Molecular characterization of Chinese patients with small bowel adenocarcinoma.

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA. METHODS: Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS. RESULTS AND CONCLUSIONS: The study found that in SBA tissues, the most commonly alternated genes were TP53, KRAS, and APC, and the most frequently affected pathways were RTK-RAS-MAPK, TP53, and WNT. Notably, the RTK-RAS-MAPK pathway was identified as a potential biomarker that could be targeted for treatment. Then, we validated the gene mutation profiling of ctDNA extracted from SBA patients exhibited the same characteristics as tissue samples for the first time. Subsequently, we applied ctDNA analysis on a terminal-stage patient who had shown no response to previous chemotherapy. After detecting alterations in the RTK-RAS-MAPK pathway in the ctDNA, the patient was treated with MEK + EGFR inhibitors and achieved a tumor shrinkage rate of 76.33%. Our study utilized the largest Chinese SBA cohort to uncover the molecular characteristics of this disease, which might facilitate clinical decision making for SBA patients.

Modular synthesis of clickable peptides via late-stage maleimidation on C(7)-H tryptophan.

Cyclic peptides have attracted tremendous attention in the pharmaceutical industry owing to their excellent cell penetrability, stability, thermostability, and drug-like properties. However, the currently available facile methodologies for creating such peptides are rather limited. Herein, we report an efficient and direct peptide cyclization via rhodium(III)-catalyzed C(7)-H maleimidation. Notably, this catalytical system has excellent regioselectivity and high tolerance of functional groups which enable late-stage cyclization of peptides. This architecture of cyclic peptides exhibits higher bioactivity than its parent linear peptides. Moreover, the Trp-substituted maleimide displays excellent reactivity toward Michael addition, indicating its potential as a click functional group for applications in chemical biology and medicinal chemistry. As a proof of principle, RGD-GFLG-DOX, which is a peptide-drug-conjugate, is constructed and it displays a strong binding affinity and high antiproliferative activity toward integrin-αvß3 overexpressed cancer cell lines. The proposed strategy for rapid preparation of stapled peptides would be a robust tool for creating peptide-drug conjugates.

Preparation and comprehensive characterization of C16MImCl/MT for adsorbing cationic dyes.

Dyeing wastewater in various industries poses a great threat to the environment. Montmorillonite (MT) is widely used in wastewater treatment because of its abundant reserves and strong exchange capacity. However, natural MT has low affinity for organic pollutants and needs to be organically modified. In order to improve the adsorption capacity of MT to cationic dyes [Congo red (CR)], using ionic liquid [1-hexadecyl-3-methylimidazolium chloride (C16MImCl)] as organic modifier, the optimal preparation process of C16MImCl/MT was determined by response surface methodology. The C16MImCl/MT was comprehensively characterized by utilizing the techniques of XRD, FTIR, TG, BET, SEM, and molecular dynamics simulation. All the research results showed that C16MImCl is successfully inserted into the layers of MT, and the basal interplanar spacing and average pore size of MT are obviously increased. The C16MImCl/MT is a mesoporous material, which shows strong adsorption capacity for CR, and its CR unit adsorption capacity (CRUAC) could reach 940.200 mg/g, which is about three times that of magnetic graphene oxide and bentonite/expanded graphite.

Corrigendum: Longitudinal Circulating Tumor DNA Profiling in Metastatic Colorectal Cancer During Anti-EGFR Therapy.

[This corrects the article DOI: 10.3389/fonc.2022.830816.].

Clinical Benefit With PARP Inhibitor for Pathogenic Germline FANCA-Mutated Relapsed Epithelial Ovarian Cancer: A Case Report.

Background: PARP inhibitors have been approved as targeted therapy for BRCA-deficient metastatic ovarian cancer (OC). Fanconi anemia complementation group A (FANCA), one of the homologous recombination repair pathway genes, is a susceptibility gene to breast cancer and OC. Therefore, it is interesting to investigate whether germline FANCA-mutated relapsed epithelial OC could achieve clinical benefit from the treatment of PARP inhibitor. Case Presentation: A 49-year-old female patient without a family history of cancer was diagnosed with epithelial OC. This patient underwent surgical resection plus platinum-based treatment twice in 2016 and 2018, successively. After the second relapse in July 2019, the patient underwent another radical resection. The next-generation sequencing analysis results revealed a germline FANCA mutation in the tumor tissue. Subsequently, the third-line treatment of liposomal doxorubicin hydrochloride plus lobaplatin was administrated for five cycles with the patient's consent. Then, oral niraparib (200 mg daily) was given for maintenance treatment. During the follow-up, no evidence of tumor recurrence was observed. Currently, the survival with no evidence of disease has already exceeded 21 months, and the treatment is still going on. Conclusions: This case highlighted that OC patients harboring pathogenic gene alterations in the homologous recombination pathway might achieve clinical benefit from PARP inhibitors, which should be confirmed in further studies.

