Difference of Antrochoanal Polyps Between Children and Adults in the Chinese Population.

OBJECTIVE: This study aims to find the difference in clinical and immunopathological characteristics between children and adults with antrochoanal polyps (ACPs) in the Chinese population. METHODS: The clinical data of 69 patients diagnosed with ACPs were retrospectively analyzed. Cytokine levels in 16 controls and 40 ACPs tissues were determined by quantitative real-time polymerase chain reaction (qPCR). The expression of matrix metalloproteinase (MMP)-9 was measured using qPCR, immunofluorescent staining, and western blot. RESULTS: There were 51 (73.9%) children (<18 years old) and 18 (26.1%) adults (≥18 years old). The sex ratio differed significantly between the two groups (p = 0.0032). There were no significant differences in the nasal side of ACPs and approaches to surgery between the two groups. In both groups, the most common symptom was nasal obstruction, followed by nasal discharge. As for associated nasal diseases, there was a significant difference between the two groups in septal deviation (p = 0.0223). Adult patients showed significantly higher expression of IL-8 mRNA than children (p = 0.0424). The mRNA and protein levels of MMP-9 were also significantly higher in adult patients than in children (p = 0.0498 and 0.0009, respectively). CONCLUSION: In the Chinese population, the comorbidities and immunopathological characteristics of adult ACP patients are different from those of children. The level of IL-8 and MMP-9 was significantly higher in ACPs of adults than in children, which may contribute to the more severe tissue remolding in adult ACP patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2093-2099, 2024.

Exogenous plant growth regulator and foliar fertilizers for phytoextraction of cadmium with Boehmeria nivea [L.] Gaudich from contaminated field soil.

As a enrichment plant, ramie can be used for the phytoremediation of cadmium (Cd)-contaminated soil. However, it is worth exploring the role of plant growth regulators and foliar fertilizers in the process of plant growth and development and Cd adsorption. By measuring the agronomic traits, Cd content of aboveground and underground ramie, calculating the Cd transfer coefficient (TF) and Cd bioconcentration factors (BCF), and the correlation between various indicators. This study examined the effects of plant growth regulators and foliar fertilizers on ramie's capacity for Cd accumulation and transportation. Plant growth regulators and foliar fertilizers increased the Cd content of the aboveground ramie, reduced the Cd content of the underground ramie, and increased the TF. Among them, GA-1 increased the Cd content of the aboveground ramie to 3 times more than that of the control and reduced the Cd content of the underground ramie by 54.76%. Salicylic acid (SA) increased the Cd content of the aboveground ramie to three times more than that of the control. The combination of GA and foliar fertilizer reduced the Cd content of the aboveground and underground ramie and the TF and BCF of the underground ramie. After the hormones were sprayed, the TF of ramie had a significant positive correlation with the Cd content of the aboveground ramie; the BCF of the aboveground ramie had a significant positive correlation with the Cd content and TF of the aboveground ramie. The results indicate that Brassinolide (BR), gibberellin (GA), ethephon (ETH), polyamines (PAs), and salicylic acid (SA) have different effects on the enrichment and transport of Cd in ramie. This study provided an effective method to improve the capacity for ramie to adsorb heavy metals during cultivation.

Hepatocyte CD36 protects mice from NASH diet-induced liver injury and fibrosis via blocking N1ICD production.

