ROS Generation Ability Research Articles

A nitroreductase-responsive fluorescence turn-on photosensitizer for lysosomes imaging and photodynamic therapy

Nitroreductase (NTR) is a frequently used biomarker for the assessment of hypoxia level in tumors. As one of the main sources of enzymes, the dysfunction of lysosomes typically leads to various diseases. In this study, an NTR-triggered lysosome-targeting probe, M-TPE-P, was designed based on a tetraphenylethylene core. DFT calculation indicated that the probe possessed a narrow singlet–triplet energy gap (ΔEST), rendering it an efficient photosensitizer. The docking affinity of M-TPE-P to NTR revealed a strong structural match between them. Photophysical properties demonstrated that the probe exhibited high selectivity and sensitivity in a broad pH rang for detecting NTR with kcat/Km as 2.18 × 104 M−1 s−1. The detection limit was determined to be 53.6 ng/mL in 80 % PBS/DMSO solution. Cell imaging studies showed the probe could trace intracellular NTR behavior with green fluorescence. The colocalization analysis indicated its excellent lysosome-targeting specificity. In addition, the probe exhibited effective ROS generation ability and significant PDT effect after NIR irradiation, positioning it as a promising photosensitizer for cancer treatment.

WITHDRAWN: A nitroreductase-responsive fluorescence turn-on photosensitizer for lysosomes imaging and photodynamic therapy

Nitroreductase (NTR) is a frequently used biomarker for the assessment of hypoxia level in tumors. As one of the main sources of enzymes, the dysfunction of lysosomes typically leads to various diseases. In this study, an NTR-triggered lysosome-targeting probe, M-TPE-P, was designed based on a tetraphenylethylene core. DFT calculation indicated that the probe possessed a narrow singlet–triplet energy gap (ΔEST), rendering it an efficient photosensitizer. The docking affinity of M-TPE-P to NTR revealed a strong structural match between them. Photophysical properties demonstrated that the probe exhibited high selectivity and sensitivity in a broad pH rang for detecting NTR. The detection limit was determined to be 53.6 ng/mL in 80% PBS/DMSO solution. Cell imaging studies showed the probe could trace intracellular NTR behavior with green fluorescence. The colocalization analysis indicated its excellent lysosome-targeting specificity, with a Pearson correlation coefficient of 0.97. In addition, the probe exhibited effective ROS generation ability and a significant PDT effect after NIR irradiation, positioning it as a promising photosensitizer for cancer treatment.

Sulfur oxidation states manipulate excited state electronic configurations for constructing highly efficient organic type I photosensitizers.

The multiple relaxation processes of excited states are a bridge connecting molecular structures and properties, providing enormous application potential for organic luminogens. However, a systematic understanding and manipulation of the relationship between the molecular structure, excited state relaxation processes, and properties of organic luminogens is still lacking. Herein, we report a strategy for manipulating excited state electronic configurations through the regulation of the sulfur oxidation state to construct eminent organic type I PSs. Combined with the experimental results and theoretical calculations, we have successfully revealed the decisive role of high sulfur oxidation states in promoting ROS production capacity. Impressively, a higher sulfur oxidation state can reduce the singlet-triplet energy gap (ΔE ST), increase the matching degree of transition configurations, promote the changes of the excited state electronic configurations, and boost the effective ISC proportion by enhancing intramolecular interactions. Therefore, DBTS2O with the highest sulfur oxidation state exhibits the strongest type I ROS generation ability. Additionally, guided by our strategy, a water-soluble PS (2OA) is designed and synthesized, showing selective imaging capacity and photokilling ability against Gram-positive bacteria. This study broadens the horizons for both molecular design and mechanism study of high-performance organic type I PSs.

Outstanding ROS generation ability and the mechanism of MXene quantum dots

Under 365 nm UV irradiation, MXene-derived MQDs (Ti3C2, Ti2C and V2C QDs) can efficiently generate diverse reactive oxygen species due to their unique band structure, high carrier separation, and superior electron transfer.