Longitudinal Circulating Tumor DNA Profiling in Metastatic Colorectal Cancer During Anti-EGFR Therapy.

Background: Metastatic colorectal cancer (mCRC) is a heterogenous disease with limited precision medicine and targeted therapy options. Monoclonal antibodies against epidermal growth factor receptor (EGFR) have been a crucial treatment option for mCRC. However, proper biomarkers for predicting therapeutic response remain unknown. As a non-invasive test, circulating tumor DNA (ctDNA) is appropriately positioned to reveal tumor heterogeneity and evolution, as it can be used in real-time genomic profiling. To evaluate the significance of ctDNA in monitoring the dynamic therapeutic response and prognosis of mCRC, we detected the baseline and dynamic changes of ctDNA in mCRC patients receiving anti-EGFR therapies. Methods: A single-center study was conducted retrospectively. Plasma samples from mCRC patients who received anti-EGFR therapies were collected at baseline and continuous treatment points. The ctDNA was extracted and sequenced with a target panel of tumor-related genes via next-generation sequencing (NGS). Clinical information was also collected and analyzed. Results: We conducted dynamic sampling of 22 mCRC patients, analyzed 130 plasma samples, obtained a baseline genomic mutation profile of the patients. In total, 54 variations were detected in 22 plasma samples, with a positive rate of 77.3% (17/22). TP53 was the most mutated gene (59.1%, 13/22), followed by APC (18.2%, 4/22). There was a high concordance rate of genomic characteristics between the tumor tissue test by polymerase chain reaction and ctDNA test by NGS. The mutation discrepancy increased with an extended course of treatment. During remission TP53 and APC were the most frequently decreased clonal mutations and KRAS, NRAS, ERBB2 and PIK3CA were the most decreased subclonal mutations. Both mutation types were increased during progression. The ctDNA decreased earlier than did the responses of computed tomography and traditional tumor markers (carbohydrate antigen 19-9 and carcinoembryonic antigen [CEA]). Lactate dehydrogenase level (P = 0.041), CEA level (P = 0.038), and primary lesion site (P = 0.038) were independent risk factors that influenced overall survival. Moreover, patients with RAS mutations tended to have a worse prognosis (P = 0.072). Conclusions: This study demonstrates that ctDNA is a promising biomarker for monitoring the dynamic response to treatment and determining the prognosis of mCRC.

Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades.

The common gamma receptor-dependent cytokines and their JAK-STAT pathways play important roles in T cell immunity and have been demonstrated to be related with response to immune checkpoint blockades (ICBs). PTPRD and PTPRT are phosphatases involved in JAK-STAT pathway. However, their clinical significance for non-small cell lung cancer (NSCLC) treated with ICBs is still unclear. Genomic and survival data of NSCLC patients administrated with anti-PD-1/PD-L1 or anti-CTLA-4 antibodies (Rizvi2015; Hellmann2018; Rizvi2018 Samstein2019) were retrieved from publicly accessible data. Genomic, survival and mRNA data of 1007 patients with NSCLC were obtained from The Cancer Genome Atlas (TCGA). PTPRD/PTPRT mutation was significantly associated with better progression-free survival (PFS) in three independent Rizvi2015, Hellmann2018 and Rizvi2018 cohorts. The median PFS for PTPRD/PTPRT mutant-type vs. wild-type NSCLC patients were not reached vs. 6.3 months (Rizvi2015, HR = 0.16; 95% CI, 0.02-1.17; P=0.03), 24.0 vs. 5.4 months (Hellmann2018, HR, 0.49; 95% CI, 0.26-0.94; P=0.03), 5.6 vs. 3.0 months (Rizvi2018, HR = 0.64; 95% CI, 0.44-0.92; P=0.01) and 6.8 vs. 3.5 months (Pooled cohort, HR, 0.54; 95% CI, 0.39-0.73; P<0.0001) respectively. PTPRD/PTPRT mutation was an independent predictive factor for PFS in pooled cohort (P = 0.01). Additionally, PTPRD/PTPRT mutation associated with better overall survival (OS) in Samstein2019 cohort (19 vs. 10 months, P=0.03). While similar clinical benefits were not observed in patients without ICBs treatment (TCGA cohort, P=0.78). In the further exploratory analysis, PTPRD/PTPRT mutation was significantly associated with increased tumor mutation burden and higher mRNA expression of JAK1 and STAT1. Gene Set Enrichment Analysis revealed prominent enrichment of signatures related to antigen processing and presentation in patients with PTPRD/PTPRT mutation. This work suggested that PTPRD/PTPRT mutation might be a potential positive predictor for ICBs in NSCLC. These results need to be further confirmed in future.