BACKGROUND & AIMS: Fatty acid translocase CD36 (CD36/FAT) is a widely expressed membrane protein with multiple immuno-metabolic functions. Genetic CD36 deficiency is associated with increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in patients. Liver fibrosis severity mainly affects the prognosis in patients with MAFLD, but the role of hepatocyte CD36 in liver fibrosis of MAFLD remains unclear. METHODS: A high-fat high-cholesterol diet and a high-fat diet with high-fructose drinking water were used to induce nonalcoholic steatohepatitis (NASH) in hepatocyte-specific CD36 knockout (CD36LKO) and CD36flox/flox (LWT) mice. Human hepG2 cell line was used to investigate the role of CD36 in regulating Notch pathway in vitro. RESULTS: Compared to LWT mice, CD36LKO mice were susceptible to NASH diet-induced liver injury and fibrosis. The analysis of RNA-sequencing data revealed that Notch pathway was activated in CD36LKO mice. LY3039478, an inhibitor of γ-secretase, inhibited Notch1 protein S3 cleavage and Notch1 intracellular domain (N1ICD) production, alleviating liver injury and fibrosis in CD36LKO mice livers. Likewise, both LY3039478 and knockdown of Notch1 inhibited the CD36KO-induced increase of N1ICD production, causing the decrease of fibrogenic markers in CD36KO HepG2 cells. Mechanistically, CD36 formed a complex with Notch1 and γ-secretase in lipid rafts, and hence CD36 anchored Notch1 in lipid rafts domains and blocked Notch1/γ-secretase interaction, inhibiting γ-secretase-mediated cleavage of Notch1 and the production of N1ICD. CONCLUSIONS: Hepatocyte CD36 plays a key role in protecting mice from diet-induced liver injury and fibrosis, which may provide a potential therapeutic strategy for preventing liver fibrogenesis in MAFLD.

Anti-Inflammatory Polyketide Derivatives from the Sponge-Derived Fungus Pestalotiopsis sp. SWMU-WZ04-2.

Five undescribed polyketide derivatives, pestaloketides A-E (1-5), along with eleven known analogues (6-16), were isolated from the sponge-derived fungus Pestalotiopsis sp. Their structures, including absolute configurations, were elucidated by analyses of NMR spectroscopic HRESIMS data and electronic circular dichroism (ECD) calculations. Compounds 5, 6, 9, and 14 exhibited weak cytotoxicities against four human cancer cell lines, with IC50 values ranging from 22.1 to 100 µM. Pestaloketide A (1) is an unusual polyketide, featuring a rare 5/10/5-fused ring system. Pestaloketides A (1) and B (2) exhibited moderately inhibited LPS-induced NO production activity, with IC50 values of 23.6 and 14.5 µM, respectively, without cytotoxicity observed. Preliminary bioactivity evaluations and molecular docking analysis indicated that pestaloketides A (1) and B (2) had the potential to be developed into anti-inflammatory activity drug leads.

Expression of DOG1 in peripheral blood cells of patients with gastrointestinal stromal tumor.

BACKGROUND AND STUDY AIMS: The diagnosis and surveillance of gastrointestinal stromal tumor (GIST) rely on pathology and immunochemistry (IHC), making it complicated and invasive. Noninvasive and convenient biomarkers of this disease need to be explored. The high specificity and sensitivity of IHC in detecting GIST 1 (DOG1) in biopsy indicate that it is also expressed in circulating tumor cells of the blood and may be an ideal biomarker for GIST. This aimed to detect the expression of DOG1 in peripheral blood cells (PBCs) and determine the relationship between DOG1 expression and clinical factors. PATIENTS AND METHODS: A total of 45 patients with GIST and 46 healthy controls (HCs) were recruited from the Second Affiliated Hospital of Nanchang University between December 2015 and June 2018. PBCs were isolated from peripheral venous blood by density gradient centrifugation. RNA was extracted from PBCs, and DOG1 mRNA was detected by quantitative reverse transcription polymerase chain reaction. DOG1 mRNA expression between GIST and HC was compared, and the relationship between clinical factors and DOG1 was also analyzed. RESULTS: DOG1 mRNA expression in PBCs was significantly higher in patients with GIST than that in HCs (3.326 [1.942-5.328] versus 0.744 [0.269-1.087], p < 0.01). The specificity and sensitivity were 88.9% and 89.1%, respectively (AUC = 0.912). Tumor diameter and risk of aggressive behavior were correlated with DOG1 expression, and other clinical factors (sex, age, location, number of phase-splitting cells, Ki-67 index, metastatic status) did not show any relationship with DOG1 expression. However, clinical factors, including tumor diameter and risk grade, were not independent factors in DOG1 expression when multivariate analysis was conducted. CONCLUSION: DOG1 expressions were significantly higher in patients with GIST than that in HCs. Tumor diameter and risk classification correlated with DOG1 expression but were not independent factors. DOG1 in PBCs is a promising noninvasive biomarker for GIST.

Inhibition of ELF3 confers synthetic lethality of PARP inhibitor in non-small cell lung cancer.

