Pollen is a natural, renewable, and biodegradable microparticle that has demonstrated significant potential for application in the biomedical field in recent years. It features a natural core-shell structure, unique morphology, and uniform size. The sporopollenin outer layer of pollen provides exceptional chemical stability, biocompatibility, and ultraviolet-resistant. Moreover, the surface of pollen is abundant in functional groups, allowing facile chemical modification. Owing to these distinctive physicochemical properties and favorable biological characteristics, pollen has emerged as an ideal biomaterial platform. This review outlines recent advances in the biomedical applications of pollen. It introduces methods for defatting and gelation processing of pollen and systematically summarizes its applications in various fields, including drug carriers, microrobots/micromotors, biosensors, three-dimensional printing, photothermal therapy, hemostasis, biological scaffolds, and ultraviolet-resistant. This review provides a reference for broadening the application of pollen and offers insights into the utilization of natural resources.

Colorectal cancer (CRC) remains a lethal malignancy often showing limited response to conventional therapies and immunotherapy due to multiple immune evasion mechanisms and gut microbiota dysbiosis. Herein, a multifunctional nanosonosensitizer (DMV@HA) was engineered and encapsulated within an inulin (IN)-based prebiotic hydrogel to enable synergistic sonodynamic-immunotherapy and gut microbiota modulation. Dendritic large-pore mesoporous silica nanoparticles (DLMSNs) were employed as a carrier platform for in situ MnO2 deposition and loading verteporfin (Vp), followed by coating with hyaluronic acid (HA). Vp functions as both a sonosensitizer for sonodynamic therapy (SDT) and a PD-L1 inhibitor for immunotherapy. MnO2 serves as an oxygen generator to enhance SDT efficacy and as a Mn2+ source to activate the cGAS-STING signaling pathway. Encapsulation within an IN hydrogel provides gastrointestinal stability and enables colon-targeted delivery. Upon fermentation, IN modulates the gut microbiota and induces immune activation, accompanied by the release of DMV@HA. Through HA-mediated binding to the CD44 receptor, DMV@HA is selectively internalized by CRC cells, and subsequently exerts potent sonodynamic effects to induce tumor ablation under ultrasound irradiation. Vp and Mn2+, intracellularly released from DMV@HA, further cooperatively promote immunostimulation to suppress tumor recurrence. Overall, this study presents a synergistic strategy that combines SDT with multimodal immune activation for CRC treatment.

Bacteria-derived components hold great promise for cancer therapy owing to their versatile biological properties. We previously reported that Porphyromonas gingivalis cell walls (PgCW), rich in intrinsic µ-oxo bisheme ([Fe(III)PPIX]2O), can effectively mediate both sonodynamic therapy (SDT) and chemodynamic therapy (CDT). More recently, we identified PgCW’s inherent potential to trigger ferroptosis. However, its therapeutic efficacy is limited by the hypoxic tumor microenvironment (TME) and insufficient endogenous hydrogen peroxide (H2O2) required for catalytic reactions. Herein, a self-sufficient nanoreactor (DCP) was developed by depositing calcium peroxide (CaO2) within dendritic large-pore mesoporous silica nanoparticles (DLMSNs), followed by the electrostatic adsorption of PgCW. Under ultrasound irradiation, DCP combines SDT and CDT with continuous glutathione (GSH) depletion to trigger ferroptosis. In the acidic TME, the decomposition of CaO2 generates O2 to enhance PgCW-mediated SDT, supplies H2O2 for Fenton-like CDT, and releases Ca2+ to induce calcium overload. The abundant reactive oxygen species (ROS) from CaO2-supplemented SDT and CDT, together with GSH exhaustion, amplify ferroptosis, driving severe lipid peroxidation (LPO) and cell membrane rupture to release damage-associated molecular patterns (DAMPs) for primary tumor regression. Furthermore, intracellular calcium overload synergistically promotes this ferroptosis-mediated immunogenic cell death (ICD), which, combined with the innate adjuvanticity of PgCW, drives robust systemic immune activation to suppress distant tumors. In summary, this nanoreactor overcomes TME limitations through self-sufficient substrate supply and efficiently combines calcium overload with amplified ferroptosis to suppress the growth and metastasis of oral squamous cell carcinoma (OSCC). These findings suggest a potential strategy for precision cancer immunotherapy.