Recent Advances in Late-Stage Construction of Stapled Peptides via C-H Activation.

Stapled peptides have been widely applied in many fields, including pharmaceutical chemistry, diagnostic reagents, and materials science. However, most traditional stapled peptide preparation methods rely on prefunctionalizations, which limit the diversity of stapled peptides. Recently, the emergence of late-stage transition metal-catalyzed C-H activation in amino acids and peptides has attracted wide interest due to its robustness and applicability for peptide stapling. In this review, we summarize the methods for late-stage construction of stapled peptides via transition metal-catalyzed C-H activation.

The role of TGF-ß pathway alterations in immune regulation as a potential pan-cancer biomarker in immunotherapy.

BACKGROUND: Depending on the context, the transforming growth factor beta (TGF-ß) signaling pathway is involved in opposing cell processes of tumor suppression and tumor promotion. However, the effects of TGF-ß pathway on immunotherapy efficacy have not yet been systematically investigated. METHODS: In this study, we have extracted the available data of whole-exome sequencing, messenger RNA (mRNA) expression, baseline characterization, and prognosis information of 10,912 pan-cancer patients from The Cancer Genome Atlas to explore the role of TGF-ß pathway in immune regulation. Formalin-fixed, paraffin-embedded tissue samples from 6,717 Chinese cancer patients assayed by next-generation sequencing (NGS) were used as a validation cohort (3DMed cohort). Data sets from the public MSK (Memorial Sloan Kettering Cancer Center) cohort (N=1,610) were used to explore the association of TGF-ß pathway with immunotherapy effects. RESULTS: The results showed that TGF-ß pathway alteration was significantly correlated with high microsatellite instability (MSI), high tumor mutational burden, and high neoantigen burden (TNB) (P<0.001 for each). Consistently, the pathway mutations were associated with distinct patterns of immune-related gene expression and tumor-infiltrating immune cells. Patients with TGF-ß pathway mutations exhibited significantly worse prognosis than did the wild-type patients regardless of the interventions [overall survival (OS): hazard ratio (HR) 1.20; 95% confidence interval (CI): 1.08-1.33; P=0.001]. However, when treated with immune checkpoint inhibitors (ICIs), superior survival benefit was observed in patients from the mutation group versus the wild-type group (OS: HR 0.73; 95% CI: 0.61-0.88; P=0.001). CONCLUSIONS: Collectively, our study suggested that mutations in TGF-ß pathway may be associated with positive immune regulation and better efficacy of immunotherapy.

Case Report: Durable Clinical Response to Third-Line Pyrotinib After Resistance to Trastuzumab in a Gastric Cancer Patient.

