Survival prognostic in different age groups of patients undergoing local versus radical excision for rectal cancer: a study based on the SEER database.

Age significantly affects the prognosis of patients with rectal cancer after radical excision (RE), and local excision (LE) is an alternative surgical procedure to RE. To compare the survival prognosis in different age groups of LE versus RE for rectal cancer. Patients diagnosed with rectal adenocarcinoma treated by LE or RE from 2010 to 2017 were obtained from the SEER database. The primary outcomes are 5-year OS and CSS. A total of 11,170 patients were eventually included, and there were 490 patients in LE and RE groups, respectively, after 1:1 propensity score matching. The 5-year OS and CSS after LE were significantly better in < 50 years and 50-66 years groups than in > 66 years group (5-year OS: 95.70% vs 88.40% vs 67.00%, P < 0.001; 5-year CSS: 95.70% vs 96.30% vs 82.60%, P < 0.001). No statistical significance was found for the differences in 5-year OS and CSS between LE and RE in < 50, 50-66, and > 66 years group (P > 0.05). Multivariate analysis showed age > 66 years, poorly differentiated or undifferentiated (Grade III/IV), and tumor size 3 to 5 cm was independent risk factors for 5-year OS after LE; age > 66 years, perineural invasion, and tumor size 3 to 5 cm were the 5-year CSS independent risk factors for after LE. We found that the survival prognosis of younger rectal cancer patients treated with LE was significantly better than older (> 66 years) patients, and the survival prognosis of rectal cancer patients in the three age groups was similar between LE and RE.

CPE correlates with poor prognosis in gastric cancer by promoting tumourigenesis.

Aims: To investigate the potential functions and mechanisms of tumourigenesis in carboxypeptidase E (CPE) and its prognostic value in gastric cancer, and to develop a predictive model for prognosis based on CPE. Results: Transcriptome level variation and the prognostic value of CPE in different types of cancers were investigated using bioinformatics analyses. The association between CPE and clinicopathological characteristics was specifically explored in gastric cancer. Elevated CPE expression was associated with poor survival and recurrence prognosis and was found in cases with a later clinical stage of gastric cancer. The CPE was considered an independent prognostic factor, as assessed using Cox regression analysis. The prognostic value of CPE was further verified through immunohistochemistry and haematoxylin staining. Enrichment analysis provided a preliminary confirmation of the potential functions and mechanisms of CPE. Immune cell infiltration analysis revealed a significant correlation between CPE and macrophage infiltration. Eventually, a prognosis prediction nomogram model based on CPE was developed. Conclusion: CPE was identified as an independent biomarker associated with poor prognosis in gastric cancer. This suggests that CPE overexpression promoted epithelial-mesenchymal transition via the activation of the Erk/Wnt pathways, leading to proliferation, invasion, and metastasis. Targeted therapeutic strategies for gastric cancer may benefit from these findings.

DNA-Based Fluorescent Nanoprobe for Cancer Cell Membrane Imaging.

As an important barrier between the cytoplasm and the microenvironment of the cell, the cell membrane is essential for the maintenance of normal cellular physiological activities. An abnormal cell membrane is a crucial symbol of body dysfunction and the occurrence of variant diseases; therefore, the visualization and monitoring of biomolecules associated with cell membranes and disease markers are of utmost importance in revealing the biological functions of cell membranes. Due to their biocompatibility, programmability, and modifiability, DNA nanomaterials have become increasingly popular in cell fluorescence imaging in recent years. In addition, DNA nanomaterials can be combined with the cell membrane in a specific manner to enable the real-time imaging of signal molecules on the cell membrane, allowing for the real-time monitoring of disease occurrence and progression. This article examines the recent application of DNA nanomaterials for fluorescence imaging on cell membranes. First, we present the conditions for imaging DNA nanomaterials in the cell membrane microenvironment, such as the ATP, pH, etc. Second, we summarize the imaging applications of cell membrane receptors and other molecules. Finally, some difficulties and challenges associated with DNA nanomaterials in the imaging of cell membranes are presented.

Prognostic impact of tumor budding in rectal cancer after neoadjuvant therapy: a systematic review and meta-analysis.

