Xiaoyu Wang

Efficient photodynamic antibacterial activity relies on the close interfacial association between photosensitizers and bacterial surfaces. While cationic functional groups can enhance bacterial binding, they often cause nonspecific membrane disruption and substantial dark toxicity. Here, we demonstrate that engineering a mixed-charge surface on conjugated oligomer nanoparticles enables programmable interfacial interactions and, consequently, controllable antibacterial performance. Charge-complementary conjugated oligomers, OFTF(+) bearing quaternary ammonium groups, and OFTF(-) bearing carboxyl groups, were assembled into photofunctional nanoparticles (OFTFNPs) by controlling their molar ratio. The mixed-charge surface maintained stable bacterial binding while reducing the overly strong electrostatic contact. This shifted the dominant interaction contribution toward hydrophobic association, thereby reducing nonspecific damage. Based on the balanced nano-bio interface, OFTFNPs predominantly generate reactive oxygen species via a Type II mechanism upon light irradiation, achieving the eradication of bacteria with minimal dark toxicity and improved cytocompatibility relative to OFTF(+) alone. These results demonstrate that mixed-charge surface engineering is a practical approach for separating potent photodynamic antibacterial efficacy from cationic dark cytotoxicity in photosensitizer platforms.

Controlled interfacial polymerization in conventional or Pickering emulsions enables the precise fabrication of cavity‐like architectures, providing a versatile platform for the composite construction. Fluorescent gold nanoclusters, acting as interfacial stabilizers, not only enhance emulsion stability but also simultaneously impart luminescent properties to the resulting composites. In this study, modified gold nanoclusters were used as one of the monomers in the interfacial polymerization process to prepare emulsions with fluorescent properties. These gold nanoclusters were localized on the droplet surfaces, forming spherical shell structures. To further enhance the functionality of these structures, we incorporated an additional fluorescent dye as a filler within the spherical shells, resulting in microcomposites with unique optical characteristics. The combination of two luminophores produced white luminescence, which could shift to different colors depending on the incident light. This innovative approach offers new possibilities for applications of advanced optical technologies.

Rapid, highly sensitive, and specific nucleic acid detection plays a crucial role in advancing point-of-care (POC) diagnostics for pathogens and viruses, cancer monitoring, and optimizing clinical treatments. Herein, leveraging the precise recognition ability of CRISPR/dCas9 and the powerful localized surface plasmon resonance (LSPR) of gold nanoparticles (AuNPs), we report the design of a dual protein corona-mediated detection platform to simultaneously fulfill rapid POC testing and single-molecule counting of nucleic acids in a one-pot and one-step manner. This system uses guide RNA as a molecular bridge to anchor dCas9 protein onto AuNPs, forming artificial protein coronas. Upon recognizing a target, the interaction between the two protein coronas on the same nucleic acid molecule triggers cross-linked aggregation of AuNPs. Then, a target as low as 100 aM can be visually detected within 30 min, making the platform particularly well-suited for rapid POC application and the screening of emerging epidemics. Additionally, the superior LSPR properties of AuNPs increase the light-scattering signal generated during target-induced aggregation, enabling the visualization of the aggregated AuNPs as diffraction-limited spots under confocal microscopy. By counting these spots, the platform achieves unprecedented detection sensitivity, identifying a target as low as 1 aM, which is equivalent to just 6 molecules in a 10 μL system, demonstrating single-molecule detection capability. This dual protein corona-mediated detection system offers exceptional promise for large-scale screening of pathogenic viruses and the early detection of cancer, particularly in applications requiring ultrahigh sensitivity at the single-molecule level.

Gold nanoclusters (AuNCs), which are approximately 2 nm in size, exhibit distinctive photophysical and catalytic properties, but their performance is often compromised by environmental factors. To mitigate these challenges, attempts have been made to incorporate AuNCs into polymer matrices to enhance their stability. Miniemulsion polymerization has proven to be an effective method for fabricating organic‐inorganic composites. Here, we present a facile photothermal‐assisted method for miniemulsion polymerization utilizing AuNCs, which serve as co‐stabilizers of the emulsion and photothermal conversion agents. By grafting tryptamine onto hydrophilic AuNCs, the amphiphilic AuNCs were spontaneously adsorbed at the styrene/water interfaces, resulting in stable nanoemulsions. Taking advantage of the photothermal properties of surface‐bounded AuNCs, rapid polymerization of styrene within the nanoemulsion was successfully initiated by external laser irradiation. The prepared nanocomposites inherited the photothermal activity of AuNCs and exhibited good photothermal stability and repeatability. This approach not only facilitates remote control of chemical reactions, but also optimizes the distribution of AuNCs within the final polymer matrix, thereby enabling the efficient synthesis of nanocomposites while exploiting the unique photofunctionality of AuNCs.