BACKGROUND: Trastuzumab plus chemotherapy remains the standard first-line treatment strategy for HER2-positive gastric cancer (GC). Trastuzumab resistance, on the other hand, remains a significant issue. There are a few effective anti-HER2 agents for patients who develop resistance to trastuzumab. CASE PRESENTATION: A 49-year-old female was diagnosed with stage IV GC with liver and lung metastasis in July 2017. She underwent gastrostomy, and the immunohistochemistry (IHC) result of postoperative tissue demonstrated HER2 (3+). She received first-line treatment of trastuzumab (440 mg), oxaliplatin (200 mg), and S-1 (40 mg). After treatment for 6 months, the patient achieved complete response (CR) with PFS up to 21 months. After progression, she subsequently received trastuzumab (440 mg) plus oxaliplatin (200 mg) as second-line treatment. However, the patient developed resistance to trastuzumab after 12 months of treatment. She started to receive third-line treatment of irinotecan (200 mg d1) and capecitabine (60 mg bid) plus pyrotinib (400 mg/day). After 2 months of treatment, the tumor is evaluated as partial response with PFS of 12 months. CONCLUSIONS: We presented a patient with HER2-positive GC who benefited from the pyrotinib-based treatment after two lines of trastuzumab-based therapies failed. Further research is required to validate such conclusions.

Response to Afatinib in a Patient with NSCLC Harboring Novel EGFR Exon 20 Insertion Mutations.

PURPOSE: Most epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are resistant to tyrosine kinase inhibitors (TKIs). While some non-small cell lung cancer (NSCLC) patients harboring special subtypes of EGFR ex20ins still achieved clinical response after TKIs treatment, identifying special subtypes of EGFR ex20ins is helpful to find out NSCLC patients who can respond to TKIs. CASE PRESENTATION: A 71-year-old non-smoker Chinese female was diagnosed with advanced lung adenocarcinoma harboring EGFR ex20ins (N771delinsKG). The patient received first-line afatinib (40 mg/day) therapy and a significant and substantial reduction in tumor size was observed subsequently. According to RESIST 1.1, a radiological partial response was achieved. The final progression-free survival was 10 months. CONCLUSION: This is the first published case report of EGFR N771delinsKG lung adenocarcinoma, which highlighted the heterogeneity of clinical response to TKIs for EGFR ex20ins-mutant NSCLC. Such results need to be further investigated in prospective studies.

Hyperprogression to camrelizumab in a patient with esophageal squamous cell carcinoma harboring EGFR kinase domain duplication.

BACKGROUND: Previous studies have reported that the amplification of some genes, such as Murine Double Minute 2 or 4 and Epidermal Growth Factor Receptor (EGFR), may be related to hyperprogressive disease (HPD). Exploring somatic gene alterations might be an effective method to predict HPD. Herein we characterize the somatic alterations in a patient with esophageal squamous cell carcinoma (ESCC) who developed HPD to investigate the potential origins of HPD. CASE PRESENTATION: A man in his mid-40s was diagnosed with ESCC. After the failure of first-line treatment with cisplatin and docetaxel, the patient participated in a phase III randomized, open, multicenter clinical trial (CTR20170307) and subsequently received camrelizumab. After 4 weeks of immunotherapy, the tumor size increased by 79% compared with baseline imaging; the progressive pace was 2.5-fold higher than preimmunotherapy, and a new liver metastasis appeared. A rare EGFR exon 2-28 duplication was discovered in both preimmunotherapy and postimmunotherapy tumor tissues. CONCLUSION: This is the first report on a patient with ESCC harboring rare EGFR kinase domain duplication in exons 2-28 and developing HPD in the process of camrelizumab treatment. This case suggested that EGFR kinase domain duplication might be associated with HPD. Administration of immune checkpoint inhibitor monotherapy in this subgroup of patients harboring EGFR kinase domain duplication should be performed with caution. These results need to be further confirmed in a larger cohort of patients.

Flotation dynamics of metal and non-metal components in waste printed circuit boards.

Flotation is an effective and clean separation technology to realize the recovery of metal in waste printed circuit boards (WPCBs). The flotation kinetic of metal and non-metal components was concerned in this study. In addition, the loading of bubbles, the collision and shedding of particles and bubbles were used to assist in proving the particle dynamics results. By analyzing the force on the particles, the load of bubbles on particles was analyzed, and the appropriate volume ratio of bubbles to particles was 1.5-8.0, depending on the particle density. Moreover, Clift model and Schiller-Naumann model has high fitting accuracy for the final bubble velocity. In addition, metal particles have greater settling velocity, which results in shorter collision time with bubbles. In the process of bubble-particle rising, the shedding probability gradually decreases, and the shedding probability of metal particles is much higher than that of non-metal particles. The results of flotation kinetics show that the removal of impurity particles represented by silicon mainly occurs in the initial stage of flotation process. The loss of copper increases with flotation time and collector dosage. This study reveals the flotation kinetics of particles from the perspectives of bubble loading, bubble-particle collision and shedding.