BACKGROUND: Tumor budding (TB) is a negative prognostic factor in colorectal cancer; however, its prognostic impact following neoadjuvant therapy for patients with rectal cancer remains unclear. This study aims to assess the prognostic impact of TB and the correlation between TB and other pathological features in patients with rectal cancer after neoadjuvant therapy. METHODS: A comprehensive search of PubMed, Embase, Cochrane, Scopus, CNKI, Wanfang, and ClinicalKey databases was conducted for studies on the prognosis of TB in rectal cancer after neoadjuvant therapy from the inception of the databases to January 2023, and the final literature included was determined using predefined criteria. Quality assessment of the studies included, extraction of general and prognostic information from them, and meta-analyses were carried out progressively. RESULTS: A total of 11 studies were included, and the results of the meta-analysis showed that high-grade tumor budding (TB-1) increased the risk of poor 5-year disease-free survival (HR = 1.75, 95% CI 1.38-2.22, P < 0.00001), 5-year overall survival (HR = 1.77, 95% CI 1.21-2.59, P = 0.003), local recurrence (OR = 4.15, 95% CI 1.47-11.75, P = 0.007), and distant metastasis (OR = 5.36, 95% CI 2.51-11.44, P < 0.0001) in patients with rectal cancer after neoadjuvant therapy. TB-1 was significantly associated with poor differentiation and lymphatic, perineural, and venous invasion. CONCLUSION: Tumor budding is significantly correlated with unfavorable prognosis and poor pathological characteristics following neoadjuvant therapy for rectal cancer. We anticipate more high-quality, prospective studies in the future to confirm our findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022377564.

Ratiometric Electrochemiluminescence of Zirconium Metal-Organic Framework as a Single Luminophore for Sensitive Detection of HPV-16 DNA.

This study developed a new zirconium metal-organic framework (MOF) luminophore named Zr-DPA@TCPP with dual-emission electrochemiluminescence (ECL) characteristics at a resolved potential. First, Zr-DPA@TCPP with a core-shell structure was effectively synthesized through the self-assembly of 9,10-di(p-carboxyphenyl)anthracene (DPA) and 5,10,15,20-tetra(4-carboxyphenyl)porphyrin (TCPP) as the respective organic ligands and the Zr cluster as the metal node. The reasonable integration of the two organic ligands DPA and TCPP with ECL properties into a single monomer, Zr-DPA@TCPP, successfully exhibited synchronous anodic and cathodic ECL signals. Besides, due to the impressively unique property of ferrocene (Fc), which can quench the anodic ECL but cannot affect the cathodic ECL signal, the ratiometric ECL biosensor was cleverly designed by using the cathode signal as an internal reference. Thus, combined with DNA recycle amplification reactions, the ECL biosensor realized sensitive ratiometric detection of HPV-16 DNA with the linear range of 1 fM-100 pM and the limit of detection (LOD) of 596 aM. The distinctive dual-emission properties of Zr-DPA@TCPP provided a new idea for the development of ECL luminophores and opened up an innovative avenue of fabricating the ratiometric ECL platform.

Endogenous Adenosine Triphosphate-Assisted Three-Dimensional DNA Walker Assembled on Soft Nanoparticles for Intracellular MicroRNA Imaging.

DNA walkers, a sophisticated type of nanomachines, exhibit intelligent application in biosensing with high programmability and flexibility but usually need additional auxiliary driving force, particularly when walking on hard surfaces. Herein, we construct a three-dimensional (3D) DNA walker on the soft surface of DNA nanospheres (DSs) by using a single-stranded DNA (ssDNA), which is powered by endogenous adenosine triphosphate (ATP) of live cells, so as to sensitively image microRNA (miRNA) in the tumor microenvironment. When the DS walker enters into live cells, miR-21, a general overexpressed biomarker in cancer cells, binds with the blocking strand (B), releasing the walking strand (W) and triggering an ATP-propelled walking reaction. The walking of the DS walker then generates an increasing Cy3 fluorescence signal that indicates the content of miR-21 with about 2.73-fold increase in sensitivity and about 157-fold decrease in the detection limit. Notably, the assembly of the DS walker on soft nanoparticles needs just an easy hybridization process, which facilitates the operation. Meanwhile, this endogenous ATP-powered 3D DNA walker walking on the soft surface performs real-time in situ imaging of miR-21 in live cells, which not only avoids the complex cell treatment and signal error induced by additional auxiliary factors, but also shows high promise of designing programmable DNA nanomachines.

Development of a prognostic model based on ferroptosis-related genes for colorectal cancer patients and exploration of the biological functions of NOS2 in vivo and in vitro.

