Journal: Materials Today Bio

Article Title: Targeting FN1 to overcome gemcitabine resistance in gallbladder cancer: Mechanistic insights and an iRGD-modified PEG-PLGA nanoparticle delivery strategy

doi: 10.1016/j.mtbio.2026.102877

Figure Lengend Snippet: Preparation and characterization of iRGD-NPs (si-FN1). Note: (A) Schematic of iRGD-NPs (si-FN1) synthesis; (B-C) NP size distribution curve and size statistics for iRGD-NPs (si-FN1); (D) ζ-potential of iRGD-NPs (si-FN1); (E) Representative TEM image of iRGD-NPs (si-FN1), Scale bars = 500 nm; (F) RNA agarose gel electrophoresis assessing the EE% of si-FN1; (G) Agarose gel electrophoresis testing the stability of Free si-FN1 and iRGD-NPs (si-FN1) under RNase treatment; (H) Agarose gel electrophoresis testing the stability of Free si-FN1 and iRGD-NPs (si-FN1) incubated at ambient temperature in 25% FBS for 0, 2, 6, and 24 h, followed by treatment with heparin (1000 I.U./mL) for 1 h; (I) DLS measurement of particle size changes of iRGD-NPs (si-FN1) incubated at ambient temperature in 25% FBS for 0, 2, 6, 24, 48, and 72 h; (J) PDI values of the nanoparticle formulations determined by DLS; (K) Characterization of nanoparticle chemical functional groups using Fourier transform infrared spectroscopy. Experiments were repeated three times.

Article Snippet: The NPs (si-FN1) were then conjugated with iRGD peptides (HY-P0122, MCE, USA) through the interaction of the Mal group in Mal–PEG–PLGA with thiol groups in the iRGD peptide for 24 h. The molar ratio of NPs (si-FN1) to iRGD used for binding was 4:1.

Techniques: Agarose Gel Electrophoresis, Incubation, Functional Assay, Fourier Transform Infrared Spectroscopy, Spectroscopy

Journal: Materials Today Bio

Article Title: Targeting FN1 to overcome gemcitabine resistance in gallbladder cancer: Mechanistic insights and an iRGD-modified PEG-PLGA nanoparticle delivery strategy

doi: 10.1016/j.mtbio.2026.102877

Figure Lengend Snippet: In vivo biodistribution and in vitro cellular uptake of iRGD-NPs (si-FN1). Note: (A) Schematic of the in vivo biodistribution testing experiment of iRGD-NPs (si-FN1) in nude mice with subcutaneous xenografts; (B) IVIS images of xenograft-bearing mice at 0, 4, 8, 12, and 24 h after injection with Cy5.5-labeled iRGD-NPs (si-FN1) and NPs (si-FN1); (C) Representative IVIS images of xenograft tissues and various organs from mice 24 h after injection with Cy5.5-labeled iRGD-NPs (si-FN1) and NPs (si-FN1), ∗ indicates p < 0.05; (D) Schematic of the in vitro cellular uptake experiment for iRGD-NPs (si-FN1); (E-F) Immunofluorescence staining (E) and FCM (F) assessing the uptake of iRGD-NPs (si-FN1) by GBC-SD/GEM and NOZ/GEM cells, Scale bars = 25 μm; (G) 3D tumor spheroid model assessing the tumor-penetration capability conferred by iRGD modification (Scale bars = 500 μm). experiments repeated three times. Each group consists of 3 nude mice.

Article Snippet: The NPs (si-FN1) were then conjugated with iRGD peptides (HY-P0122, MCE, USA) through the interaction of the Mal group in Mal–PEG–PLGA with thiol groups in the iRGD peptide for 24 h. The molar ratio of NPs (si-FN1) to iRGD used for binding was 4:1.

