimally invasive disease diagnostics.

Although hydrogels with antimicrobial and monitoring have the potential for precision wound therapy, it is difficult to construct smart framework of hydrogels in molecular level. Herein, an in situ crosslinked antimicrobial conductive hydrogel (Au/HA‐TPP) based on 5,10,15,20‐tetra(4‐ N ‐(4‐boronobenzyl)pyridin) porphyrin (TBPP) and hyaluronic acid (HA) was prepared triggered by an alkaline solution containing Au(III) reduction catalysis with phenylboronic acid, (5,10,15,20‐tetra(4‐dihydroxyborylphenyl) porphyrin (TBP) and 5,10,15,20‐tetrakis‐(4‐N‐methylpyridyl) porphyrin (TMPyP)) as control. In the process of gelation, Au(III) was reduced into Au nanoparticles (Au NPs) and formed into nanoparticles and dispersed evenly in Au/HA‐TPP with fastest gelation time of 22 s and the best mechanical properties. The synergistic interaction of Au NPs and porphyrins can induce effective antibacterial photodynamic therapy (APDT) under visible light irradiation, and the photothermal effect caused by Au NPs had a fast temperature rise in seconds with good cycling stability. In addition, quaternized porphyrins in Au/HA‐TPP played a long‐term antibacterial and APDT effects. The dynamic change of the contact resistance between the hydrogel and wounds can reflect the wound healing to achieve instantaneous monitoring. Au/HA‐TPP hydrogels integrated multimodal sterilizations as well as the realization of intelligent wound detection, which could provide the diagnosis and treatment of infected wounds at different application scenarios.

Lipid nanoparticles (LNPs) have become a clinically established platform for mRNA vaccine delivery, demonstrating significant potential in both infectious disease and cancer immunotherapy. However, excessive intracellular reactive oxygen species (ROS) can impair protein synthesis and compromise vaccine efficacy. To address this limitation, we developed an ionizable lipid incorporating a dopamine-derived moiety (DA lipid) for the formulation of ROS-scavenging LNPs. Comparative studies with oxidized control LNPs (ODA LNPs) revealed that DA LNPs exhibit superior intrinsic antioxidant activity, effectively mitigating intracellular ROS accumulation while supporting higher mRNA-derived protein expression. DA LNPs mediated transfection levels comparable to those achieved with ALC-0315 LNPs (ALC LNPs). In addition, DA LNPs induced stronger antigen-specific immune responses and more potent tumor suppression in a prophylactic mouse melanoma model compared to ODA LNPs. These results support the importance of redox modulation in optimizing mRNA vaccine performance and provide a rational design strategy for advanced nucleic acid delivery systems.

Accurate and early detection of pneumonia is crucial for effective treatment; however, current diagnostic methods often lack the necessary specificity and sensitivity. Herein, we begin with a comprehensive bioinformatics analysis, identifying neutrophil elastase (NE) as a critical biomarker associated with pneumonia progression. We subsequently develop an NE-responsive probe (NERP), composed of a hemicyanine fluorophore linked to an NE-sensitive peptide, specifically designed for activation in inflamed tissues. To facilitate urinalysis, NERP is further refined into a hydrophilic active targeting responsive probe (ATRP _H ). ATRP _H demonstrates exceptional sensitivity in both in vivo imaging and urine-based detection, with urine analysis offering a noninvasive, early-stage diagnostic option that overcomes the limitations of tissue penetration and low accuracy. In addition, ATRP _H is highly effective in drug screening, dosage optimization, and exploring mechanisms of NE production. This biomarker screening and design strategy not only enhances pneumonia diagnosis and treatment via different routes of administration but also has broader potential for other inflammatory lung diseases.