A Supramolecular Naphthalene Diimide Radical Anion with Efficient NIR-II Photothermal Conversion for E. coli-Responsive Photothermal Therapy

We report a supramolecular naphthalene diimide (NDI) radical anion with efficient NIR-II photothermal conversion for E. coli-responsive photothermal therapy. The supramolecular radical anion (NDI-2CB[7])⋅⁻, which is obtained from the E. coli-induced in situ reduction of NDI-2CB[7] neutral complex, formed by the host–guest interaction between an NDI derivative and cucurbit[7]uril (CB[7]), exhibits unexpectedly strong NIR-II absorption and remarkable photothermal conversion capacity in aqueous solution. The NIR-II absorption is caused by the self-assembly of NDI radical anions to form supramolecular dimer radicals in aqueous solution, which is supported by theoretically predicted spectra. The (NDI-2CB[7])⋅⁻ demonstrates excellent NIR-II photothermal antimicrobial activity (>99 %). This work provides a new approach for constructing NIR-II photothermal agents and non-contact treatments for bacterial infections.     

Liquid Metal as Bioinspired and Unusual Modulator in Bioorthogonal Catalysis for Tumor Inhibition Therapy

Bioorthogonal catalysis mediated by Pd-based transition metal catalysts has sparked increasing interest in combating diseases. However, the catalytic and therapeutic efficiency of current Pd⁰ catalysts is unsatisfactory. Herein, inspired by the concept that ligands around metal sites could enable enzymes to catalyze astonishing reactions by changing their electronic environment, a LM-Pd catalyst with liquid metal (LM) as an unusual modulator has been designed to realize efficient bioorthogonal catalysis for tumor inhibition. The LM matrix can serve as a “ligand” to afford an electron-rich environment to stabilize the active Pd⁰ and promote nucleophilic turnover of the π-allylpalladium species to accelerate the uncaging process. Besides, the photothermal properties of LM can lead to the enhanced removal of tumor cells by photo-enhanced catalysis and photothermal effect. We believe that our work will broaden the application of LM and motivate the design of bioinspired bioorthogonal catalysts.     

Manipulating Host-Guest Charge Transfer of a Water-Soluble Double-Cavity Cyclophane for NIR-II Photothermal Therapy

Water-soluble small organic photothermal agents (PTAs) over NIR-II biowindow (1000–1350 nm) are highly desirable, but the rarity greatly limits their applications. Based on a water-soluble double-cavity cyclophane GBox-4⁴⁺ , we report a class of host–guest charge transfer (CT) complexes as structurally uniform PTAs for NIR-II photothermal therapy. As a result of its high electron-deficiency, GBox-4⁴⁺ can bind different electron-rich planar guests with a 1 : 2 host/guest stoichiometry to readily tune the CT absorption band that extends to the NIR-II region. When using a diaminofluorene guest substituted with an oligoethylene glycol chain, the host–guest system realized both good biocompatibility and enhanced photothermal conversion at 1064 nm, and was then exploited as a high-efficiency NIR-II PTA for cancer cell and bacterial ablation. This work broadens the potential applications of host–guest cyclophane systems and provides a new access to bio-friendly NIR-II photoabsorbers with well-defined structures.     

A DNA-Gated and Self-Protected Bioorthogonal Catalyst for Nanozyme-Assisted Safe Cancer Therapy

Transition metal catalysts (TMCs) mediated bioorthogonal uncaging catalysis has sparked increasing interest in prodrug activation. However, due to their “always-on” catalytic activity as well as the complex and catalytic-detrimental intracellular environment, the biosafety and therapeutic efficiency of TMCs are unsatisfactory. Herein, a DNA-gated and self-protected bioorthogonal catalyst has been designed by modifying nanozyme-Pd⁰ with highly programmable nucleic acid (DNA) molecules to achieve efficient intracellular drug synthesis for cancer therapy. Monolayer DNA molecules could endow the catalyst with targeting and perform as a gatekeeper to achieve selective prodrug activation within cancer cells. Meanwhile, the prepared graphitic nitrogen-doped carbon nanozyme with glutathione peroxidase (GPx) and catalase (CAT)-like activities could improve the catalytic-detrimental intracellular environment to prevent the catalyst from being inactivated and sensitize the subsequent chemotherapy. Overall, we believe that our work will promote the development of secure and efficient bioorthogonal catalytic systems and provide new insights into novel antineoplastic platforms.     