BACKGROUND: E74 Like ETS Transcription Factor 3 (ELF3) functions as a transcriptional factor to regulate non-small cell lung cancer (NSCLC) differentiation and progression. Poly(ADP-ribose) polymerase (PARP) inhibitors demonstrate anti-tumor effect in NSCLC. This study aimed to investigate whether ELF3 confers synthetic lethal with PARP inhibitor in NSCLC. MATERIALS AND METHODS: The sensitivity of PARP inhibitor, Olaparib, to different NSCLC cell lines was determined by half maximal inhibitory concentration (IC50). Expression of ELF3 in NSCLC cell lines was evaluated by western blot. The effects of ELF3 on cytotoxicity of Olaparib to NSCLC were investigated by MTT (3-(4,5- di methyl thiazol -2-yl)-2,5-di phenyl tetrazolium bromide) and colony formation assays. The underlying mechanism involved in synthetic lethality with ELF3 and PARP inhibitors in NSCLC were detected by immunofluorescence and Western blot. RESULTS: ELF3 was up-regulated in NSCLC cell lines exhibiting resistance to PARP inhibitor, Olaparib. Knock down of ELF3 decreased the sensitivity and enhanced cytotoxicity of Olaparib to NSCLC cells. Moreover, knock down of ELF3 increased S139 phosphorylated histone H2AX (γH2AX), and inhibited homologous recombination activity via down-regulation of DNA repair protein RAD51 homolog 1 (RAD51), thus showing deficiency in DNA damage repair. Over-expression of ELF3 could up-regulate phosphorylation of AKT (Protein kinase B), while knock down of ELF3 regulated homologous recombination-mediated DNA repair via down-regulation of phosphorylation of AKT. CONCLUSION: Knock down of ELF3 revealed homologous recombination deficiency via AKT signaling pathway, and synthetic lethality with ELF3 inhibition and PARP inhibitor indicated the clinical significance of PARP inhibitor in ELF3-deficient NSCLC.

Pyrido[2, 3-d]pyrimidin-7(8H)-ones as new selective orally bioavailable Threonine Tyrosine Kinase (TTK) inhibitors.

A series of pyrido [2, 3-d]pyrimidin-7(8H)-ones were designed and synthesized as new selective orally bioavailable Threonine Tyrosine Kinase (TTK) inhibitors. One of the representative compounds, 5o, exhibited strong binding affinity with a Kd value of 0.15 nM, but was significantly less potent against a panel of 402 wild-type kinases at 100 nM. The compound also potently inhibited the kinase activity of TTK with an IC50 value of 23 nM, induced chromosome missegregation and aneuploidy, and suppressed proliferation of a panel of human cancer cell lines with low µM IC50 values. Compound 5o demonstrated good oral pharmacokinetic properties with a bioavailability value of 45.3% when administered at a dose of 25 mg/kg in rats. Moreover, a combination therapy of 5o with paclitaxel displayed promising in vivo efficacy against the HCT-116 human colon cancer xenograft model in nude mice with a Tumor Growth Inhibition (TGI) value of 78%. Inhibitor 5o may provide a new research tool for further validating therapeutic potential of TTK inhibition.

GZD824 as a FLT3, FGFR1 and PDGFRα Inhibitor Against Leukemia In Vitro and In Vivo.

GZD824 is a novel third-generation BCR-ABL inhibitor. It entered Phase II clinical trials in China and Phase Ib clinical trials in USA in 2019 for treatment of patients with resistant chronic myeloid leukemia (CML). We found that at concentrations below 10 nM, GZD824 significantly suppresses FLT3, FGFR1 and PDGFRα kinase activities and inhibits their signal pathways in MV4-11Flt3-ITD, KG-1FGFR1OP2-FGFR1 and EOL-1FIP1L1-PDGFRa leukemia cells. It selectively inhibits the growth of MV4-11Flt3-ITD, KG-1FGFR1OP2-FGFR1 and EOL-1FIP1L1-PDGFRa cells, and also effectively suppresses the growth of Ba/F3-FLT3-ITD cells harboring F691I and other mutations with IC50 values <10 nM. GZD824 induces G0/G1 phase arrest and apoptosis in MV4-11, KG-1 and EOL-1 cells and activates cleavage of caspase-3 and PARP. In MV4-11, Ba/F3-ITD-F691I and KG-1 mouse xenograft models, GZD824 at 10 or 20 mg/kg, q2d, p.o. almost completely eradicates tumors. It also inhibits the viability of primary leukemic blasts from a FLT3-ITD positive AML patient but not those expressing native FLT3. Thus GZD824 suppresses leukemia cells of FLT3-ITD-driven AML and other hematologic malignancies driven by FGFR1 or PDGFRa, and it may be considered to be a novel agent for the treatment of leukemia.