Techniques: In Vivo, In Vitro, Injection, Labeling, Immunofluorescence, Staining, Modification

Journal: Materials Today Bio

Article Title: Targeting FN1 to overcome gemcitabine resistance in gallbladder cancer: Mechanistic insights and an iRGD-modified PEG-PLGA nanoparticle delivery strategy

doi: 10.1016/j.mtbio.2026.102877

Figure Lengend Snippet: Impact of NPs delivering si-FN1 on drug resistance and immune cell infiltration in GBC-SD/GEM cells. Note: (A) Schematic of the experimental setup for studying the impact of NPs delivering si-FN1 on GBC GEM resistance; (B-C) RT-qPCR (B) and Western Blot (C) analysis of FN1 and PI3K pathway protein expression in GBC-SD/GEM cells treated with NPs (si-FN1) and iRGD-NPs (si-FN1); (D) CCK-8 assay assessing the viability changes in GBC-SD/GEM cells after treatment with NPs (si-FN1) and iRGD-NPs (si-FN1); (E) Clonogenic assay evaluating colony formation in various groups of GBC-SD/GEM and NOZ/GEM cells; (F) FCM analysis of apoptosis in GBC-SD/GEM cells across different groups; (G) FCM analysis of Tregs levels in CD4 + T cells after co-culture with GBC-SD/GEM cells; (H) FCM analysis of M2 and M1 macrophage levels in THP-1 cells after co-culture with GBC-SD/GEM cells; (I) RT-qPCR analysis of IL-10 or CSF-1 expression in CD4 + T or THP-1 cells co-cultured with GBC-SD/GEM cells. ∗ indicates p < 0.05 compared to the NPs (si-NC) group, # indicates p < 0.05 compared to the NPs (si-FN1) group, experiments repeated three times.

Article Snippet: The NPs (si-FN1) were then conjugated with iRGD peptides (HY-P0122, MCE, USA) through the interaction of the Mal group in Mal–PEG–PLGA with thiol groups in the iRGD peptide for 24 h. The molar ratio of NPs (si-FN1) to iRGD used for binding was 4:1.

Techniques: Quantitative RT-PCR, Western Blot, Expressing, CCK-8 Assay, Clonogenic Assay, Co-Culture Assay, Cell Culture

Journal: Materials Today Bio

Article Title: Targeting FN1 to overcome gemcitabine resistance in gallbladder cancer: Mechanistic insights and an iRGD-modified PEG-PLGA nanoparticle delivery strategy

doi: 10.1016/j.mtbio.2026.102877

Figure Lengend Snippet: Impact of NPs delivering si-FN1 on tumorigenesis and the immunosuppressive environment in GBC-SD/GEM cells. Note: (A) Schematic of the in vivo therapeutic efficacy experiment for iRGD-NPs (si-FN1); (B-C) RT-qPCR (B) and Western Blot (C) analysis of FN1 and PI3K pathway protein expression in xenograft tissues from various mouse groups; (D) Post-dissection images of xenograft tumors from different mouse groups; (E) IVIS monitoring of tumor growth in xenograft mice from weeks 1 to 5; (F) Tumor weight statistics of different mouse groups at week 5; (G-H) Immunohistochemistry and TUNEL staining assessing Ki67 protein expression and apoptosis in tumor tissues from various mouse groups (Scale bars = 50 μm); (I) FCM analysis of Tregs infiltration levels in GBC-SD/GEM cell xenograft tissues from different mouse groups; (J) FCM analysis of M2 and M1 macrophage infiltration levels in GBC-SD/GEM cell xenograft tissues from various mouse groups; (K) RT-qPCR analysis of the expression of immunosuppressive factors in GBC-SD/GEM cell xenograft tissues from different mouse groups. ∗ indicates p < 0.05 compared to the NPs (si-NC) + GEM group, # indicates p < 0.05 compared to the NPs (si-FN1) + GEM group, each group consisting of 6 mice.

Article Snippet: The NPs (si-FN1) were then conjugated with iRGD peptides (HY-P0122, MCE, USA) through the interaction of the Mal group in Mal–PEG–PLGA with thiol groups in the iRGD peptide for 24 h. The molar ratio of NPs (si-FN1) to iRGD used for binding was 4:1.