Background: Ferroptosis is involved in many malignant tumors and has been implicated in important mechanisms of colorectal cancer (CRC) suppression. However, the prognostic and predictive values of the ferroptosis activation pattern in CRC patients have not been noted. Here, we aimed to construct and validate a prediction model based on ferroptosis-related genes (FRGs) for CRC patients and investigated the expression pattern and biological function of the most significantly altered gene. Methods: A total of 112 FRGs were obtained from the FerrDb website, and the clinical characteristics of 545 CRC patients and their global gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. Survival-related FRGs were identified by Cox proportional hazards regression analysis. Finally, the expression pattern and biological function of NOS2, the most implicated gene was explored in vitro and in vivo. Results: The prediction model was established based on 8 FRGs. Patients in the high- or low-risk group were stratified based on the median risk value calculated by our model, and patients in the high-risk group experienced poor overall survival (p<0.01). Further validation demonstrated that the FRG model acted as an independent prognostic indicator for CRC patients (HR=1.428, 95% CI, 1.341-1.627; p<0.001). The area under the receiver operating characteristic (ROC) curve (AUC) for 5-year survival was 0.741. NOS2 was one of the most significantly affected FRGs and was highly expressed in malignant tissue, but it inhibited tumor growth and induced tumor cell death in vitro and in vivo, possibly by repressing the NF-κB pathway. Conclusion: Our study revealed that FRGs have potential prognostic value in CRC patients and that NOS2 suppresses tumor progression, providing a novel therapeutic target for CRC treatment based on ferroptosis.

Delivery of Engineered Primary Tumor-Derived Exosomes Effectively Suppressed the Colorectal Cancer Chemoresistance and Liver Metastasis.

Liver metastasis is one of the major causes of colorectal cancer (CRC)-related morbidity and mortality. Delivering small interfering RNAs (siRNAs) or noncoding RNAs has been reported as a promising method to target liver metastasis and chemoresistance in CRC. Here, we report a noncoding RNA delivery system using exosomes derived from primary patient cells. Coiled-coil domain-containing protein 80 (CCDC80) was strongly associated with CRC liver metastasis and chemoresistance, a finding validated by bioinformatic analysis and clinical specimens. Silencing CCDC80 significantly increased sensitivity to chemotherapy agents in OXA-resistant cell lines and a mouse model. The primary cell-derived exosome delivery system was designed to simultaneously deliver siRNAs targeting CCDC80 and increase chemotherapy sensitivity in the distant CRC liver metastasis mouse models and patient-derived xenograft mouse models. We further validated the antitumor effect in an ex vivo model of chemoresistant CRC organoids and a patient-derived organoid xenograft model. Tumor-bearing mice treated with the siRNA-delivering exosomes and hepatectomy showed ideal overall survival. Our results provide a therapeutic target and represent a possible therapeutic alternative for patients with CRC and distant metastasis and in cases of chemoresistance.

Logic Control of Directional Long-Range Resonance Energy Transfer On 2D DNA Nanosheet.

By arranging fluorophores in a directional way on a 2D DNA nanosheet that transfers energy from the initial donor to the acceptor through homogeneous Förster resonance energy transfer (homo-FRET), it is found that the photonic wires (PWs) based on cascade long-range resonance energy transfer (LrRET) up to 15.6 nm can be effectively achieved through the rational selection of the fluorophores and the adjustment of their position with different distance. Then, logic control of directional energy transfer is achieved with the blocking of the energy transfer pathway, making two tumor-associated microRNA (miRNA) inputs produce an obvious output with the association of tumor diagnosis only when they present simultaneously. This research provides a new thought for development of PWs on 2D DNA nanosheets and a smart application of LrRET-based DNA AND logic control of intracellular miRNA imaging and tumor cells recognition.

MicroRNA Imaging Encounters Rolling Circle Amplification: Intracellular Na+-Fueled Linear Programmable DNAzyme Nanostructure.