Construction of a chiral artificial enzyme used for enantioselective catalysis in live cells.

Nanozymes as a newcomer in the artificial enzyme family have shown several advantages over natural enzymes such as their high stability in harsh environments, facile production on large scale, long storage time, low costs, and higher resistance to biodegradation. However, compared with natural enzymes, it is still a great challenge to design a nanozyme with high selectivity, especially high enantioselectivity. It is highly desirable and demanding to develop chiral nanozymes with high and on-demand enantioselectivity for practical applications. Herein, we present an unprecedented approach to construct chiral artificial peroxidase with ultrahigh enantioselectivity. Inspired by the structure of the natural enzyme horseradish peroxidase (HRP), we have constructed a series of stereoselective nanozymes (Fe3O4@Poly(AA)) by using the ferromagnetic nanoparticle (Fe3O4 NP) yolk as the catalytic core and amino acid-appended chiral polymer shell as the chiral selector. Among them, Fe3O4@Poly(d-Trp) exhibits the highest enantioselectivity. More intriguingly, their enantioselectivity will be readily reversed by replacing d-Trp with l-Trp. The selectivity factor is up to 5.38, even higher than that of HRP. Kinetic parameters, dialysis experiments, and molecular simulations together with activation energy reveal that the selectivity originates from the d-/l-Trp appended polymer shell, which can result in better affinity and catalytic activity to d-/l-tyrosinol. The artificial peroxidases have been used for asymmetric catalysis to prepare enantiopure d- or l-enantiomers. Besides, by using fluorescent labelled FITC-tyrosinolL and RhB-tyrosinolD, the artificial peroxidases can catalyze green or red fluorescent chiral tyrosinol to selectively label live yeast cells among yeast, S. aureus, E. coli and B. subtilis bacterial cells. This work opens a new avenue for better design of stereoselective artificial enzymes.

Response to Afatinib in a Patient with Non-Small Cell Lung Cancer Harboring HER2 R896G Mutation: A Case Report.

PURPOSE: HER2 mutations are identified in approximately 2% of non-small-cell lung cancer (NSCLC) cases; however, until now, there are no approved standard targeted therapy for NSCLC patients harboring HER2 mutations. CASE PRESENTATION: We present a 63-year-old male with a long smoking history, who was diagnosed with stage IV squamous cell lung cancer. After the failures of two lines of treatment with carboplatin plus gemcitabine and nidaplatin plus docetaxel, in turn, the patient received a next-generation sequencing of circulating tumor DNA to seek for potential treatment opportunities. A HER2 R896G mutation was identified with an allelic fraction of 50.77%. The patient received afatinib 40 mg a day and reached a partial response after two months of treatment. The progression-free survival was more than 14 months and the treatment of afatinib was ongoing. During the treatment, treatment-related paronychia and stomatitis occurred and relieved without any management. CONCLUSION: This is the first case report describing a NSCLC patient harboring a rare HER2 R896G mutation who responds to afatinib. This case suggests that afatinib might be efficacious in NSCLC patients harboring HER2 R896G mutations, and these results need to be further studied in prospective clinical trials.

A Sequential Target-Responsive Nanocarrier with Enhanced Tumor Penetration and Neighboring Effect In Vivo.

Nanodrug-based cancer therapy is impeded by poor penetration into deep tumor tissues mainly due to the overexpression of hyaluronic acid (HA) in the tumor extracellular matrix (ECM). Although modification of nanoparticles (NPs) with hyaluronidase (HAase) is a potent strategy, it remains challenging to get a uniform distribution of drug at the tumor site because of the internalization of NPs by the cells in the tumor and HA regeneration. Herein, an intelligent nanocarrier, which can release HAase in response to the acidic tumor microenvironment (pH 6.5) and perform a strong neighboring effect with size reduction to overcome the above two problems and accomplish drug deep tumor penetration in vivo, is reported. In this design, HAase is encapsulated on the surfaces of doxorubicin (DOX) preloaded ZnO-DOX NPs using a charge convertible polymer PEG-PAH-DMMA (ZDHD). The polymer can release HAase to degrade HA in the tumor ECM (pH 6.5). ZnO-DOX NPs can release DOX in lysosomes (pH 4.5) to induce cell apoptosis, and exert a neighboring effect with size reduction to infect neighboring cells. The hierarchical targeted release of HAase and drugs is demonstrated to enhance tumor penetration and decrease side effects in vivo. This work shows promise for further application of ZDHD NPs in cancer therapy.