Techniques: In Vivo, Drug discovery, Quantitative RT-PCR, Western Blot, Expressing, Dissection, Immunohistochemistry, TUNEL Assay, Staining

Journal: Materials Today Bio

Article Title: Targeting FN1 to overcome gemcitabine resistance in gallbladder cancer: Mechanistic insights and an iRGD-modified PEG-PLGA nanoparticle delivery strategy

doi: 10.1016/j.mtbio.2026.102877

Figure Lengend Snippet: Preparation and characterization of iRGD-NPs (si-FN1). Note: (A) Schematic of iRGD-NPs (si-FN1) synthesis; (B-C) NP size distribution curve and size statistics for iRGD-NPs (si-FN1); (D) ζ-potential of iRGD-NPs (si-FN1); (E) Representative TEM image of iRGD-NPs (si-FN1), Scale bars = 500 nm; (F) RNA agarose gel electrophoresis assessing the EE% of si-FN1; (G) Agarose gel electrophoresis testing the stability of Free si-FN1 and iRGD-NPs (si-FN1) under RNase treatment; (H) Agarose gel electrophoresis testing the stability of Free si-FN1 and iRGD-NPs (si-FN1) incubated at ambient temperature in 25% FBS for 0, 2, 6, and 24 h, followed by treatment with heparin (1000 I.U./mL) for 1 h; (I) DLS measurement of particle size changes of iRGD-NPs (si-FN1) incubated at ambient temperature in 25% FBS for 0, 2, 6, 24, 48, and 72 h; (J) PDI values of the nanoparticle formulations determined by DLS; (K) Characterization of nanoparticle chemical functional groups using Fourier transform infrared spectroscopy. Experiments were repeated three times.

Article Snippet: The NPs (si-FN1) were then conjugated with iRGD peptides (HY-P0122, MCE, USA) through the interaction of the Mal group in Mal–PEG–PLGA with thiol groups in the iRGD peptide for 24 h. The molar ratio of NPs (si-FN1) to iRGD used for binding was 4:1.

Techniques: Agarose Gel Electrophoresis, Incubation, Functional Assay, Fourier Transform Infrared Spectroscopy, Spectroscopy

Journal: Materials Today Bio

Article Title: Targeting FN1 to overcome gemcitabine resistance in gallbladder cancer: Mechanistic insights and an iRGD-modified PEG-PLGA nanoparticle delivery strategy

doi: 10.1016/j.mtbio.2026.102877

Figure Lengend Snippet: In vivo biodistribution and in vitro cellular uptake of iRGD-NPs (si-FN1). Note: (A) Schematic of the in vivo biodistribution testing experiment of iRGD-NPs (si-FN1) in nude mice with subcutaneous xenografts; (B) IVIS images of xenograft-bearing mice at 0, 4, 8, 12, and 24 h after injection with Cy5.5-labeled iRGD-NPs (si-FN1) and NPs (si-FN1); (C) Representative IVIS images of xenograft tissues and various organs from mice 24 h after injection with Cy5.5-labeled iRGD-NPs (si-FN1) and NPs (si-FN1), ∗ indicates p < 0.05; (D) Schematic of the in vitro cellular uptake experiment for iRGD-NPs (si-FN1); (E-F) Immunofluorescence staining (E) and FCM (F) assessing the uptake of iRGD-NPs (si-FN1) by GBC-SD/GEM and NOZ/GEM cells, Scale bars = 25 μm; (G) 3D tumor spheroid model assessing the tumor-penetration capability conferred by iRGD modification (Scale bars = 500 μm). experiments repeated three times. Each group consists of 3 nude mice.

Article Snippet: The NPs (si-FN1) were then conjugated with iRGD peptides (HY-P0122, MCE, USA) through the interaction of the Mal group in Mal–PEG–PLGA with thiol groups in the iRGD peptide for 24 h. The molar ratio of NPs (si-FN1) to iRGD used for binding was 4:1.