Self-enhanced photothermal-chemodynamic antibacterial agents for synergistic anti-infective therapy

Cu_2-xS nanostructures have been intensively studied as outstanding chemodynamic therapy (CDT) and good photothermal therapy (PTT) antibacterial agents due to their highly efficient Cu(Ⅰ)-initiated Fenton-like catalytic activity and good photothermal conversion property. However, they still suffer from shortage of Cu(Ⅰ) supply in the long-term and comparatively low inherent photothermal conversion efficiency. Herein, we constructed a self-enhanced synergistic PTT/CDT nanoplatform (Cu_1.94S@MPN) by coating Cu_1.94S nanoparticles with Fe(Ⅲ)/tannic acid based metal-polyphenol networks (MPN). Activated by the acidic bacterial infection microenvironment, Cu_1.94S@MPN could be decomposed to continuously release Cu(Ⅱ), Fe(Ⅲ) ions and tannic acid. As the result of tannic acid-involved Cu and Fe redox cycling, Cu(Ⅰ)/Fe(Ⅱ)-rich CDT could be achieved through the highly accelerated catalytic Fenton/Fenton-like reactions. More importantly, experimental results demonstrated that Cu_1.94S@MPN exhibited both excellent photothermal antibacterial and photothermal-enhanced CDT properties to eradicate bacteria in vitro and in vivo. Overall, this novel nanotherapeutics has great potential to become a clinic candidate for anti-infective therapy in future.     

Peptide-mediated Aqueous Synthesis of NIR-II Emitting Ag2S Quantum Dots for Rapid Photocatalytic Bacteria Disinfection

Pathogenic microorganisms in the environment are a great threat to global human health. The development of disinfection method with rapid and effective antibacterial properties is urgently needed. In this study, a biomimetic silver binding peptide AgBP2 was introduced to develop a facile synthesis of biocompatible Ag₂S quantum dots (QDs). The AgBP2 capped Ag₂S QDs exhibited excellent fluorescent emission in the second near-infrared (NIR-II) window, with physical stability and photostability in the aqueous phase. Under 808 nm NIR laser irradiation, AgBP2-Ag₂S QDs can serve not only as a photothermal agent to realize NIR photothermal conversion but also as a photocatalyst to generate reactive oxygen species (ROS). The obtained AgBP2-Ag₂S QDs achieved a highly effective disinfection efficacy of 99.06 % against Escherichia coli within 25 min of NIR irradiation, which was ascribed to the synergistic effects of photogenerated ROS during photocatalysis and hyperthermia. Our work demonstrated a promising strategy for efficient bacterial disinfection.     

Polyoxometalate‐Mediated One‐Pot Synthesis of Pd Nanocrystals with Controlled Morphologies for Efficient Chemical and Electrochemical Catalysis

Polyoxometalates (POMs), as inorganic ligands, can endow metal nanocrystals (NCs) with unique reactivities on account of their characteristic redox properties. In the present work, we present a facile POM‐mediated one‐pot aqueous synthesis method for the production of single‐crystalline Pd NCs with controlled shapes and sizes. The POMs could function as both reducing and stabilizing agents in the formation of NCs, and thus gave a fine control over the nucleation and growth kinetics of NCs. The prepared POM‐stabilized Pd NCs exhibited excellent catalytic activity and stability for electrocatalytic (formic acid oxidation) and catalytic (Suzuki coupling) reactions compared to Pd NCs prepared without the POMs. This shows that the POMs play a pivotal role in determining the catalytic performance, as well as the growth, of NCs. We envision that the present approach can offer a convenient way to develop efficient NC‐based catalyst systems.     