Design and Optimization of 3'-(Imidazo[1,2-a]pyrazin-3-yl)-[1,1'-biphenyl]-3-carboxamides as Selective DDR1 Inhibitors.

DDR1 is considered as a promising target for cancer therapy, and selective inhibitors against DDR1 over other kinases may be considered as promising therapeutic agents. Herein, we have identified a series of 3'-(imidazo[1,2-a]pyrazin-3-yl)-[1,1'-biphenyl]-3-carboxamides as novel selective DDR1 inhibitors. Among these, compound 8v potently inhibited DDR1 with an IC50 of 23.8 nM, while it showed less inhibitory activity against DDR2 (IC50 = 1740 nM) and negligible activities against Bcr-Abl (IC50 > 10 µM) and c-Kit (IC50 > 10 µM). 8v also exhibited excellent selectivity in a KINOMEscan screening platform with 468 kinases. This compound dose-dependently suppressed NSCLC cell tumorigenicity, migration, and invasion. Collectively, these studies support its potential application for treatment of NSCLC.

Design, Synthesis, and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as New Selective Leucine-Zipper and Sterile-α Motif Kinase (ZAK) Inhibitors.

ZAK is a new promising target for discovery of drugs with activity against antihypertrophic cardiomyopathy (HCM). A series of 1,2,3-triazole benzenesulfonamides were designed and synthesized as selective ZAK inhibitors. One of these compounds, 6p binds tightly to ZAK protein (Kd = 8.0 nM) and potently suppresses the kinase function of ZAK with single-digit nM (IC50 = 4.0 nM) and exhibits excellent selectivity in a KINOMEscan screening platform against a panel of 403 wild-type kinases. This compound dose dependently blocks p38/GATA-4 and JNK/c-Jun signaling and demonstrates promising in vivo anti-HCM efficacy upon oral administration in a spontaneous hypertensive rat (SHR) model. Compound 6p may serve as a lead compound for new anti-HCM drug discovery.

2-Amino-2,3-dihydro-1H-indene-5-carboxamide-Based Discoidin Domain Receptor 1 (DDR1) Inhibitors: Design, Synthesis, and in Vivo Antipancreatic Cancer Efficacy.

A series of 2-amino-2,3-dihydro-1H-indene-5-carboxamides were designed and synthesized as new selective discoidin domain receptor 1 (DDR1) inhibitors. One of the representative compounds, 7f, bound with DDR1 with a Kd value of 5.9 nM and suppressed the kinase activity with an half-maximal (50%) inhibitory concentration value of 14.9 nM. 7f potently inhibited collagen-induced DDR1 signaling and epithelial-mesenchymal transition, dose-dependently suppressed colony formation of pancreatic cancer cells, and exhibited promising in vivo therapeutic efficacy in orthotopic mouse models of pancreatic cancer.

Rational design, synthesis and biological evaluation of ubiquinone derivatives as IDO1 inhibitors.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an attractive therapeutic target for the treatment of cancer, chronic viral infections and neurological disorders characterized by pathological immune stimulation. Herein, a series of known metal-chelating ubiquinone derivatives were designed, synthesized and evaluated for the IDO1 inhibiting activities. The docking studies showed that the compounds 11, 16, 18 and coenzyme-Q1 exhibited different binding modes to IDO1 protein. Among these compounds, the most active compound is 16d with an IC50 of 0.13 µM in enzymatic assay. The results reveal that a possible halogen bonding interaction between the bromine atom (3-Br) and Cys129 significantly enhances the inhibition activity against IDO1. This study provides structural insights of the interactions between ubiquinone analogues and IDO1 protein for the further modification and optimization.

Quinolone antibiotic derivatives as new selective Axl kinase inhibitors.