Techniques: In Vivo, In Vitro, Injection, Labeling, Immunofluorescence, Staining, Modification

Journal: Materials Today Bio

Article Title: Targeting FN1 to overcome gemcitabine resistance in gallbladder cancer: Mechanistic insights and an iRGD-modified PEG-PLGA nanoparticle delivery strategy

doi: 10.1016/j.mtbio.2026.102877

Figure Lengend Snippet: Impact of NPs delivering si-FN1 on drug resistance and immune cell infiltration in GBC-SD/GEM cells. Note: (A) Schematic of the experimental setup for studying the impact of NPs delivering si-FN1 on GBC GEM resistance; (B-C) RT-qPCR (B) and Western Blot (C) analysis of FN1 and PI3K pathway protein expression in GBC-SD/GEM cells treated with NPs (si-FN1) and iRGD-NPs (si-FN1); (D) CCK-8 assay assessing the viability changes in GBC-SD/GEM cells after treatment with NPs (si-FN1) and iRGD-NPs (si-FN1); (E) Clonogenic assay evaluating colony formation in various groups of GBC-SD/GEM and NOZ/GEM cells; (F) FCM analysis of apoptosis in GBC-SD/GEM cells across different groups; (G) FCM analysis of Tregs levels in CD4 + T cells after co-culture with GBC-SD/GEM cells; (H) FCM analysis of M2 and M1 macrophage levels in THP-1 cells after co-culture with GBC-SD/GEM cells; (I) RT-qPCR analysis of IL-10 or CSF-1 expression in CD4 + T or THP-1 cells co-cultured with GBC-SD/GEM cells. ∗ indicates p < 0.05 compared to the NPs (si-NC) group, # indicates p < 0.05 compared to the NPs (si-FN1) group, experiments repeated three times.

Article Snippet: The NPs (si-FN1) were then conjugated with iRGD peptides (HY-P0122, MCE, USA) through the interaction of the Mal group in Mal–PEG–PLGA with thiol groups in the iRGD peptide for 24 h. The molar ratio of NPs (si-FN1) to iRGD used for binding was 4:1.

Techniques: Quantitative RT-PCR, Western Blot, Expressing, CCK-8 Assay, Clonogenic Assay, Co-Culture Assay, Cell Culture

Journal: Materials Today Bio

Article Title: Targeting FN1 to overcome gemcitabine resistance in gallbladder cancer: Mechanistic insights and an iRGD-modified PEG-PLGA nanoparticle delivery strategy

doi: 10.1016/j.mtbio.2026.102877

Figure Lengend Snippet: Impact of NPs delivering si-FN1 on tumorigenesis and the immunosuppressive environment in GBC-SD/GEM cells. Note: (A) Schematic of the in vivo therapeutic efficacy experiment for iRGD-NPs (si-FN1); (B-C) RT-qPCR (B) and Western Blot (C) analysis of FN1 and PI3K pathway protein expression in xenograft tissues from various mouse groups; (D) Post-dissection images of xenograft tumors from different mouse groups; (E) IVIS monitoring of tumor growth in xenograft mice from weeks 1 to 5; (F) Tumor weight statistics of different mouse groups at week 5; (G-H) Immunohistochemistry and TUNEL staining assessing Ki67 protein expression and apoptosis in tumor tissues from various mouse groups (Scale bars = 50 μm); (I) FCM analysis of Tregs infiltration levels in GBC-SD/GEM cell xenograft tissues from different mouse groups; (J) FCM analysis of M2 and M1 macrophage infiltration levels in GBC-SD/GEM cell xenograft tissues from various mouse groups; (K) RT-qPCR analysis of the expression of immunosuppressive factors in GBC-SD/GEM cell xenograft tissues from different mouse groups. ∗ indicates p < 0.05 compared to the NPs (si-NC) + GEM group, # indicates p < 0.05 compared to the NPs (si-FN1) + GEM group, each group consisting of 6 mice.

Article Snippet: The NPs (si-FN1) were then conjugated with iRGD peptides (HY-P0122, MCE, USA) through the interaction of the Mal group in Mal–PEG–PLGA with thiol groups in the iRGD peptide for 24 h. The molar ratio of NPs (si-FN1) to iRGD used for binding was 4:1.