Structural and process controls of AIEgens for NIR-II theranostics

Aggregation-induced emission (AIE) is a cutting-edge fluorescence technology, giving highly-efficient solid-state photoluminescence. Particularly, AIE luminogens (AIEgens) with emission in the range of second near-infrared window (NIR-II, 1000–1700 nm) have displayed salient advantages for biomedical imaging and therapy. However, the molecular design strategy and underlying mechanism for regulating the balance between fluorescence (radiative pathway) and photothermal effect (non-radiative pathway) in these narrow bandgap materials remain obscure. In this review, we outline the latest achievements in the molecular guidelines and photophysical process control for developing highly efficient NIR-II emitters or photothermal agents with aggregation-induced emission (AIE) attributes. We provide insights to optimize fluorescence efficiency by regulating multi-hierarchical structures from single molecules (flexibilization) to molecular aggregates (rigidification). We also discuss the crucial role of intramolecular motions in molecular aggregates for balancing the functions of fluorescence imaging and photothermal therapy. The superiority of the NIR-II region is demonstrated by fluorescence/photoacoustic imaging of blood vessels and the brain as well as photothermal ablation of the tumor. Finally, a summary of the challenges and perspectives of NIR-II AIEgens for in vivo theranostics is given.

Structural and process controls of NIR-II AIEgens realize manipulating of radiative (R) and nonradiative (NR) decay for precise theranostics.     

Neuroprotective Bioorthogonal Catalysis in Mitochondria Using Protein-Integrated Hydrogen-Bonded Organic Frameworks

Mitochondria-targeted bioorthogonal catalysis holds promise for controlling cell function precisely, yet achieving selective and efficient chemical reactions within organelles is challenging. In this study, we introduce a new strategy using protein-integrated hydrogen-bonded organic frameworks (HOFs) to enable synergistic bioorthogonal chemical catalysis and enzymatic catalysis within mitochondria. Utilizing catalytically active tris(4,4′-dicarboxylicacid-2,2′-bipyridyl) ruthenium(II) to self-assemble with [1,1′-biphenyl]-4,4′-biscarboximidamide, we synthesized nanoscale RuB-HOFs that exhibit high photocatalytic reduction activity. Notably, RuB-HOFs efficiently enter cells and preferentially localize to mitochondria, where they facilitate bioorthogonal photoreduction reactions. Moreover, we show that RuB-HOFs encapsulating catalase can produce hydrogen sulfide (H₂S) in mitochondria through photocatalytic reduction of pro-H₂S and degrade hydrogen peroxide through enzymatic catalysis simultaneously, offering a significant neuroprotective effect against oxidative stress. Our findings not only introduce a versatile chemical toolset for mitochondria-targeted bioorthogonal catalysis for prodrug activation but also pave the way for potential therapeutic applications in treating diseases related to cellular oxidative stress.     

Cavity-Directed Synthesis of Labile Polyoxometalates for Catalysis in Confined Spaces

The artificial microenvironments inside coordination cages have gained significant attention for performing enzyme-like catalytic reactions by facilitating the formation of labile and complex molecules through a “ship-in-a-bottle” approach. Despite many fascinating examples, this approach remains scarcely explored in the context of synthesizing metallic clusters such as polyoxometalates (POMs). The development of innovative approaches to control and influence the speciation of POMs in aqueous solutions would greatly advance their applicability and could ultimately lead to the formation of elusive clusters that cannot be synthesized by using traditional methods. In this study, we employ host–guest stabilization within a coordination cage to enable a novel cavity-directed synthesis of labile POMs in aqueous solutions under mild conditions. The elusive Lindqvist [M₆O₁₉]²⁻ (M=Mo or W) POMs were successfully synthesized at room temperature via the condensation of molybdate or tungstate building blocks within the confined cavity of a robust and water-soluble Pt₆L₄(NO₃)₁₂ coordination cage. Importantly, the encapsulation of these POMs enhances their stability in water, rendering them efficient catalysts for environmentally friendly and selective sulfoxidation reactions using H₂O₂ as a green oxidant in a pure aqueous medium. The approach developed in this paper offers a means to synthesize and stabilize the otherwise unstable metal-oxo clusters in water, which can broaden the scope of their applications.     