Axl is a new promising molecular target for antineoplastic therapies. A series of quinolone antibiotic derivatives were designed and synthesized as new selective Axl inhibitors. One of the most promising compound 8i bound tightly to Axl with a Kd value of 1.1 nM, and inhibited its kinase activity with an IC50 value of 26 nM. The compound also significantly inhibited the phosphorylation of Axl and dose dependently inhibited cell invasion and migration in TGF-ß1 induced MDA-MD-231 breast cancer cells. In addition, 8i demonstrated reasonable pharmacokinetic properties and exhibited extraordinary target selectivity over 468 kinases except for Flt3 (IC50 = 50 nM)), with a S(10) and S(35) value of 0.022 and 0.42 at 1.0 µM, respectively. Compound 8i may serve as a new valuable lead compound for future anticancer drug discovery.

GZD2202, a novel TrkB inhibitor, suppresses BDNF-mediated proliferation and metastasis in neuroblastoma models.

Collective data suggest tropomyosin-related kinase B (TrkB), which is correlated with the growth, migration and poor prognosis of neuroblastoma (NB), is a potential target for NB target therapy. Several Phase I/II pan-Trk inhibitors display impressive clinical outcomes but still no drug has been approved for general use. In this paper, we report a novel structural TrkB inhibitor GZD2202, a structural derivative of our previously identified DDR1 antagonists. GZD2202 demonstrates a moderate selectivity between Trk B/C and TrkA. GZD2202 suppresses the brain-derived neurotrophic factor (BDNF) -mediated TrkB signalling pathway, proliferation, migration and invasion in SH-SY5Y-TrkB neuroblastoma cells, and causes about 36.1% growth inhibition in a SH-SY5Y-TrkB neuroblastoma xenograft model.

Dual targeting delivery of miR-328 by functionalized mesoporous silica nanoparticles for colorectal cancer therapy.

Aim: We aim to explore the regulatory mechanism of miR-328 and further develop miR-328-loaded mesoporous silica nanoparticles (MSNs) and surface-decorated with polymerized dopamine, epithelial cell adhesion molecule aptamer and bevacizumab for the dual-targeting treatment of colorectal cancer (CRC). Materials & methods: The relationship between miR-328 and CPTP and the mechanism and antitumor effect of MSNs-miR-328@PDA-PEG-Apt-Bev were evaluated. Results: We found CPTP is a direct target of miR-328. Compared with other groups, MSNs-miR-328@PDA-PEG-Apt-Bev can significantly increase the level of miR-328 and inhibit the expression of CPTP in SW480 cells. The results exhibit this multifunctional bioconjugates can achieve an increased binding ability and much higher cytotoxicity to CRC both in vitro and in vivo. Conclusion: This multifunctional nanoplatform is a promising miRNA replacement therapy for CRC.

Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2- a]pyrazin-3-ylethynyl)-4-isopropyl- N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2.

Discoidin-domain receptors 1 and 2 (DDR1 and DDR2) are new potential targets for anti-inflammatory-drug discovery. A series of heterocycloalkynylbenzimides were designed and optimized to coinhibit DDR1 and DDR2. One of the most promising compounds, 5n, tightly bound to DDR1 and DDR2 proteins with Kd values of 7.9 and 8.0 nM; potently inhibited the kinases with IC50 values of 9.4 and 20.4 nM, respectively; and was significantly less potent for a panel of 403 wild-type kinases at 1.0 µM. DDR1- and DDR2-kinase inhibition by 5n was validated by Western-blotting analysis in primary human lung fibroblasts. The compound also dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin 6 (IL-6) release in vitro and exhibited promising in vivo anti-inflammatory effects in an LPS-induced-acute-lung-injury (ALI) mouse model. Compound 5n may serve as a lead compound for new anti-inflammatory drug discovery.

Design, Synthesis, and Structure-Activity Relationship Study of 2-Oxo-3,4-dihydropyrimido[4,5- d]pyrimidines as New Colony Stimulating Factor 1 Receptor (CSF1R) Kinase Inhibitors.