DNAzyme motors are widely used for the sensitive detection of intracellular miRNAs due to their excellent signal response. Generally, the addition of exogenous mental ions to DNAzyme motors is crucial for the efficient operation of the system. Moreover, the position of the DNAzyme relative to the substrate has a significant impact on the cleavage rate during the reaction. Herein, we proposed a highly loaded Na+-fueled linear programmable DNAzyme nanostructure (LPDN) composed of long, single-strand DNA produced by rolling circle amplification reactions that served as binding partners for Na+-specific DNAyme and substrate. In the meantime, the long, programmable scaffolds can precisely control the position of the DNAzyme and substrate for the optimal effect. During the assay, miR-21 and endogenous Na+ can specifically trigger multiple adjacent substrate-cleaving reactions, resulting in a significant recovery of the Cy3 fluorescence signal in living cells. This method could enable in situ real-time imaging and biocompatibility-enhancing evaluation of intracellular miR-21-level changes. Furthermore, LPDN's ability to distinguish normal cells from cancer cells makes it a promising candidate for early cancer diagnosis and imaging analysis of cancer.

High-Efficiency Aluminum-Metal Organic Framework/HEPES Electrochemiluminescence System for Ultrasensitive Detection of HBV DNA.

In this work, a novel aluminum metal-organic framework (Al-MOF)/N-2-hydroxyethylpiperazine-N'-ethane-sulfonic acid (HEPES) system with an excellent electrochemiluminescence (ECL) property was developed. First, Al-MOF was successfully synthesized through a one-pot solvothermal method by using 9,10-di(p-carboxyphenyl)anthracene (DPA) as the organic luminescence ligand and Al3+ as the metal node. Compared with DPA, Al-MOF showed high ECL intensity and excellent stability without an additional coreactant in the HEPES buffer. The corresponding ECL mechanism was studied in detail, verifying HEPES was not only the buffer in the system but also the coreactant of Al-MOF. In particular, the system of Al-MOF/HEPES showed a high ECL efficiency of 30.0%, taking the Ru(bpy)32+ system as the standard. In addition, the ECL signal of Al-MOF was effectively quenched by dopamine (DA). The biosensor for HBV DNA detection was constructed through the ECL signal on-off-on mode of DNA specific recognition integrated with the DNA walker signal amplification strategy. The ultrasensitive detection for HBV DNA was achieved with a linear range of 100 aM to 10 pM and a limit of detection (LOD) of 62.1 aM. This work proposed a high-efficiency Al-MOF/HEPES system, providing a new viewpoint for a coreactant-free system in the field of ECL.

Multi-Catcher Polymers Regulate the Nucleolin Cluster on the Cell Surface for Cancer Therapy.

Cell signal transduction mediated by cell surface ligand-receptor is crucial for regulating cell behavior. The oligomerization or hetero-aggregation of the membrane receptor driven by the ligand realizes the rearrangement of apoptotic signals, providing a new ideal tool for tumor therapy. However, the construction of a stable model of cytomembrane receptor aggregation and the development of a universal anti-tumor therapy model on the cellular surface remain challenging. This work describes the construction of a "multi-catcher" flexible structure GC-chol-apt-cDNA with a suitable integration of the oligonucleotide aptamer (apt) and cholesterol (chol) on a polymer skeleton glycol chitosan (GC), for the regulation of the nucleolin cluster through strong polyvalent binding and hydrophobic membrane anchoring on the cell surface. This oligonucleotide aptamer shows nearly 100-fold higher affinity than that of the monovalent aptamer and achieves stable anchoring to the plasma membrane for up to 6 h. Moreover, it exerts a high tumor inhibition both in vitro and in vivo by activating endogenous mitochondrial apoptosis pathway through the cluster of nucleolins on the cell membrane. This multi-catcher nano-platform combines the spatial location regulation of cytomembrane receptors with the intracellular apoptotic signaling cascade and represents a promising strategy for antitumor therapy.

Precision medicine-guided co-delivery of ASPN siRNA and oxaliplatin by nanoparticles to overcome chemoresistance of colorectal cancer.

The development of chemoresistance is a major hurdle for the treatment of colorectal cancer (CRC), which contributes remarkably to the poor clinical prognosis. Nanodrug delivery systems show great potential in overcoming chemoresistance, but limited by the lack of identification of chemoresistance targets from cancer patients. In the present study, we enrolled chemotherapy-resistant or sensitive CRC patients and used the next-generation RNA sequencing to reveal that Asporin (ASPN) is highly expressed in tumor tissues from oxaliplatin (OXA)-resistant patients and closely correlated with a poor prognosis of CRC. Downregulation of ASPN reversed OXA resistance and promoted cell apoptosis both in vitro and in vivo. To overcome ASPN-mediated OXA resistance, we constructed a nanoparticle-based co-delivery system (denoted as PPO-siASPN) for simultaneous delivery of OXA and siRNA targeting ASPN (siASPN). PPO-siASPN not only facilitated the intracellular delivery of OXA through the enhanced cellular uptake, but effectively suppressed ASPN expression for synergistic antitumor activity in vitro and in vivo. In the more clinically relevant patient-derived xenograft (PDX) mouse model, systemic administration of PPO-siASPN achieved a remarkable therapeutic effect. This study uncovered the critical role of ASPN in causing OXA resistance in CRC patients and suggests a promising nanoformulation that may be more effective than current standard-of-care medications.