Oral squamous cell carcinoma (OSCC) is an aggressive tumor that metastasizes frequently and invades the maxillary or mandibular bone easily when adjacent to the jaw bone. Caused by tumor-induced osteoclasts activation, bone invasion could release various cytokines from bone matrix that further promote cancer progression, leading to a bone-associated tumor vicious cycle and poorer prognosis. Herein, two clinical used small molecular drugs, verteporfin (Vp) and tazemetostat (Taz), are repurposed for off-label application and cleverly self-assembled into nanomedicine for dual eradicating cancer cells and inhibiting bone destruction. Specifically, Vp can be used for sonodynamic activation-mediated localized tumor ablation and generation of tumor antigens to activate antitumor immune response. EZH2 inhibitor Taz can amplify the antitumor immune response and inhibit bone invasion, when combining roles of Taz in epigenetically regulating tumor immunogenicity elevation and osteoclast inhibition. Moreover, macrophage membrane is utilized to encapsulate the nanomedicine to facilitate targeted drug delivery to OSCC and RANKL scavenging for osteoclast inhibition, aiding the microenvironment multi-mechanistic remodeling for synergistic therapy. Enhanced therapeutic outcomes have benefited from the nanodecoys in vivo via the animal model of OSCC with mandible invasion. Collectively, these results highlight the attractive functions of macrophage membrane-cloaked nanomedicine for effective and safe treatment against OSCC.

Intestinal barrier dysfunction underlies inflammatory bowel disease (IBD) and is driven, in part, by pathological crosstalk between macrophages and neutrophils that sustains pro-inflammatory cytokine release and excessive formation of neutrophil extracellular trap (NET). In this study, an oral cascade-responsive nanomedicine, PLBD, was developed to co-deliver the prostaglandin D2 receptor agonist BW245C and the NET scavenger DNase I with precise spatiotemporal control and minimal off-target release. PLBD comprises mucus-penetrating, reactive oxygen species (ROS)-sensitive liposomes (LBD) formulated from DSPE-SeSe-PEG, which co-encapsulate BW245C and DNase I, and a microbiota-degradable pectin shell providing gastrointestinal protection. After oral administration, the pectin coating facilitates colonic accumulation and undergoes microbiota-mediated fermentation, whereas the exposed PEGylated liposomes penetrate the mucus barrier. In the ROS-rich inflammatory microenvironment, cleavage of the Se-Se linker triggers the synchronous release of payloads. Functionally, released BW245C facilitates a functional shift in macrophages toward an anti-inflammatory M2-like state while DNase I degrades dysregulated NETs, interrupting the inflammatory loop. In murine models of intestinal barrier dysfunction, PLBD restores epithelial barrier integrity, reduces bacterial translocation, rebalances gut microbiota, attenuates IBD and systemic inflammation. Together, this work validates macrophage-neutrophil crosstalk as a tractable therapeutic target and provide a safe, orally translatable biomaterials strategy for intestinal barrier repair.

BackgroundPeriodontitis is a chronic inflammatory disease characterized by excessive oxidative stress, persistent bacterial biofilms, and progressive destruction of periodontal tissues. Current clinical treatments primarily focus on controlling bacterial infection but often show limited long-term efficacy due to unresolved immune dysregulation. Therefore, therapeutic strategies that simultaneously target microbial biofilms and the pathological immune microenvironment are urgently needed. In this study, we developed an injectable dual-drug hydrogel incorporating curcumin (CUR) and glycyrrhizic acid (GL) for the treatment of periodontitis.MethodsCUR was dissolved in melted polyethylene glycol distearate and then dispersed in an aqueous medium to form micelles (CURM). Compared to CUR, CURM exhibited improved solubility and stability, thereby displaying greatly enhanced antioxidative, anti-inflammatory, and antibacterial activities. CURM were subsequently embedded within a hydrogel self-assembled from glycyrrhizic acid and polyvinyl alcohol (GLH) to form a dual-drug hydrogel system (CURM@GLH). Experimental periodontitis was established in mice to test their in vivo effects.ResultsOwing to the intrinsic anti-inflammatory and antioxidative properties of glycyrrhizic acid, the hydrogel exhibited combined effects in regulating immune dysregulation. The CURM@GLH effectively protected cells from oxidative damage, reduced intracellular reactive oxygen species levels, promoted macrophage polarization from the proinflammatory M1 phenotype toward the pro-regenerative M2 phenotype, and downregulated proinflammatory cytokine expression. In a ligature-induced rat model of periodontitis, local administration of the hydrogel significantly alleviated periodontal oxidative stress and inflammation and markedly reduced alveolar bone resorption.ConclusionsThis study presents an injectable dual-drug hydrogel, CURM@GLH, that integrates biofilm inhibition with immunomodulatory regulation, offering a promising host-directed therapeutic strategy for periodontitis. The proposed approach provides new insights into the design of multifunctional biomaterials for the treatment of chronic inflammatory diseases associated with biofilm persistence and immune imbalance.

