Journal: Bioactive Materials

Article Title: A dual-targeting strategy to inhibit colorectal cancer liver metastasis via tumor cell ferroptosis and cancer-associated fibroblast reprogramming

doi: 10.1016/j.bioactmat.2025.05.025

Figure Lengend Snippet: Illustration of the mechanism by which CCM-FSS&CHM-ABI remolds CAFs and induces ferroptosis.

Article Snippet: CCM-FSS&CHM-ABI simultaneously targets both components by integrating: (1) a tumor cell membrane-encapsulated ferroptosis inducer (CCM-FSS) that enhances lipid peroxidation and oxidative stress in CXCR4 + /GPX4 + tumor cells, leading to ferroptotic cell death, and (2) a hybrid cancer cell–CAF membrane-coated CXCR4–NOX4 inhibitor (CHM-ABI) that suppresses CAF activation, reducing TGF-β and CXCL12 signaling to remodel the TME.

Techniques:

Journal: Bioactive Materials

Article Title: A dual-targeting strategy to inhibit colorectal cancer liver metastasis via tumor cell ferroptosis and cancer-associated fibroblast reprogramming

doi: 10.1016/j.bioactmat.2025.05.025

Figure Lengend Snippet: Single-cell transcriptome analysis reveals that CAFs promote tumor progression. (A) UMAP view of 6 CRC cell subpopulations. (B) CRC cell subpopulation composition across different groups. (C) Expression levels of cell migration signature across CRC cell subpopulations. (D) Gene Set Enrichment Analysis (GSEA) of ferroptosis and immunogenic cell death associated with CXCR4 + GPX4 + CRC subpopulation. (E) RFS outcomes of CRC patients with low and high CXCR4 expression. (F) Overall survival (OS) outcomes of CRC patients with low and high GPX4 expression. (G) UMAP view of 6 fibroblast subpopulations. (H) Expression levels of CAFs-related marker genes. (I) Fibroblast subpopulation composition across different groups. (J) Signaling pathways associated with NOX4 + TGFB1 + CXCL12 + CAFs subpopulation. (K) GSEA of ferroptosis and immunogenic cell death associated with CXCR4 + GPX4 + CRC subpopulation. (L–M) Recurrence-free survival (RFS) and OS outcomes of CRC patients with low and high NOX4 expression. (N) Number of receptor-ligand pairs between NOX4 + TGFB1 + CXCL12 + CAFs subpopulation and CRC cell subpopulations. (O) Cytokine communication between NOX4 + TGFB1 + CXCL12 + CAFs subpopulation and CRC cell subpopulations.

Article Snippet: CCM-FSS&CHM-ABI simultaneously targets both components by integrating: (1) a tumor cell membrane-encapsulated ferroptosis inducer (CCM-FSS) that enhances lipid peroxidation and oxidative stress in CXCR4 + /GPX4 + tumor cells, leading to ferroptotic cell death, and (2) a hybrid cancer cell–CAF membrane-coated CXCR4–NOX4 inhibitor (CHM-ABI) that suppresses CAF activation, reducing TGF-β and CXCL12 signaling to remodel the TME.

Techniques: Expressing, Migration, Marker, Protein-Protein interactions

Journal: Bioactive Materials

Article Title: A dual-targeting strategy to inhibit colorectal cancer liver metastasis via tumor cell ferroptosis and cancer-associated fibroblast reprogramming

doi: 10.1016/j.bioactmat.2025.05.025

Figure Lengend Snippet: Explored the effects of CCM-FSS&CHM-ABI on ferroptosis and immunity-related factors in CT26 cells. (A) In vitro measurement of MDA content of CT26 cells in CT26-CAFs cell co-culture system (n = 3). (B) In vitro determination of ROS content of CT26 cells in CT26-CAFs cell co-culture system (n = 3). (C) In vitro determination of GSH content of CT26 cells in CT26-CAFs cell co-culture system (n = 3). (D) In vitro calculation of Fe (II) of CT26 cells within CT26-CAFs cell co-culture system, and (E) its quantification (n = 3). (F) In vitro mitochondrial morphology under biological electron microscopy of CT26 cells in CT26-CAFs cell co-culture system. (G) Bivariate JC-1 dye analysis of the mitochondrial membrane potential in CT26 cells was performed using flow cytometry (n = 3). (H) In vitro Western Blotting results for GPX4 and ALOX12 of CT26 cells in CT26-CAFs cell co-culture system, and (I–J) its quantification (n = 3). (K) In vitro determination of extracellular ATP content in CT26 cells (n = 3). (L) In vitro expression of HMGB1 and CRT of CT26 cells in CT26-CAFs cell co-culture system, and (M–N) their quantification (n = 3). (O) Flow cytometry analysis for DC cell in vitro , and (Q) their quantification (n = 3). (P) Flow cytometry analysis for TAM in vitro , and (R) their quantification (n = 3). (S) Scheme of the molecular mechanism inducing ferroptosis and silence CAFs to promote immune activation by CCM-FSS&CHM-ABI (the schematic diagram was created by Biorender).