Chemo/photothermal combination therapy is a promising and practical approach for cancer treatment which calls for certain nanovehicles to achieve the spatiotemporal co-occurrence of photothermal conversion and drug delivery. Herein, we developed a montmorillonite-based Pickering emulsion equipped with a near-infrared photothermal agent (indocyanine green, ICG) and anticarcinogen (paclitaxel, PTX). With both montmorillonite and ICG functioning as interfacial stabilizers, the Pickering emulsion showed good stability and nanoscale droplet size, which were favored for cellular applications. Due to the vast oil-water interface, where the majority of amphiphilic ICG was prone to distribute, the Pickering nanoemulsion could achieve a higher local concentration of ICG than the aqueous solution, therefore leading to a higher local photothermal performance under near-infrared irradiation. The Pickering nanoemulsion exhibited fast cell penetration, which promoted the photothermal therapeutic effect of ICG. Moreover, the inner phase of the Pickering nanoemulsion also facilitated the loading of PTX, further improving its killing efficacy against cancer cells under near-infrared irradiation, because the photothermal conversion of the Pickering nanoemulsion could not only cause heat damage by itself but also promote the loaded PTX to diffuse out and induce cell death. Therefore, this clay-based Pickering nanoemulsion as a nanovehicle could realize the synergy of chemo- and photothermal therapy.

A new strategy to enhance molecular sonosensitivity is disclosed via tuning molecular assembly behavior, achieving highly efficient sonodynamic therapy of septic arthritis in a rat model.

Gold nanoclusters (AuNCs), with customized structures and diverse optical properties, are promising optical materials. Constructing composite systems by the assembly and incorporation of AuNCs can utilize their optical properties to achieve diagnostic and therapeutic applications in the biological field. Therefore, the exploration of the assembly behaviors of AuNCs and the enhancement of their performance has attracted widespread interest. In this review, we introduce multiple interactions and assembly modes that are prevalent in nanocomposites and microcomposites based on AuNCs. Then, the functions of AuNC composites for bioapplications are demonstrated in detail. These composite systems have inherited and enhanced the inherent optical performances of the AuNCs to meet diverse requirements for biological sensing and optical treatments. Finally, we discuss the prospects of AuNC composites and highlight the challenges and opportunities in biomedical applications.

Pt^II based organometallic photosensitizers (PSs) have emerged as novel potent photodynamic inactivation (PDI) reagents through their enhanced intersystem crossing (ISC) processes. Currently, few Pt^II PSs have been investigated as antibacterial materials, with relatively poor performances reported and with structure‐activity relationships not well described. Herein, a pair of configurational isomers are reported of Bis‐BODIPY (4,4‐difluoro‐boradizaindacene) embedded Pt^II PSs. The cis‐isomer (cis‐BBP) displayed enhanced ¹O₂ generation and better bacterial membrane anchoring capability as compared to the trans‐isomer (trans‐BBP). The effective PDI concentrations (efficiency > 99.9%) for cis‐BBP in Acinetobacter baumannii (multi‐drug resistant (MDR)) and Staphylococcus aureus are 400 nM (12 J cm⁻²) and 100 nM (18 J cm⁻²), respectively; corresponding concentrations and light doses for trans‐BBP in the two bacteria are 2.50 µM (30 J cm⁻²) and 1.50 µM (18 J cm⁻²), respectively. The 50% and 90% minimum inhibitory concentration (MIC₅₀ and MIC₉₀) ratio of trans‐BBP to cis‐BBP is 22.22 and 24.02 in A. baumannii (MDR); 21.29 and 22.36 in methicillin resistant S. aureus (MRSA), respectively. Furthermore, cis‐BBP displays superior in vivo antibacterial performance, with acceptable dark and photoinduced cytotoxicity. These results demonstrate cis‐BBP is a robust light‐assisted antibacterial reagent at sub‐micromolecular concentrations. More importantly, configuration of Pt^II PSs should be an important issue to be considered in further PDI reagents design.