A versatile bacterial cell wall (PgCW) extracted from Porphyromonas gingivalis exhibited POD-mimicking, SDT, CDT, and immunoadjuvant performances. PgCW was used to fabricate a nanomedicine for OSCC combination treatment.

Inflammatory bowel disease (IBD) management remains challenging due to the inadequate efficacy and systemic toxicity of conventional therapies. Herein, we developed an inulin hydrogel loaded with self-assembled nanoparticles of curcumin and glycyrrhizic acid (CURG@IN) for IBD treatment. CURG@IN exhibited remarkable gel characteristics and enzyme-responsive drug release behavior. In vitro, CURG@IN demonstrated potent antioxidant capabilities, effectively protecting cells from oxidative injury, facilitating wound healing of epithelial cells, and regulating macrophage polarization. Additionally, it exerted inhibitory effects on the NF-κB pathway, thereby reducing the production of inflammatory cytokines. In DSS-induced colitis mice, oral CURG@IN significantly ameliorated disease activity index and restored colonic histological architecture. Gut barrier integrity was reinforced through upregulation of tight junction proteins, while microbiota analysis revealed significant restoration of microbial homeostasis. Notably, no significant toxicity was observed during treatment. Collectively, this oral therapeutic strategy provides a multimechanistic approach combining anti-inflammatory, antioxidative, and microbiota-modulating effects for safe IBD therapy, with the potential for clinical application.

Gut microbiota imbalance-induced inflammatory response and oxidative stress are two of the main reasons causing ulcerative colitis (UC). Probiotics show potent modulating effects on microbiota imbalance and have been considered as an optimal substitute of antibiotics for preventing UC. However, the harsh environment of the gastrointestinal tract is not conducive to the survival and persistence of probiotics. Herein, we developed an efficient surface coating strategy to overcome the delivery challenges of probiotics and also endow them with multiple functions through layer-by-layer coating with tannic acid (TA)-Mg2+ and casein phosphopeptide (CPP) complexes. Saccharomyces boulardii (SB), one of yeasts that have been widely applied in the food and pharmaceutical field, was used as a model probiotic for assessing the synergistic effects of this coating strategy on preventing UC. Multi-functionalized probiotic thus prepared (called SB@TA-Mg2+@CPP) had significantly enhanced stability under the simulated gastric and intestinal fluid conditions, and also displayed vigorous cell viability and potent antioxidant activity. In the mouse model of dextran sulfate sodium (DSS)-induced colitis, SB@TA-Mg2+@CPP exhibited strong antioxidant and anti-inflammatory effects, remarkably increased the abundance and diversity of gut microbiota, and maintained gut barrier integrity. Meanwhile, SB@TA-Mg2+@CPP notably improved the adsorption of Mg2+, which also contributed to enhance the preventive effect against DSS-induced colitis. In summary, this study provides an efficient coating strategy to develop multi-functionalized probiotics for preventing UC.

Orthodontic treatment is frequently associated with the development of periodontal inflammation which may compromise dental stability and orthodontic efficacy. Consequently, the prevention of periodontal inflammation is crucial and indispensable. In this study, we report for the first time that oil bodies (OBs) extracted from grape seeds contain various bioactive compounds and therefore exhibit multifunctional properties in preventing periodontal inflammation, including antioxidative, antibacterial, anti-inflammatory, and bone metabolism regulatory activities. To enhance these functionalities, a multifunctional emulsion (OB@QCS) is developed by coating quaternary ammonium chitosan (QCS) onto the surfaces of grape seed OBs via electrostatic interaction. The presence of QCS endows OB@QCS with markedly stronger antibacterial activity than OBs, efficiently inhibiting the biofilm formation of periodontal pathogens. Furthermore, OB@QCS promotes the osteogenic differentiation of bone marrow mesenchymal stem cells through both direct and indirect mechanisms. In an animal model combining periodontal inflammation with orthodontic tooth movement, OB@QCS effectively prevents inflammation, enhances osteogenesis, and suppresses osteoclastogenesis, thereby alleviating alveolar bone resorption synergistically. In summary, this study not only develops a multifunctional emulsion but also offers a promising strategy for preventing periodontal inflammation during orthodontic treatment.