A new magnetic heterogeneous catalyst for fast degradation of rhodamine B by peroxymonosulfate oxidation: Monodisperse-porous and Fe3O4 incorporated manganese oxide microspheres

A new synthetic method, “staged shape templating decomposition” suitable for transition or rare-earth metal oxide microspheres was developed for obtaining magnetic, uniform and porous manganese oxide (MagMnOx) microspheres. The microspheres 4.7 μm in size were obtained with a specific surface area of 45.5 m2 g−1. Fe3O4, Mn5O8, MnO2 and Mn2O3 phases were shown by X-ray diffraction spectroscopy. Mn2+, Mn3+ and Mn4+ states were observed on the surface by X-ray photoelectron spectroscopy. Catalase-like and oxidase-like activities of MagMnOx microspheres were explained by coexistence of Mn and Fe crystallites in a mesoporous structure with a sufficiently large surface area and a particle interior with large mesopores facilitating substrate diffusion. The maximum substate consumption rates for catalase-like and peroxidase-like activities were determined as 15.6 mM/min and 20.3 μM/min, respectively. By considering their ROS generation ability, MagMnOx microspheres were evaluated as a heterogeneous catalyst for rhodamine B (Rh B) removal via peroxymonosulfate (PMS) activation. Rh B was removed in the periods shorter than 15 min via chemical degradation with a limited physical adsorption. Superoxide anion (O2−●) and singlet oxygen (1O2●) radicals generated by MagMnOx-PMS system were responsible for degradation of Rh B. The highest apparent first order rate constant for Rh B degradation was calculated as 0.5771 min−1. The apparent first order rate constant increased with increasing MagMnOx and PMS concentrations and decreasing initial Rh B concentration. Rh B was almost completely removed in each of five recycling runs and only lower than 1.5 % w/w of Fe and Mn contents of MagMnOx microspheres were leached over five recycling runs. The catalyst with large particle size, resistant to agglomeration exhibited high removal rate, low dye adsorption, high magnetization, and high reusability for Rh B removal via peroxymonosulfate activation.

D‐type neuropeptide decorated AIEgen/RENP hybrid nanoprobes with light‐driven ROS generation ability for NIR‐II fluorescence imaging‐guided through‐skull photodynamic therapy of gliomas

AbstractGlioma is one of the most common malignant tumors of the central nervous system, leading high mortality rates in human. Aggregation‐induced emission (AIE) photosensitizers‐based photodynamic therapy (PDT) has emerged as a promising therapeutic strategy for least‐invasive treatment of glioma, which involves local irradiation of the tumor using an external near‐infrared (NIR) laser. Unfortunately, most AIE photosensitizers suffered from poorly penetration of the visible light excitation, bad spatiotemporal resolution in deep tissues and low efficient blood‐brain barrier (BBB) crossing ability, which greatly limited the clinical practice of AIE photosensitizers for especially deep‐seated brain tumor treatment. In this work, we developed a multifunctional NIR‐driven theranostic agent through hybrid of AIE photosensitizers TIND with rare‐earth doping nanoparticles (RENPs) NaGdF4:Nd/Yb/Tm with up/down dual‐mode conversion luminescence. The theranostic agent was further decorated with D‐type neuropeptide DNPY for crossing BBB and targeting glioma. Under the 808‐nm light irradiation, the down‐conversion NIR‐II luminescence could indicate the position glioma and the upconversion NIR‐I luminescence could trigger the AIE photosensitizers producing reactive oxygen species to inhibit orthotopic glioma tumor growth in situ. These results demonstrate that the integration of D‐type neuropeptide, AIE photosensitizers and RENPs could be promising candidates for in vivo NIR‐II fluorescence image‐guided through‐skull PDT treatments of brain tumors.

An ultrasound-activated heterojunction as ROS generator given scaffolds sonodynamic antibacterial effect

Potassium niobate (KNbO3) with favorable biocompatibility presented a great potential in the sonodynamic therapy of implant-related infection due to its superior piezoelectric performance. However, the rapid electron-hole pair recombination weakened its sonodynamic therapy effect. In this work, Au@KNbO3 heterojunctions were synthesized by depositing Au nanoparticles on KNbO3, and then mixed with poly-l-lactic acid (PLLA) powder to prepare scaffold by laser additive manufacturing. Herein, Au with lower Fermi level acted as electron trap to capture the ultrasonic-excited electrons from KNbO3. Subsequently, Au formed Schottky barrier with KNbO3 to prevent electrons backflow. As a result, the electron-hole was expected to be separated. EIS curves indicated that Au@KNbO3 presented a smaller arc radius than that of KNbO3, confirming the electron-hole separation efficiency of Au@KNbO3 was enhanced. Following that, ROS generation ability of the scaffold was significantly strengthened. Antibacterial tests revealed that the generated ROS could not only trigger protein leakage by disrupting bacterial cell membranes, but also deplete glutathione to weaken the antioxidant defense of bacteria. As a consequence, the scaffold exhibited excellent antibacterial abilities of 92% and 90% against S. aureus and E. coli, respectively. Collectively, this work provided a promising countermeasure to fight the implant-related infection.