Techniques: In Vivo, Drug discovery, Quantitative RT-PCR, Western Blot, Expressing, Dissection, Immunohistochemistry, TUNEL Assay, Staining

Journal: Pharmaceutics

Article Title: Pancreatic Cancer-Targeting Cascade Nanoamplifier Enables Self-Replenishing H 2 O 2 Generation and Autophagy Disruption in Chemodynamic Therapy

doi: 10.3390/pharmaceutics17091201

Figure Lengend Snippet: Schematic illustration of the construction of H-MnO 2 /GOX&CQ-iRGD and its mechanism of action in pancreatic tumor chemodynamic therapy. The iRGD peptide mediates nanoparticle penetration through the dense stromal barrier. In the acidic TME, sequential degradation releases Mn 2+ , O 2 , GOX, and CQ. GOX catalyzes glucose oxidation to generate H 2 O 2 , which reacts with Mn 2+ via Fenton chemistry to produce hydroxyl radicals (∙OH), to enhance the chemodynamic effect and induce tumor cell death. Concurrently, oxidative damage may trigger protective autophagy in tumor cells, which is effectively suppressed by CQ through inhibition of autolysosomal degradation, thereby reducing tumor cell resistance to CDT and further amplifying the therapeutic efficacy.

Article Snippet: The bifunctional cyclic peptide iRGD was obtained from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Inhibition, Drug discovery

Journal: Pharmaceutics

Article Title: Pancreatic Cancer-Targeting Cascade Nanoamplifier Enables Self-Replenishing H 2 O 2 Generation and Autophagy Disruption in Chemodynamic Therapy

doi: 10.3390/pharmaceutics17091201

Figure Lengend Snippet: Construction and physicochemical characterization of H-MnO 2 /GOX&CQ-iRGD. ( A ) Stepwise synthetic route: silica templating → PEI-mediated MnO 2 shell formation → core removal → sequential loading of GOX and CQ → PEI and PAA surface coatings → iRGD conjugation. ( B ) FTIR spectra of intermediates: (1) H-MnO 2 , (2) H-MnO 2 /GOX&CQ, (3) H-MnO 2 /GOX&CQ@PEI, (4) H-MnO 2 /GOX&CQ@PAA, and (5) H-MnO 2 /GOX&CQ-iRGD. ( C ) Zeta potentials of samples 1–5, illustrating surface charge shifts following each modification step. ( D ) UV–Vis absorption spectra of H-MnO 2 (5 mg mL −1 ), CQ (500 μg mL −1 ), GOX (750 μg mL −1 ), iRGD (1 mg mL −1 ), and the final H-MnO 2 /GOX&CQ-iRGD, showing characteristic peaks at 329 nm (CQ) and 445 nm (GOX). ( E ) Hydrodynamic diameter distribution of H-MnO 2 /GOX&CQ-iRGD measured by DLS, centered at ~200 nm with narrow polydispersity.

Article Snippet: The bifunctional cyclic peptide iRGD was obtained from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Conjugation Assay, Modification

Journal: Pharmaceutics

Article Title: Pancreatic Cancer-Targeting Cascade Nanoamplifier Enables Self-Replenishing H 2 O 2 Generation and Autophagy Disruption in Chemodynamic Therapy

doi: 10.3390/pharmaceutics17091201

Figure Lengend Snippet: Solution-level evaluation of H-MnO 2 /GOX&CQ-iRGD in vitro. ( A ) TEM images after 12 h incubation under: pH 7.4; pH 6.5; pH 6.5 + 100 μM H 2 O 2 ; pH 6.5 + 100 μM H 2 O 2 + 5 mM GSH, illustrating pH/GSH-triggered shell collapse. ( B ) O 2 concentration over time at different concentrations of H-MnO 2 /GOX&CQ-iRGD in simulated TME solution (hypoxia, pH 6.5 + H 2 O 2 + GSH, GSH: 5 mM, H 2 O 2 : 100 μM). ( C ) Time-dependent H 2 O 2 generation in tumor-mimicking buffer (pH 6.5 + H 2 O 2 + GSH), measured by HRP–ABTS assay. ( D ) UV–Vis spectra of MB after 2 h treatment under different conditions, indicating ∙OH-mediated MB degradation. ( E ) MB degradation following 2 h incubation with increasing concentrations of H-MnO 2 /GOX and glucose, showing a dose-dependent ∙OH generation.