Wound healing is a dynamic and complex process involving hemostasis, inflammation, fibroblast proliferation, and tissue remodeling. This process is highly susceptible to bacterial infection, which often leads to impaired and delayed wound repair. While antibiotic therapy remains the primary clinical approach for treating bacteria-infected wounds, its widespread use poses a significant risk of developing bacterial resistance. Here, a novel drug-free hydrogel was fabricated using polysaccharides and humic acid (HU) to facilitate the healing of bacteria-infected wounds. Specifically, hyaluronic acid (HA) was modified via oxidation with sodium periodate, introducing aldehyde groups along its main chains. Pectin (PT) was grafted with amino groups on its side chains through an amidation reaction with ethylenediamine. HU, a natural organic compound with hemostatic, antioxidant, antibacterial, anti-inflammatory, and photothermal properties, was reduced using sodium borohydride to generate an increased number of phenolic hydroxyl and catechol groups. The resulting hydrogel, called HA-PT/HUOH, was prepared by integrating these three chemically modified biomaterials through dynamic Schiff base cross-linking and hydrogen bonding. The HA-PT/HUOH hydrogel showed excellent injectability, strong bioadhesiveness, rapid self-healing capabilities, and potent photothermal performance. Both in vitro and in vivo studies demonstrated that HA-PT/HUOH significantly accelerated the healing of bacteria-infected wounds by modulating the entire wound-healing process. This included enhancing hemostasis, bacteriostasis, antioxidation, anti-inflammatory responses, fibroblast proliferation, and tissue remodeling. In summary, this multifunctional drug-free hydrogel presents a highly promising solution as a wound dressing for clinical application.

Bacterial cancer therapy recently has been attracting more and more attention because of its multiple functions to fight cancer. Porphyromonas gingivalis (Pg), a Gram-negative pathogenic bacterium, acquires protoporphyrin IX (PpIX) and iron from heme and synthesizes abundant µ-oxo bisheme on its cell walls (CWs). For the first time, it is found that the CWs extracted from Pg has intrinsic peroxidase (POD)-mimicking and sonodynamic activities owing to the presence of µ-oxo bisheme. In this study, the CWs of Pg are nanofabricated to form the CW vesicles (CWV) containing a large amount of lipopolysaccharide (LPS) and further encapsulated doxorubicin (DOX) to prepare DOX-loaded CWV (DOX@CWV), hoping to eradicate cancer by combining sonodynamic therapy (SDT), chemotherapy, and bacterial immunotherapy. The results confirmed that DOX@CWV can catalyze the conversion of H2O2 into O2 and consume the reduced glutathione (GSH), and thus greatly boost their own sonodynamic performance upon ultrasonic irradiation. Both in vitro and in vivo, DOX@CWV efficiently inhibited cancer growth by combining SDT and chemotherapy, and also exerted synergistic anticancer immune effects of bacterial immunotherapy and SDT. In summary, the findings not only contribute a promising bacterial therapeutic agent but also provide a combination strategy for clinical cancer treatment.

Aim or purpose: Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck region. Although sonodynamic therapy (SDT) with ultrasound shows promise as a treatment approach, existing sonosensitizers frequently present challenges including toxic side effects and complicated preparation processes. This study presents a safer, more accessible alternative by introducing a novel, naturally-derived therapeutic agent. Materials and methods: We report the first extraction of curcumin-enriched microemulsion (CM) from turmeric, which significantly improve curcumin's solubility and bioavailability. These microemulsion were modified with cRGD peptides through click chemistry, creating microemulsion-peptide conjugates (CMC) that can target tumor blood vessels. Results: Due to its high curcumin solubility and enhanced absorption by endothelial cells, CMC exhibited excellent sonodynamic performance and significantly inhibited the migration and tube formation ability of endothelial cells. Under low-frequency ultrasound, CMC reduce to nano-size, allowing better uptake by tumor cells and enhancing curcumin's ability to promote tumor Cell apoptosis. In OSCC mouse models, CMC effectively target tumors and, when combined with ultrasound, significantly disrupt tumor blood vessels and induce tumor cell death. Conclusions: This study develops a natural, curcumin-rich emulsion that works through dual sonodynamic mechanisms, offering a new approach for OSCC treatment. It maximizes the therapeutic potential of curcumin as both a natural sonosensitizer and anti-tumor agent, providing a promising strategy for treating oral squamous cell carcinoma with reduced side effects and improved efficacy compared to conventional methods