The First Study on the Reactivity of Water Vapor in Metal–Organic Frameworks with Platinum Nanocrystals

We first studied the reactivity of H₂O vapor in metal–organic frameworks (MOFs) with Pt nanocrystals (NCs) through the water–gas shift (WGS) reaction. A water‐stable MOF, UiO‐66, serves as a highly effective support material for the WGS reaction compared with ZrO₂. The origin of the high catalytic performance was investigated using in situ IR spectroscopy. In addition, from a comparison of the catalytic activities of Pt on UiO‐66, where Pt NCs are located on the surface of UiO‐66 and Pt@UiO‐66, where Pt NCs are coated with UiO‐66, we found that the competitive effects of H₂O condensation and diffusion in the UiO‐66 play important roles in the catalytic activity of Pt NCs. A thinner UiO‐66 coating further enhanced the WGS reaction activity of Pt NCs by minimizing the negative effect of slow H₂O diffusion in UiO‐66.     

Photothermal Oxidation of Cinnamyl Alcohol with Hydrogen Peroxide Catalyzed by Gold Nanoparticle/Antimony-Doped Tin Oxide Nanocrystals

Gold nanoparticles with different mean sizes were formed on antimony-doped tin oxide nanocrystals by the temperature-varied deposition-precipitation method (Au/ATO NCs). Au/ATO NCs possess strong absorption in the near-infrared region due to Drude excitation in addition to the localized surface plasmon resonance (LSPR) of AuNPs around 530 nm. Au/ATO NCs show thermally activated catalytic activity for the oxidation of cinnamyl alcohol to cinnamaldehyde by hydrogen peroxide. The catalytic activity increases with a decrease in the mean Au particle size (d_Au) at 5.3 nm≤d_Au≤8.2 nm. Light irradiation (λ_ex >660 nm, ∼0.5 sun) of Au/ATO NCs increases the rate of reaction by more than twice with ∼95 % selectivity. Kinetic analyses indicated that the striking enhancement of the reaction stems from the rise in the temperature near the catalyst surface of ∼30 K due to the photothermal effect of the ATO NCs.     

NIR-II Light Powered Asymmetric Hydrogel Nanomotors for Enhanced Immunochemotherapy

Nanomotors are appealing drug carriers, and the strength of the propelling force is important for their motion capability. Though high motion efficiency has been achieved with 808 nm light driven Janus-structured noble metal nanomotors, the NIR-I light penetration depth and material biocompatibility limit their broad application. Herein, we develop a 1064 nm NIR-II light driven asymmetric hydrogel nanomotor (AHNM) with high motion capability and load it with doxorubicin for enhanced immunochemotherapy. Magnetic field assisted photopolymerization generates an asymmetric distribution of Fe₃O₄@Cu₉S₈ nanoparticles in the AHNM, producing self-thermophoresis as driving force under NIR-II irradiation. The AHNM is also functionalized with dopamine for the capture and retention of tumor-associated antigens to boost immune activation. The as-obtained NIR-II light driven AHNM has a high tumor tissue penetration capability and enhances immunochemotherapy, providing a promising strategy for cancer therapy.     

Unraveling the Impact of Gold(I)–Thiolate Motifs on the Aggregation-Induced Emission of Gold Nanoclusters

Aggregation-induced emission (AIE) provides an efficient strategy to synthesize highly luminescent metal nanoclusters (NCs), however, rational control of emission energy and intensity of metal NCs is still challenging. This communication reveals the impact of surface Au^I-thiolate motifs on the AIE properties of Au NCs, by employing a series of water-soluble glutathione (GSH)-coordinated Au complexes and NCs as a model ([Au₁₀SR₁₀], [Au₁₅SR₁₃], [Au₁₈SR₁₄], and [Au₂₅SR₁₈]⁻, SR=thiolate ligand). Spectroscopic investigations show that the emission wavelength of Au NCs is adjustable from visible to the near-infrared II (NIR-II) region by controlling the length of the Au^I-SR motifs on the NC surface. Decreasing the length of Au^I-SR motifs also changes the origin of cluster luminescence from AIE-type phosphorescence to Au⁰-core-dictated fluorescence. This effect becomes more prominent when the degree of aggregation of Au NCs increases in solution.     