ROS induction within 4T1 breast cancer cells by CuS NPs as chemodynamic agent

Minimally invasive and highly precise cancer cell death is a goal, and nanoformulations that can respond to the unique TME hold promise. This article describes the development of a nanoparticles (NPs) for chemodynamic treatment (CDT) to combat the cancer. As a consequence, CuS NPs cores are used as Fenton-like catalysts, while Alginate (Alg) is used as a stabilizer and template for entrapping and stabilizing Cu NPs. Here, Alg coated CuS NPs (CuS@Alg NPs) was synthesized via a green and facile method. To promote biocompatibility, Alg is added to the system. The malignant cells are killed by generated toxic hydroxyl radicals (·OH) using CuS@Alg NPs as a Fenton-like process catalyst. The effectiveness of NPs was assessed by MTT assay, live/dead cells staining, and ROS generation within cancer cells. Results not only confirmed ROS generation ability of CuS@Alg NPs within cells, but also show the anticancer ability of them. By CDT, the created smart nanoscale system showed remarkable effectiveness for breast cancer suppression.

Synergistic antibacterial effect of multifunctional TiO2−X-based nanoplatform loading arginine and polydopamine for promoting infected wounds healing

The gas therapy of some endogenous signaling molecules to treat diseases has caused extensive research, among which NO gas has shown great potential in fighting infection with various pathogens, promoting wound healing, etc. Here, we propose a photothermal/photodynamic/NO synergistic antibacterial nanoplatform by loading L-arginine (LA) on mesoporous TiO2 and then encapsulating it with polydopamine. The obtained TiO2−x-LA@PDA nanocomposite possesses both the excellent photothermal effect and ROS generation ability of mesoporous TiO2, and the release of nitric oxide (NO) from L-arginine under near-infrared (NIR) light irradiation, while the sealing layer of PDA could induce NIR-triggered NO controlled release. In vitro antibacterial experiments confirmed that the synergistic effect of TiO2−x-LA@PDA nanocomposites has excellent antibacterial effects against Gram-negative and Gram-positive bacteria, while in vivo experiments showed that it has lower toxicity. It is worth noting that compared with the pure photothermal effect and ROS, the generated NO showed a better bactericidal effect, and NO had a better ability to promote wound healing. In conclusion, the developed TiO2−x-LA@PDA nanoplatform can be used as a nanoantibacterial agent, which can be further explored in the related biomedical field of photothermal activation of multimodal combined antibacterial therapy.

A hypochlorite-activated strategy for realizing fluorescence turn-on, type I and type II ROS-combined photodynamic tumor ablation

The combination of cancer cell-activated fluorescence and the advantages of both type I and type II photodynamic therapy (PDT) capabilities to achieve a synergistic therapeutic effect in a complex tumor environment is highly desirable. Herein, we report an approach by means of tumor intracellular hypochlorite (ClO−) to turn on fluorescence integrated with type I and II ROS generation for imaging-guided PDT. The resultant PTZSPy functions as a type II photosensitizer with mitochondria-targeting capability. In the presence of ClO−, PTZSPy is transformed into its oxidized counterpart SPTZSPy, turns on an orange-red fluorescence and triggers the type I ROS generation ability. Biological studies revealed that PTZSPy can accurately distinguishes tumor cells from normal cells, dynamically monitors the cell ablation process and be utilized for theranostics in MCF-7 tumor-bearing nude mice in vivo. This work provides an innovative strategy exploiting the highly abundant ClO− in tumor cells for the type I and II ROS two-pronged and imaging-guided PDT.

A novel photoswitchable AIE-active supramolecular photosensitizer with synergistic enhancement of ROS-generation ability constructed by a two-step sequential FRET process

An AIE-active supramolecular photosensitizer with excellent switchable ROS-generation ability is successfully fabricated in an aqueous environment based on a two-step sequential FRET process.

Ag-Doped Metal-Organic Frameworks' Heterostructure for Sonodynamic Therapy of Deep-Seated Cancer and Bacterial Infection.