Periodontitis is a chronic inflammatory disease that leads to periodontal attachment loss and is a major cause of adult tooth loss. Current treatment of mechanical debridement is often ineffective in deep periodontal pockets, and antibiotic adjuncts carry the risk of bacterial resistance. Octyl gallate (OG), a natural plant-derived compound with antibacterial and antioxidant properties, is limited by poor water solubility and stability. This study aimed to develop a sustained-release ointment (OG-Ointment) using Pluronic F127 and ethylcellulose to enhance the delivery and efficacy of OG. The formulated OG-Ointment demonstrated excellent rheological properties, sustained drug release, and potent ABTS+ radical scavenging. In vitro, it enhanced bacterial membrane permeability, inhibited P. gingivalis growth, and reduced ROS in macrophages. In a rat periodontitis model, OG-Ointment significantly reduced alveolar bone resorption, decreased ROS and inflammatory cytokines, and exhibited good biocompatibility. These findings suggest that OG-Ointment is a promising non-antibiotic adjunctive therapy for periodontitis, combining dual antioxidant and antibacterial functions with sustained release.

Aim or purpose: Periodontitis is a chronic inflammatory disorder characterized by aggravated oxidative stress and progressive tissue destruction, as results of local immune dysregulation. Current clinical treatments focus on controlling bacterial infections, but remains limited efficacy due to persistent immune dysregulation. Here, we developed an injectable micelle-hydrogel hybrid containing curcumin (CUR) and glycyrrhizic acid (GL), named as CURM@GLH, for periodontitis treatment by reducing oxidative stress and regulating immune microenvironment. Materials and methods: CUR was dissolved in melted polyethylene glycol distearate and then dispersed in aqueous medium to form micelles (CURM). Compared to CUR, CURM had improved solubility and stability, thus displayed greatly promoted antioxidative, anti-inflammatory, antibacterial, and anti-biofilm activities. CURM were encapsulated into a hydrogel self-assembled from GL and polyvinyl alcohol to obtain CURM@GLH. Experimental periodontitis were established in mouse to test their in vivo effects. Results: Owing to the anti-inflammatory property of GL, CURM@GLH exerted the synergistic effects of CURM and GLH against immune dysregulation. CURM@GLH significantly repolarized macrophages from M1 to M2 phenotype, down-regulated the expression levels of pro-inflammatory cytokines, and meanwhile up-regulated the expression levels of anti-inflammatory cytokines. The ligature-induced periodontitis model in mouse showed that, CURM@GLH effectively alleviated oxidative stress and inflammation in periodontal tissues, thereby deminished alveolar bone resorption. Conclusions: The injectable CURM@GLH micelle-hydrogel hybrid combines curcumin and glycyrrhizic acid, synergistically alleviating oxidative stress and reprogramming immunity. It effectively inhibits inflammation and alveolar bone loss in periodontitis, demonstrating a potent dual-drug therapeutic strategy.