Ag2S nanoparticles as an emerging single-component theranostic agent

Last two decades, with the rapid changes and development of nanotechnology and biological materials, diverse multi-functional nanomaterials emerging, which offers a novel way to treat and diagnose diseases, and therefore spawned the new biomedical technology of theranostics, which integrates the treatment and diagnosis or monitoring of diseases into one. Ag₂S as a bio-nanomaterial with low biotoxicity has attracted more and more attention due to its good photoluminescence properties and fluorescence imaging of small animals in the second near-infrared region (NIR-II). Meanwhile, Ag₂S has the ability to absorb near-infrared light strongly because of its local surface plasma resonance (LSPR) effect and had become a kind of photothermal converters with good photothermal conversion efficiency. More interestingly, both photothermal effect and fluorescence characteristics of Ag₂S nanoparticles (NPs) are closely related to their particle sizes. However, the relationship between photothermal effect and fluorescence characteristics of Ag₂S NPs and their sizes has not been reviewed so far. Herein, the synthesis methods and influencing factors of synthesize Ag₂S NPs with different sizes were compared firstly, and then the photothermal effect and fluorescence characteristics of Ag₂S NPs with different sizes were summarized. Finally, the possibilities and challenges of using Ag₂S NPs to construct theranostic agent were discussed in the end.     

Gas-Mediated Tumor Energy Remodeling for Sensitizing Mild Photothermal Therapy

The metabolic reprogramming of tumors requires high levels of adenosine triphosphate (ATP) to maintain therapeutic resistance, posing a major challenge for photothermal therapy (PTT). Although raising the temperature helps in tumor ablation, it frequently leads to severe side effects. Therefore, improving the therapeutic response and promoting healing are critical considerations in the development of PTT. Here, we proposed a gas-mediated energy remodeling strategy to improve mild PTT efficacy while minimizing side effects. In the proof-of-concept study, a Food and Drug Administration (FDA)-approved drug-based hydrogen sulfide (H₂S) donor was developed to provide a sustained supply of H₂S to tumor sites, serving as an adjuvant to PTT. This approach proved to be highly effective in disrupting the mitochondrial respiratory chain, inhibiting ATP generation, and reducing the overexpression of heat shock protein 90 (HSP90), which ultimately amplified the therapeutic outcome. With the ability to reverse tumor thermotolerance, this strategy delivered a greatly potent antitumor response, achieving complete tumor ablation in a single treatment while minimizing harm to healthy tissues. Thus, it holds great promise to be a universal solution for overcoming the limitations of PTT and may serve as a valuable paradigm for the future clinical translation of photothermal nanoagents.     

Atomically Precise Defective Copper Nanocluster Catalysts for Highly Selective C−C Cross-Coupling Reactions

Point defects in nanoparticles have long been hypothesized to play an important role in governing the particle's electronic structure and physicochemical properties. However, single point defects in material systems usually exist with other heterogeneities, obscuring the chemical role of the effects. Herein, we report the synthesis of novel atomically precise, copper hydride nanoclusters (NCs), [Cu₂₈H₁₀(C₇H₇S)₁₈(TPP)₃] ( Cu₂₈ ; TPP: triphenylphosphine; C₇H₇S: o-thiocresol) with a defined defect in the gram scale via a one-pot reduction method. The Cu₂₈ acts as a highly selective catalyst for C−C cross-couplings. The work highlights the potential of defective NCs as model systems for investigating individual defects, correlating defects with physiochemical properties, and rationally designing new nanoparticle catalysts.     