Metal-organic frameworks (MOF) have attracted great potential in sonodynamic therapy (SDT) owing to large sonosensitizers' loading and fast reactive oxygen species' (ROS) diffusion; however, the low ligand-to-metal charge transfer efficiency sharply impairs the SDT effect. Herein, we report the design of MIL@Ag heterostructures with high electron-hole pairs separation efficiency and enhanced diverse ROS generation ability for deep-seated cancer treatment and bacterial infection. The MIL@Ag heterostructure is composed of Ti-based MOFs (named MIL), on which are in situ assembled silver nanoparticles (Ag NPs). The electrochemical experiments and density functional theory calculations verify that the introduction of Ag NPs can significantly improve the electron transfer efficiency and O2 adsorption capacity of MIL. Under ultrasound irradiation, the doped Ag NPs can trap the activated electrons from MIL to reduce surrounding O2 and produce superoxide radicals (•O2-), while the activated holes enable oxidizing H2O to produce hydroxyl radicals (•OH). Thus, they efficiently improve the therapeutic efficiency of SDT. MIL@Ag-PEG-mediated SDT implements A549 cancer cells' killing under a tissue barrier of 2 cm and eradicates the bacterial infection of Staphylococcus aureus, thus promoting wound healing. Therefore, MIL@Ag-PEG provides a promising strategy for augmenting SDT performance by rational heterostructure design of sonosensitizers.

An “all in one” strategy to boost antibacterial phototherapy via porphyrin and boron dipyrromethenes based covalent organic framework

Bacterial drug resistant is considered as a major threat to human health. Antibacterial phototherapy (PT) including photodynamic and photothermal therapy has attracted increasing attention owing to spatiotemporal precision, no drug resistance, and low systemic toxicity. However, the efficacy of photodynamic or photothermal therapy alone is limited by low oxygen concentration and high sterilization temperature, respectively. Herein, an “all in one” strategy is proposed and a porphyrin and boron dipyrromethenes (bodipy) based covalent organic framework (COF), named as Tph-BDP-COF, is synthesized to manipulate the excitation energy dissipation pathway, and thus realizing excellent synergetic antibacterial phototherapy. The “all in one” hybrid exhibits a narrow optical bandgap (1.33 eV) and a fast energy and electron transfer compare with porphyrin-base COF-366, hence improving intersystem crossing process and photothermal conversion. Thus, Tph-BDP-COF showed superior ROS generation and excellent photothermal conversion ability, consequently giving an efficient “all in one” antibacterial activities (97 %) compared with the porphyrin-based COF-366 (54 %). These findings give inspiration for the “all in one” phototherapy materials design.

Erlotinib-Modified BODIPY Photosensitizers for Targeted Photodynamic Therapy.

Photodynamic therapy (PDT) is an innovative, non-invasive and highly selective therapeutic modality for tumours and non-malignant diseases. BODIPY based molecules can function as new generation photosensitizers (PSs) in various PDT applications. Despite numerous conjugated PS systems are available, BODIPYs containing erlotinib lagged behind other photosensitizer units. In this study, smart photosensitizers containing BODIPY, erlotinib and hydrophilic units were prepared for the first time, their physicochemical properties and PDT effects were investigated. Compared with non-halogenated compound, halogenated derivatives possessed much lower fluorescence profile as well as the good ROS generation ability under red light. In vitro PDT studies were performed on both healthy (PNT1a) and prostate cancerous cells (PC3) to determine the selectivity of the compounds on cancerous cells and their effects under light. The halogenated conjugates, exposed to low dose of light illumination exhibited potent activity on cancer cell viability and the calculated IC50 values proved the high phototoxicity of the photosensitizers. It was also determined that the PSs have very low dark toxicity and that the light illumination and ROS formation are required for the initiation of the cell death mechanism. As a result, erlotinib modified BODIPYs could serve as promising agents in anticancer photodynamic therapy.