Salivary adenoid cystic carcinoma (SACC) is one of the most common salivary gland malignancies. Current clinical therapies have limitations and cannot efficiently prevent the SACC development and metastasis. Hematogenous and neural spread are the two major routes of SACC metastasis. In this study, a precise and intelligent nanomedicine, RCDT, is designed to combine antivascular photodynamic therapy and neuroinhibitory chemotherapy against SACC. A tumor vessel-targeted and reactive oxygen species (ROS)-responsive photosensitizer (RC) is synthesized by linking cRGD to chlorin e6 (Ce6) via a bridge between the poly(ethylene glycol) and diselenide bonds. A neural-targeted and pH-responsive cytotoxic prodrug (DT) is synthesized by conjugating doxorubicin (DOX) with Tet1, a neural-targeting peptide, via an acidic-cleavable hydrazone bond. RC and DT are assembled to form RCDT via hydrophobic interactions, thereby shielding Tet1. Under the guidance of cRGD and the photodynamic action of Ce6, RCDT can precisely disrupt the tumor vasculature and simultaneously disintegrate to expose Tet1 by rupturing the diselenide bond. Guided by Tet1, disintegrated RCDT can be specifically internalized into neurons and release DOX to exert neuroinhibitory effects by cleaving the hydrazone bond. Using these stepwise dual-targeting and dual-responsive strategies, RCDT can efficiently suppress the growth and metastasis of SACC.

Melittin (Mel) is considered a promising candidate drug for the treatment of triple negative breast cancer (TNBC) due to its various antitumor effects.

Pathogenic bacteria are closely associated with the occurrence, development and metastasis of oral squamous cell carcinoma (OSCC). Antibacterial therapy has been considered an enhancement strategy to suppress bacteria-associated tumors and promote anti-tumor immune responses. Herein, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for the in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis (Pg), one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, composed of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820, was prepared using a simple dissolve-dry-swell solvent exchange method. Upon 808 nm laser irradiation, PNIPAM/DL@TIR exerted photothermal effects to ablate Pg-colonized OSCC and generate dual tumor and bacterial antigens. Owing to its large number of catechol groups, PNIPAM/DL@TIR efficiently captured these antigens to form an in situ antigen repository, thereby eliciting robust and durable antitumor immune responses. Proteomic analysis revealed that the captured antigens comprised both tumor neoantigens and bacterial antigens. The catechol groups endowed PNIPAM/DL@TIR with antioxidant activity, which was also conducive to stimulating antitumor immunity. Altogether, this study develops an injectable adhesive hydrogel and provides a combination strategy for treating bacteria-associated OSCC. Statement of significance In this study, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis, one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, which consists of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820 exhibited outstanding photothermal performance. Owing to the presence of catechol groups, PNIPAM/DL@TIR has good bioadhesive properties and can capture protein antigens to form in situ antigen repository, thus initiating robust and long-term antitumor immune responses. In addition, PNIPAM/DL@TIR exhibited strong antioxidant activity that is favorable for promoting antitumor immunity. In the mouse model of OSCC with bacterial infection, PNIPAM/DL@TIR not only ablated the primary tumors upon NIR laser irradiation, but also induced tumor and bacterial vaccination in situ to suppress distant tumors and lung metastasis.

Single-atom nanozymes (SAzymes) have made significant strides in antibacterial treatment but fall short as natural enzyme and drug replacements due to limited catalytic performance. Here, a rational strategy is presented for incorporating spatially axial boron (B) ligands to effectively modulate the local coordination environment of planar Fe & horbar;N4 motifs (Fe & horbar;B/N & horbar;C SAzymes). With electronic modulation, the Fe & horbar;B/N & horbar;C SAzymes exhibit significantly enhanced oxidase-, peroxidase-, and catalase-like activities. Theoretical calculations highlight that the spatially axial B ligands effectively adjust the charge distribution around the planar Fe & horbar;N4 active center, which facilitates the heterolysis of H2O2 and the desorption of O2, resulting in accelerated H2O2 decomposition. Furthermore, the intrinsic photothermal effect of Fe & horbar;B/N & horbar;C SAzymes enhances multienzyme-like activities, rapidly generating abundant reactive oxygen species (ROS), and achieving chemodynamic/photothermal synergistic therapy for impressive disinfection against periodontal-related pathogenic bacteria. These findings offer a distinctive viewpoint for optimizing the local coordination environment of SAzymes with axial ligand to enhance their catalytic performance and effectiveness in periodontitis therapy. A rational strategy is developed to enhance the multienzymatic performance of SAzymes by spatially axial boron ligands, which effectively modulate the local coordination environment of planar Fe & horbar;N4 motifs (Fe & horbar;B/N & horbar;C). The photothermal effect of Fe & horbar;B/N & horbar;C SAzymes accelerates the multi-enzyme-like activities for the rapid generation of abundant reactive oxygen species (ROS) and O2, showcasing impressive disinfection efficacy against periodontal-related pathogenic bacteria. image