Article Snippet: CCM-FSS&CHM-ABI simultaneously targets both components by integrating: (1) a tumor cell membrane-encapsulated ferroptosis inducer (CCM-FSS) that enhances lipid peroxidation and oxidative stress in CXCR4 + /GPX4 + tumor cells, leading to ferroptotic cell death, and (2) a hybrid cancer cell–CAF membrane-coated CXCR4–NOX4 inhibitor (CHM-ABI) that suppresses CAF activation, reducing TGF-β and CXCL12 signaling to remodel the TME.

Techniques: In Vitro, Co-Culture Assay, Electron Microscopy, Membrane, Flow Cytometry, Western Blot, Expressing, Activation Assay

Journal: Bioactive Materials

Article Title: A dual-targeting strategy to inhibit colorectal cancer liver metastasis via tumor cell ferroptosis and cancer-associated fibroblast reprogramming

doi: 10.1016/j.bioactmat.2025.05.025

Figure Lengend Snippet: Evaluation of the in vivo distribution, therapeutic effects, and influence on ferroptosis, CAFs reprogramming, and immunity-related factors of CCM-FSS&CHM-ABI in the orthotopic CT26 tumor-bearing mouse model. (A) Protocol for establishing orthotopic CT26 tumor-bearing mouse model (the schematic diagram was created by Biorender). (B) In vivo drug distribution in the orthotopic tumor-bearing model in mice. (C) Dosage regimen in the orthotopic CT26 tumor-bearing mouse model. (D) In vivo tumor size in the orthotopic tumor-bearing mouse model. (E) In vivo expression of HMGB1 and CRT in tumors of the mouse in the orthotopic tumor-bearing mouse model. (F) In vivo H&E and expression of TUNEL, Ki-67, GPX4, NOX4, CXCR4, and FAP-α in tumors of the mouse in the liver metastasis CT26 tumor-bearing mouse model. (G) Flow cytometry analysis for DC cell in vivo (n = 3). (H) Flow cytometry analysis for TAM in vivo (n = 3). (I) Flow cytometry analysis for CD8 + T cell in vivo . (J–L) The quantification of flow cytometry analysis (n = 3). (M) In vivo CXCL12, TGF-β, TNF-α, and IFN-γ content in the orthotopic tumor-bearing mouse model (n = 3).

Article Snippet: CCM-FSS&CHM-ABI simultaneously targets both components by integrating: (1) a tumor cell membrane-encapsulated ferroptosis inducer (CCM-FSS) that enhances lipid peroxidation and oxidative stress in CXCR4 + /GPX4 + tumor cells, leading to ferroptotic cell death, and (2) a hybrid cancer cell–CAF membrane-coated CXCR4–NOX4 inhibitor (CHM-ABI) that suppresses CAF activation, reducing TGF-β and CXCL12 signaling to remodel the TME.

Techniques: In Vivo, Expressing, TUNEL Assay, Flow Cytometry

Journal: Bioactive Materials

Article Title: A dual-targeting strategy to inhibit colorectal cancer liver metastasis via tumor cell ferroptosis and cancer-associated fibroblast reprogramming

doi: 10.1016/j.bioactmat.2025.05.025

Figure Lengend Snippet: Evaluate therapeutic effects, and influence on ferroptosis, CAF reprogramming, and immunity-related factors of CCM-FSS&CHM-ABI in the liver metastasis CT26 tumor-bearing mouse model. (A) Protocol for establishing liver metastasis CT26 tumor-bearing mouse model (the schematic diagram was created by Biorender). (B) Dosage regimen in liver metastasis CT26 tumor-bearing mouse model. (C) liver surface nodules, and (D) quantification of the number of liver surface nodules tumor weight in the liver metastasis CT26 tumor-bearing mouse model (n = 5). (E) In vivo expression of HMGB1 and CRT in tumors of the mouse in the liver metastasis CT26 tumor-bearing mouse model. (F) In vivo H&E and expression of TUNEL, Ki-67, GPX4, NOX4, and CXCR4 in tumors of the mouse in the liver metastasis CT26 tumor-bearing mouse model, and (G–K) their quantification (n = 3). (L) In vivo expression of FAP-α in tumors of the mouse in the liver metastasis CT26 tumor-bearing mouse model, and (M) its quantification (n = 3). (N) Flow cytometry for matured DC cells in vivo , and (Q) their quantification (n = 3). (O) Flow cytometry for TAM in vivo , and (R) their quantification (n = 3). (P) Flow cytometry for CD8 + T cells in vivo , and (S) their quantification (n = 3). (T) In vivo CXCL12, TGF-β, TNF-α, and IFN-γ content (n = 3).

Article Snippet: CCM-FSS&CHM-ABI simultaneously targets both components by integrating: (1) a tumor cell membrane-encapsulated ferroptosis inducer (CCM-FSS) that enhances lipid peroxidation and oxidative stress in CXCR4 + /GPX4 + tumor cells, leading to ferroptotic cell death, and (2) a hybrid cancer cell–CAF membrane-coated CXCR4–NOX4 inhibitor (CHM-ABI) that suppresses CAF activation, reducing TGF-β and CXCL12 signaling to remodel the TME.

Techniques: In Vivo, Expressing, TUNEL Assay, Flow Cytometry