Integrated energy conversion units in nanoscale frameworks induce sustained generation and amplified lethality of singlet oxygen in oxidative therapy of tumor

AbstractReactive oxygen species (ROS) driven endoplasmic reticulum (ER) stress is highly promising for tumor therapy but restrained by the nondurable introduction and limited lifetime of oxidative species. Here, a therapeutic nanosystem with sustainable ROS generation ability was developed by accommodating luminol derivatives (L012) in hyaluronic acid‐modified metal‐organic frameworks of Fe3+ and porphyrin ligand (TCPP). After particle accumulation in the tumor, ∙OH radicals from Fe3+ sites catalyzed conversion of H2O2 can react with confined L012 transducers to generate chemiluminescence (CL). Because of the distance constraints, the CL energy was significantly extracted (96%) by adjacent TCPP and further activate oxygen to long‐lifetime singlet oxygen (1O2), whose yield can be further boosted by the catalase‐like activity of the frameworks. By regulating the substrate consumption through energy conversion, the cascade process resulted in increased ROS levels (2.4‐fold) and sustainable oxidation (24 h), which induced continuously accumulated ER stress, high autophagic levels, and amplified lethality against the tumor. This work opens a new avenue to explore reticular nanostructures with complementarily arranged and synergistically spaced conversion units in advancing ROS therapy.

ROS-responsive chlorin e6 and silk fibroin loaded ultrathin magnetic hydroxyapatite nanorods for T1-magnetic resonance imaging guided photodynamic therapy in vitro

Magnetite hydroxyapatite nanoparticles show notable multifunctional therapeutic features in nanomedicine. However, designing MHAp nanoparticles with optimum dimensions, good stability and biocompatibility for specific biomedical applications is still in its infancy. Herein, a facile approach was employed to prepare ROS-responsive chlorin e6 and silk fibroin-loaded ultrathin magnetic hydroxyapatite nanorods for T1-magnetic resonance imaging and photodynamic therapy. Specifically, the Fe3O4-HAp nanorods were synthesized by the hydrothermal method, and then Pluronic® F-127 was used to improve the aqueous dispersion, biocompatibility, and loading capacity. Moreover, silk fibroin protein was encapsulated by a tri-block copolymer with good loading efficiency. Finally, the theranostic nano-assembly MHNRs-SF-Ce6 was completed by the addition of Ce6. The prepared MHNRs demonstrated excellent biocompatibility, cellular uptake, and ROS generation ability in in vitro after 660 nm laser irradiation, leading to the apoptosis of 4T1 mouse breast cancer cells. Notably, the designed MHNRs exhibited excellent r1 relaxivity value and T1 magnetic resonance imaging in vitro due to their minimal width (2 nm) of nanorods. Therefore, the obtained MHNRs-SF-Ce6 self-assembled nanoparticles provide an effective strategy for cancer diagnosis and photodynamic therapy.

Photoswitchable semiconducting polymer dots with photosensitizer molecule and photochromic molecule loading for photodynamic cancer therapy

Photodynamic therapy (PDT) is a new and rapidly developing treatment modality for clinical cancer therapy. Semiconductor polymer dots (Pdots) doped with photosensitizers have been successfully applied to PDT, and have made progress in the field of tumor therapy. However, the problems of severe photosensitivity and limited tissue penetration depth are needed to be solved during the implementation process of PDT. Here we developed the Pdots doped with photosensitizer molecule Chlorin e6 (Ce6) and photochromic molecule 1,2-bis(2,4-dimethyl-5-phenyl-3-thiophene)-3,3,4,5-hexafluoro-1-cyclopentene (BTE) to construct a photoswitchable nanoplatform for PDT. The Ce6-BTE-doped Pdots were in the green region, and the tissue penetration depth was increased compared with most Pdots in the blue region. The reversible conversion of BTE under different light irradiation was utilized to regulate the photodynamic effect and solve the problem of photosensitivity. The prepared Ce6-BTE-doped Pdots had small size, excellent optical property, efficient ROS generation and good photoswitchable ability. The cellular uptake, cytotoxicity, and photodynamic effect of the Pdots were detected in human colon tumor cells. The experiments in vitro indicated that Ce6-BTE-doped Pdots could exert excellent photodynamic effect in ON state and reduce photosensitivity in OFF state. These results demonstrated that this nanoplatform holds the potential to be used in clinical PDT.

On-demand assembly of polymeric nanoparticles for longer-blood-circulation and disassembly in tumor for boosting sonodynamic therapy