Two-Dimensional Metal-Organic Framework/Enzyme Hybrid Nanocatalyst as a Benign and Self-Activated Cascade Reagent for in Vivo Wound Healing.

Metal-organic frameworks (MOFs)-based peroxidase mimics have been seldom applied in the biomedical field, especially in vivo. One of the main reasons is their optimum reactions occur in strong acidic environments with a pH of 3-4, severely limiting their applications in living systems where neutral pH is usually required. Other types of peroxidase mimics also suffer such a fatal defect. Additionally, the direct introduction of the relatively high concentrated and toxic reaction reagent H2O2 would induce undesired damage to normal tissues. Herein, a MOF-based hybrid nanocatalyst as a benign and self-activated cascade reagent has been constructed. Owing to better catalytic performance compared with three-dimensional bulk MOF, an ultrathin two-dimensional (2D) MOF (2D Cu-TCPP(Fe)) nanosheet is chosen as a model of peroxidase mimic to physically adsorb glucose oxidase (GOx) for fabricating such a hybrid nanocatalyst. Nontoxic glucose can be continuously converted into abundant gluconic acid and H2O2 by GOx, avoiding the direct use of relatively high concentrated and toxic H2O2 and minimizing the harmful side effects. The generated gluconic acid can decrease the pH value from 7 to 3-4, dramatically activating the peroxidase-like activity of 2D Cu-TCPP(Fe) nanosheets. Meanwhile, the produced H2O2 is used for subsequent catalysis of activated 2D Cu-TCPP(Fe) nanosheets, leading to efficient generation of an extremely toxic hydroxyl radial and antibacterial capacity. In vitro and in vivo results illustrate the designed benign and self-activated cascade reagent possesses a robust antibacterial effect with negligible biotoxicity.

Manipulating cell fate: dynamic control of cell behaviors on functional platforms.

The cell microenvironment choreographs the behaviors of cells through multiple well-controlled signals. For basic biological study and cell-based therapies, it is essential to decipher the complicated cell-matrix interactions, and to develop ways to mimic the dynamic microenvironment so that desired biological functions of cells can be guided. For this, biomaterials with the ability to spatiotemporally impart biochemical and biophysical cues to manipulate cell fate have been developed recently. The dynamic property and programmable features of stimuli-responsive biointerfaces endow them with the outstanding ability to develop advanced biological systems. In this review, we illustrate the recent progress of stimuli-responsive biosystems with a particular emphasis on their explorations for cell-based fundamental studies, disease diagnosis and regenerative therapy. Some basic principles and strategies for the design of dynamic platforms are also discussed in this review. Finally, we conclude with an outlook on current challenges and future of dynamic platforms for cell study and biomedical applications. Overall, we anticipate that this review will boost the development of dynamic and multifunctional biosystems by inspiring interest from various disciplines, including chemistry, materials science, cell biology, nanotechnology, biomedical engineering, as well as clinical research.

A H2O2-free depot for treating bacterial infection: localized cascade reactions to eradicate biofilms in vivo.

Peroxidase-like nanoparticles are promising materials to treat bacterial infection through catalyzing H2O2 into more toxic highly reactive oxygen species (hROS; such as hydroxyl radicals). However, all the reported related strategies, to the best of our knowledge, depend on the usage of extra H2O2, limiting the applications of peroxidase-like nanoparticles. Thus, it is necessary to develop peroxidase-based materials without extra H2O2. In this report, H2O2-free depots are prepared by integrating CaO2 and hemin-loading graphene (H-G) into alginate (CaO2/H-G@alginate). They can convert H2O into hROS through localized cascade reactions at the site of bacterial infection and damage the main components of biofilms (bacteria, polysaccharides, proteins, and nucleic acids). Besides, the confined environment of depots can reduce the potential risk from H2O2 and improve the cascade catalytic activity. This is the first example of exploring peroxidase-like nanozymes without extra H2O2 to treat bacterial infection.