Building multipurpose nano-toolkit by rationally decorating NIR-II fluorophore to meet the needs of tumor diagnosis and treatment

Phototheranostics have attracted tremendous attention in cancer diagnosis and treatment because of the noninvasiveness and promising effectiveness. Developing advanced phototheranostic agents with long emission wavelength, excellent biocompatibility, great tumor-targeting capability, and efficient therapeutic effect is highly desirable. However, the mutual constraint between imaging and therapeutic functions usually hinders their wide applications in biomedical field. To balance this contradiction, we herein rationally designed and synthesized three novel tumor-targeted NIR-II probes (QR-2PEG₃₂₁, QR-2PEG₁₀₀₀, and QR-2PEG₅₀₀₀) by conjugating three different chain lengths of PEG onto an integrin α_vβ₃-targeted NIR-II heptamethine cyanine fluorophore, respectively. In virtue of the essential amphiphilic characteristics of PEG polymers, these probes display various degree of aggregation in aqueous buffer accompanying with differential NIR-II imaging and photothermal (PTT) therapeutic performance. Both in vitro and in vivo results have demonstrated that probe QR-2PEG₅₀₀₀ has the best NIR-II imaging performance with prominent renal clearance, whereas QR-2PEG₃₂₁ possesses excellent photoacoustic signal as well as PTT effect, which undoubtedly provides a promising toolbox for tumor diagnosis and therapy. We thus envision that these synthesized probes have great potential to be explored as a toolkit for precise diagnosis and treatment of malignant tumors.     

Deep Desulfurization by Amphiphilic Lanthanide‐Containing Polyoxometalates in Ionic‐Liquid Emulsion Systems under Mild Conditions

Amphiphilic lanthanide‐containing polyoxometalates (POMs) were prepared by surfactant encapsulation. Investigation of these lanthanide‐containing POMs in oxidative desulfurization (ODS) showed that highly efficient deep desulfurization could be achieved in only 14 min with 100 % conversion of dibenzothiophene under mild conditions by using (DDA)₉LaW₁₀/[omim]PF₆ (DDA=dimethyldioctadecylammonium, omim=1‐octyl‐3‐methyl‐imidazolium) in the presence of H₂O₂. Furthermore, deep desulfurization proceeds smoothly in model oil with an S content as low as 50 ppm. A scaled‐up experiment in which the volume of model oil was increased from 5 to 1000 mL with S content of 1000 ppm indicated that about 99 % sulfur removal can be achieved in 40 mins in an ionic‐liquid emulsion system. To the best of our knowledge, the (DDA)₉LaW₁₀/[omim]PF₆ catalyst system with H₂O₂ as oxidant is one of the most efficient desulfurization systems reported so far.     

Coupling molecular rigidity and flexibility on fused backbones for NIR-II photothermal conversion

Great attention is being increasingly paid to photothermal conversion in the near-infrared (NIR)-II window (1000–1350 nm), where deeper tissue penetration is favored. To date, only a limited number of organic photothermal polymers and relevant theory have been exploited to direct the molecular design of polymers with highly efficient photothermal conversion, specifically in the NIR-II window. This work proposes a fused backbone structure locked via an intramolecular hydrogen bonding interaction and double bond, which favors molecular planarity and rigidity in the ground state and molecular flexibility in the excited state. Following this proposal, a particular class of NIR-II photothermal polymers are prepared. Their remarkable photothermal conversion efficiency is in good agreement with our strategy of coupling polymeric rigidity and flexibility, which accounts for the improved light absorption on going from the ground state to the excited state and nonradiative emission on going from the excited state to the ground state. It is envisioned that such a concept of coupling polymeric rigidity and flexibility will offer great inspiration for developing NIR-II photothermal polymers with the use of other chromophores.

Low bandgap and large deformation generally conflict each other. This work couples molecular rigidity and flexibility by intramolecular hydrogen bonds and double bonds to achieve NIR-II light absorption and reinforced internal conversion at the same time.