Low-dose orlistat promotes the therapeutic effect of oxaliplatin in colorectal cancer.

The failure of and resistance to oxaliplatin (OXA)-based chemotherapies may lead to poor prognosis in colorectal cancer (CRC) patients. It has been reported that orlistat (Orli) exhibits potent antitumor effects in several malignant tumors. Here, we identified that OXA in combination with low-dose Orli could sensitize CRC cells to OXA and induce marked synergistic apoptosis in vitro and in vivo. The potential synergistic effects were confirmed and quantified by in silico analysis. Furthermore, we validated the synergistic anti-tumor effects in CRC PDX mice model. A qPCR array was performed to evaluate the changes in 85 apoptosis-related genes to elucidate the possible molecular mechanisms in combination-induced cytotoxicity. To conclude, the antitumor synergistic effects of OXA and Orli make them effective and promising candidates for cancer treatment.

Pan-Cancer Analysis Reveals SH3TC2 as an Oncogene for Colorectal Cancer and Promotes Tumorigenesis via the MAPK Pathway.

SH3 domain and tetrapeptide repeat 2 (SH3TC2) is a protein-encoding gene and has previously been described as a critical signaling hub for neurological disorders. Although increasing evidence supports a vital role of SH3TC2 in the tumorigenesis of various kinds of cancer, no systematic analysis of SH3TC2 is available. The function and mechanism of SH3TC2 in other cancers remain unknown. Thus, this study aimed to analyze SH3TC2 in various kinds of cancer to find its tumorigenic role in one or more specific cancers. In the current study, we analyzed the expression level and prognostic value of SH3TC2 in different tumors in the TCGA-GTEx pan-cancer dataset. Subsequently, the prognostic role and mechanism of SH3TC2 in colorectal cancer (CRC) were further explored via clinical samples and in vitro and in vivo experiments. We observed differential expression of SH3TC2 in colon adenocarcinoma (COAD), acute myeloid leukemia (LAML), READ (rectum adenocarcinoma), SKCM (skin cutaneous melanoma), and TGCT (testicular germ cell tumors). Subsequently, SH3TC2 showed a significant effect on the clinical stage and prognostic value in CRC, LAML, and SKCM. Moreover, we found in the TCGA database and seven GEO datasets that SH3TC2 was significantly highly expressed in tumor tissue. Through enrichment analysis of SH3TC2 and its co-expressed genes, we found that SH3TC2 may play a role in the MAPK signaling pathway. Correlation analysis indicated that SH3TC2 was significantly associated with multiple key factors in the MAPK signaling pathway. Additionally, higher expression of SH3TC2 was found in tumor tissue in our cohort including 40 CRC patients. Overexpression of SH3TC2 may imply poor prognosis. Knockdown of SH3TC2 significantly inhibited tumor invasion, migration, and proliferation. More importantly, knockdown of SH3TC2 inhibited tumor growth in a CRC mouse model. The study preliminarily conducted a pan-cancer study of SH3TC2 and further explored the mechanism of SH3TC2 in CRC. Our research revealed that higher expression of SH3TC2 may promote CRC progression and invasion via the MAPK signaling pathway.

Corrigendum: Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer.

[This corrects the article DOI: 10.3389/fonc.2022.827891.].

Fluorescence turn-on Cu2-xSe@HA-rhodamine 6G FRET nanoprobe for hyaluronidase detection and imaging.