Colony stimulating factor 1 receptor kinase (CSF1R) is a well validated molecular target for anticancer drug discovery. Herein, we report the design, synthesis, and structure-activity relationship study of 2-oxo-3,4-dihydropyrimido[4,5- d]pyrimidines as new orally bioavailable CSF1R inhibitors. One of the most promising compounds, 3bw, potently inhibits CSF1R kinase with an IC50 value of 3.0 nM, while it is less potent against structurally related epidermal growth factor receptor (EGFR) and other kinases. The kinase inhibition of 3bw was further validated by Western blotting analysis in RAW264.7 macrophages. The molecule also potently blocks macrophage infiltration, abrogates the protumorigenic influences of macrophages, and exhibits reasonable pharmacokinetic profile. Compound 3bw may serve as a new valuable lead compound for future anticancer drug discovery.

YL143, a novel mutant selective irreversible EGFR inhibitor, overcomes EGFRL858R, T790M -mutant resistance in vitro and in vivo.

YL143 was identified as a novel wild-type sparing EGFRT790M inhibitor with good pharmacokinetic properties. It potently suppresses EGFRL858R/T790M with an 50% inhibitory concentration (IC50 ) value of 2.0 ± 0.3 nmol/L, but is approximately 92-folds less potent against EGFRWT kinase. YL143 suppresses cellular proliferation and induces G0/G1 phase arrest and apoptosis in H1975 cells with EGFRL858R/T790M mutation at 30 nmol/L. It also exhibits acceptable pharmacokinetics (PK) parameters with an oral bioavailability value of 25.0% after oral administration in rats and exhibits promising antitumor efficacy in a gefitinib-resistant human H1975 xenografted model after oral administration of 30 mg/kg/day. These data supported that YL143 could be a promising lead compound for overcoming clinical EGFRT790M resistance of patients with non-small-cell lung cancer (NSCLC).

Design, synthesis, and biological evaluation of novel highly selective polo-like kinase 2 inhibitors based on the tetrahydropteridin chemical scaffold.

Polo-like kinase 2 (Plk2) is a potential target for the treatment of cancer, which displays an important role in tumor cell proliferation and survival. In this report, according to the analysis of critical amino acid residue differences among Plk1, Plk2 and Plk3, and structure-based drug design strategies, two novel series of selective Plk2 inhibitors based on tetrahydropteridin chemical scaffold were designed and synthesized to target two specific residues, Lys86 and Tyr161 of Plk2. All compounds were evaluated for their inhibitory activity against Plk1-Plk3 and the cellular inhibition activity on six different human cancer cell lines. All efforts led to the identification of the most potent compounds C2 (3.40 nM against Plk2) and C21 (4.88 nM against Plk2) from the first and second series of selective Plk2 inhibitors respectively. Additionally, the selectivity of C21 over Plk1/3 was significantly increased with the selectivity indexes of 12.57 and 910.06. Moreover, most of our compounds exhibited antitumor activity in the nanomolar range in the MTT assay, indicating that our compounds, especially C2 and C21 could be promising Plk2 inhibitors for further anticancer research.

EpCAM aptamer-functionalized polydopamine-coated mesoporous silica nanoparticles loaded with DM1 for targeted therapy in colorectal cancer.

DM1, a maytansine derivative, is a highly potential cytotoxic agent but with severe side effects; therefore, its application in clinical cancer therapy is limited. Here, in order to mitigate this intrinsic drawback of DM1, we developed mesoporous silica nanoparticles (MSNs) loaded with DM1 and surface-decorated with hydrochloride dopamine (PDA), polyethylene glycol (PEG), and epithelial cell adhesion molecule (EpCAM) aptamer (APt) for the targeted treatment of colorectal cancer (CRC). In this system, the PDA coating could be used as pH-sensitive gatekeepers to control the release of DM1 from MSNs in response to the pH stimulus and EpCAM APt-guided active targeting enables the increased delivery of DM1 to CRC as well as a reduction in toxicity and side effects by minimizing the exposure of normal tissues to DM1. Results demonstrated that DM1 inhibited the formation of microtubules and induced apoptosis in tumor cells via caspase signaling. In comparison with the control groups, the MSNs-DM1@PDA-PEG-APt bioconjugates exhibited increased binding ability and much higher cytotoxicity to the CRC SW480 cell line. Furthermore, in vivo assays confirmed the advantages of such a strategy. These findings suggested that MSNs-DM1@PDA-PEG-APt could represent a promising therapeutic platform for EpCAM-positive CRC.