Article Snippet: The bifunctional cyclic peptide iRGD was obtained from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: In Vitro, Incubation, Concentration Assay, ABTS Assay

Journal: Pharmaceutics

Article Title: Pancreatic Cancer-Targeting Cascade Nanoamplifier Enables Self-Replenishing H 2 O 2 Generation and Autophagy Disruption in Chemodynamic Therapy

doi: 10.3390/pharmaceutics17091201

Figure Lengend Snippet: Cellular-level evaluation of H-MnO 2 /GOX&CQ-iRGD in PANC-1 cells. ( A ) Relative metabolic activity of PANC-1 cells after 24 h treatment with H-MnO 2 -iRGD, H-MnO 2 /GOX-iRGD, H-MnO 2 /CQ-iRGD, and H-MnO 2 /GOX&CQ-iRGD. (Concentration unit: μg/mL). ( B ) Confocal fluorescence images of Cy5-labeled H-MnO 2 /GOX&CQ-iRGD uptake at 1, 2, and 3 h (DAPI = blue nuclei; Cy5 = red) (scale bar: 20 μm). ( C ) Intracellular ROS detection by DHE staining under different treatments (λem = 610 nm). ( D ) P62 immunofluorescence for autophagy inhibition following treatment; increased P62 puncta indicate blocked autophagic flux (scale bar: 50 μm). ( E , F ) WB analysis of P62 accumulation in PANC-1 cells. ( G ) Comparative metabolism showing synergistic cytotoxicity of the dual-functional nanoplatform. Statistical significance: * p < 0.05; *** p < 0.001; **** p < 0.0001.

Article Snippet: The bifunctional cyclic peptide iRGD was obtained from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Activity Assay, Concentration Assay, Fluorescence, Labeling, Staining, Immunofluorescence, Inhibition, Functional Assay

Journal: Pharmaceutics

Article Title: Pancreatic Cancer-Targeting Cascade Nanoamplifier Enables Self-Replenishing H 2 O 2 Generation and Autophagy Disruption in Chemodynamic Therapy

doi: 10.3390/pharmaceutics17091201

Figure Lengend Snippet: In vivo targeting and therapeutic efficacy of H-MnO 2 /GOX&CQ-iRGD in a pancreatic cancer mouse model. ( A ) Fluorescence imaging and quantitative ROI analysis of Cy7-labeled H-MnO 2 /GOX&CQ-iRGD showing tumor accumulation over 24 h ( n = 3). ( B ) Representative images of tumor-bearing mice after 20 days of treatment. ( C ) Kaplan–Meier survival curves for each group. ( D , E ) Body weight ( D ) and tumor volume ( E ) changes during the 28-day treatment. Tumor volumes were analyzed by two-way ANOVA with Tukey’s post hoc test; survival was analyzed using the log-rank (Gehan–Breslow–Wilcoxon) test. Statistical significance: * p < 0.05, ** p < 0.01, *** p < 0.001. Treatment groups: (1) Control, (2) H-MnO 2 -iRGD, (3) H-MnO 2 /GOX-iRGD, (4) H-MnO 2 /CQ-iRGD, and (5) H-MnO 2 /GOX&CQ-iRGD. ( F ) H&E and TUNEL staining of tumor sections showing extensive necrosis and apoptosis in the dual-loaded group compared to limited effects in control and single-agent groups. ( G ) H&E staining of major organs showing no signs of systemic toxicity.

Article Snippet: The bifunctional cyclic peptide iRGD was obtained from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: In Vivo, Drug discovery, Fluorescence, Imaging, Labeling, Control, TUNEL Assay, Staining