The application of nanostructures to design fluorescence resonance energy transfer (FRET) based sensing platforms has been greatly concerned with the demand for sensitive and selective detection of biomolecules. Here, a novel sensitive turn-on fluorescence strategy based on the FRET mechanism has been designed for hyaluronidase (HAase) detection through the modulation of Cu2-xSe@HA-Rh6G nanoprobe fabricated by self-assembly of rhodamine 6G (Rh6G) together with Cu2-xSe@HA nanoparticles through electrostatic adsorption. The Cu2-xSe@HA had extensive localized surface plasma resonance (LSPR) absorption in the wide range of ultraviolet (UV) to near-infrared (NIR) wavelengths and showed good light capture characteristics, which can be acted as good acceptors in the FRET interactions with Rh6G, inducing its efficient fluorescence quenching. In the presence of HAase, the FRET process was disrupted and the fluorescence signal was recovered. In the range of 0.1-10.0 U/mL, the fluorescence recovery of Rh6G showed a good linear relationship with the concentration of HAase, and the detection limit was 0.06 U/mL. The sensing platform has been used for HAase detection in real urine samples and cancer cells imaging.

Effects of Preoperative Radiotherapy on Long-Term Bowel Function in Patients With Rectal Cancer Treated With Anterior Resection: A Systematic Review and Meta-analysis.

Background: Anterior resection is a common surgical approach used in rectal cancer surgery; however, this procedure is known to cause bowel injury and dysfunction. Neoadjuvant therapy is widely used in patients with locally advanced rectal cancer. In this study, we determined the effect of preoperative radiotherapy on long-term bowel function in patients who underwent anterior resection for treatment of rectal cancer. Methods: We performed a comprehensive literature search of the PubMed, Embase, Web of Science, and the Cochrane Library databases. A random-effects model was used in the meta-analysis by the Review Manager software, version 5.3. Results: This systematic review and meta-analysis included 12 studies, which used low anterior resection syndrome score with a total of 2349 patients. Based on them, we concluded that low anterior resection syndrome was significantly more common in the preoperative radiotherapy group (odds ratio 3.59, 95% confidence interval 2.68-4.81, P < .00001) and that major low anterior resection syndrome also occurred significantly more frequently in the preoperative radiotherapy group (odds ratio 3.28, 95% confidence interval 2.05-5.26, P < .00001). Subgroup analyses of long-course radiation, total mesorectal excision, and non-metastatic tumors were performed, and the results met the conclusions of the primary outcomes. Conclusions: Preoperative radiotherapy negatively affects long-term bowel function in patients who undergo anterior resection for rectal cancer.

Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer.

Chemotherapy resistance represents a formidable obstacle in advanced or metastatic colorectal cancer (CRC) patients. It is reported that ATPase copper transporting alpha (ATP7A) plays an important role in chemotherapy resistance in CRC. Here, we identified ATP7A as a potentially key gene of OXA resistance in CRC. The patients with higher expression of ATP7A tended to have platinum drug resistance. While the lower expression of ATP7A by siRNA knockdown resulted in enhancement of OXA sensitivity and increased OXA-induced apoptosis. Further, we demonstrated a novel and safe strategy to increase CRC chemosensitivity by delivering siRNA into tumor cells via a novel nanoparticle, DAN. In summary, our study provided a novel nanocarrier-based delivery of ATP7A to interfere in a key gene of chemo-resistance in CRC, which may be a novel therapeutic strategy to overcome chemotherapy resistance in CRC.

One-component nano-metal-organic frameworks with superior multienzyme-mimic activities for 1,4-dihydropyridine metabolism.

Although a number of nanozymes have been developed, it is still difficult to develop single-component nanozyme with overall high multienzyme-like activities. In this study, the nanosized metal-organic frameworks (nano-MOFs) FePCN (PCN stands for porous coordination network) was synthesized by integrating zirconium and iron ions with different catalytic property on single-component MOFs and exhibited superior intrinsic multienzyme-like activities, namely oxidase-, peroxidase- and phosphatase-mimicking activity. The catalytic active sites of oxidase- and peroxidase-, and phosphatase-like activity of FePCN were Fe-centers and Zr-O clusters, respectively. Based on the intrinsic oxidase-like activity and the similarity of molecular structures between cytochrome P450 oxidase (CYP) cofactors and the organic linker in FePCN, FePCN exhibited high CYP-like activity to catalyze the oxidation of hypotensive drug 1,4-dihydropyridine (1,4-DHP) into diethyl 2,6-dimethylpyridine-3,5-dicarboxylate (DDPD) and the yield of DDPD reached over 80%. Moreover, as peroxidase- and phosphatase-mimics, FePCN was successfully applied to detecting H2O2 under neutral condition and catalyzing the dephosphorylation of adenosine triphosphate (ATP), respectively. This study provides a feasible way for rational design one-component nanomaterials as multienzyme-mimics.