Sonodynamic therapy (SDT) is one of the promising strategies for tumor therapy, but its application is usually hindered by fast clearance in blood-circulation, abnormal tumor microenvironment, and inefficient generation of reactive oxygen species. To solve these problems, we proposed an on-demand assembly-disassembly strategy, where the assembly is favorable for longer-blood-circulation and then the disassembly in tumor is favorable for boosting SDT. Hematoporphyrin monomethyl ether (HMME) as the model of organic sonosensitizers were conjugated with hyaluronic acid (HA). Then HA-HMME was mixed with catalase (CAT) and assembled into polymeric nanoparticles (CAT@HA-HMME NPs) with size of ∼80 nm. CAT@HA-HMME NPs exhibit good biocompatibility and a longer blood half-time (t1/2 = 4.17 h) which is obviously longer than that (∼0.82 h) of HMME molecules. After HA receptor-mediated endocytosis of cancer cells, CAT@HA-HMME NPs can be cleaved by endogenous hyaluronidase, resulting in the on-demand disassembly in tumor to release HA-HMME molecules and CAT. The CAT catalyzes the endogenous H2O2 into O2 to relieve the hypoxic microenvironment, and the released HA-HMME exhibits a higher ROS generation ability, greatly boosting SDT for the inhibition of tumor growth. Therefore, the on-demand assembly-disassembly strategy may provide some insight in the design and development of nanoagents for tumor therapy.

Facile Synthesis of NaYF4:Yb Up-Conversion Nanoparticles Modified with Photosensitizer and Targeting Antibody for In Vitro Photodynamic Therapy of Hepatocellular Carcinoma.

Rare Earth up-conversion nanoparticles NaYF4:20%Yb,2%Er@PEI (UCNPs) were generated via a one-step hydrothermal technique at relatively reduced temperatures. Photosensitizer Ce6 and anti-EpCAM, a highly expressed monoclonal antibody in cancer stem cells of hepatocellular carcinoma, were linked to UCNP surfaces via the formation of amide linkage between carboxyl from Ce6 or anti-EpCAM and abundant amino from PEI, leading to the formation of Ps-Ce6 and anti-EpCAM-UCNPs-Ce6 nanoparticles. The synthesized nanoparticles characterized by XRD, TEM, and IR, and their zeta potential, ROS generation ability, Ce6 loading rate, and up-conversion fluorescence properties were investigated. It has been revealed that all the products were uniformly dispersed nanoparticles (25–32 nm), which crystallized primarily as hexagonal structures, and their up-conversion fluorescence spectra were similar to that of NaYF4:20%Yb,2%Er. The Ce6 loading rate in the anti-EpCAM-UCNPs-Ce6 nanoparticles was about 2.9%, thereby resulting in good ROS generation ability. For anti-EpCAM-UCNPs-Ce6, the biosafety, targeting effect, and PDT effect exposed under near-infrared (NIR) laser (980 nm) were evaluated using human liver cancer cells (BEL-7404). The results showed that it has good biocompatibility and biosafety as well as high targeting and PDT treatment efficiencies, which renders it a potential experimental material for the near-infrared PDT study.

Theory-screened MOF-based single-atom catalysts for facile and effective therapy of biofilm-induced periodontitis

• The nanozymes activities of single-atom dopped MOF is presented. • Theoretical calculation screens the optimal oxidase-like single-atom dopped MOF. • The PCN-222-Pt has a strong dual enzyme-like activity and ROS generation ability. • The PCN-222-Pt shows excellent anti-biofilm performance within 1 h. • Periodontitis can be efficiently treated by injectable PCN-222-Pt nanozymes ointment. Periodontitis is a chronic inflammatory disease caused by the bacteria infection in dental plaque, which can lead to gingival recession and tooth loss, seriously endangering human oral health. Current treatments through the combination of mechanical debridement and antibiotics therapy still have the problems of gingival trauma, low treatment efficiency, long treatment cycle and bacterial resistance. Herein, we prepare an injectable ointment based on MOF-based single-atom catalysis systems with good biocompatibility and high anti-biofilm activity, which consists of PEG-400/PEG-4000 and Pt single-atom doped porphyrin metal−organic framework (PCN-222-Pt). Through theoretical screening, we find that all the metal single atoms (Pt, Au, Cu, Ru) can improve the oxidase-like activity of PCN-222, which reduce the adsorption and activation energy of O 2 . Among them, PCN-222-Pt shows strong oxidase-like and peroxidase-like activities and can produce reactive oxygen species spontaneously, which shows an excellent anti-biofilm performance (98.69% against S. aureus biofilm, 99.91% against E. coli biofilm) in vitro within 1 h. In the treatment of biofilm-induced periodontitis, the injectable PCN-222-Pt ointment showed alleviative inflammation response, reduced bone destruction and healthier gum tissue, which is superior to the clinical used Periocline. This work provides a rapid, effective, non-invasive and convenient strategy for the treatment of periodontitis without antibiotics.