Fig. 3: Co-delivery of TRPV1 antagonist and photothermal agent using polymeric micelles achieves TRPV1 blockade-synergized thermo-cytotoxicity. | Nature Communications

Fig. 3: Co-delivery of TRPV1 antagonist and photothermal agent using polymeric micelles achieves TRPV1 blockade-synergized thermo-cytotoxicity.

From: Nanoparticle-mediated TRPV1 channel blockade amplifies cancer thermo-immunotherapy via heat shock factor 1 modulation

Fig. 3: Co-delivery of TRPV1 antagonist and photothermal agent using polymeric micelles achieves TRPV1 blockade-synergized thermo-cytotoxicity.The alternative text for this image may have been generated using AI.

a Schematic illustration of tumor-targeted delivery of TRPV1 antagonist (SB705498) and photothermal agent (ICG) using IS-Micelles, followed by pH-responsive drug release and ROS-mediated cytoplasmic translocation of TRPV1 antagonist to facilitate TRPV1 blockade for synergizing thermotherapy. Dash lines indicate the failure of downstream signals transduction upon blockade of hyperthermia-activated TRPV1 channel. b Size distribution of IS-Micelles using dynamic light scattering. Inset is transmission electron microscopy (TEM) image of IS-Micelles. Scale bar, 100 nm. c Temperature elevation profiles of IS-Micelles at the concentrations of 2.0, 5.0, 10.0 and 25.0 µg mL−1 ICG under light exposure. d Release profiles of SB705498 from IS-Micelles at pH 7.4, 6.5 and 5.0 (n = 3 independent experiments). e Thermo-cytotoxicity of IS-Micelles and I-Micelles against 4T1-Luc cells under light irradiation (+) (n = 3 biological replicates). CLSM images (f) and corresponding fluorescence intensity analysis (g) of EdU (green) in 4T1-Luc tumor cells treated with I-Micelles or IS-Micelles under light irradiation or not (n = 3 independent experiments). Scale bars, 50 μm. h CLSM images of HSF1 (red) in 4T1-Luc tumor cells treated with I-Micelles or IS-Micelles in the presence or absence of light irradiation. Scale bars, 50 μm. CLSM images (i) and corresponding fluorescence intensity analysis (j) of HSP70 (red) in 4T1-Luc tumor cells treated with I-Micelles or IS-Micelles under light irradiation or not (n = 3 independent experiments). Scale bars, 100 μm. Representative flow cytometry dot plot (k) and apoptotic levels (l) in 4T1-Luc tumor cells treated with I-Micelles or IS-Micelles under light irradiation or not using Annexin V-FITC/PI staining (n = 3 biological replicates). Data are presented as mean ± SD (d, e, g, j, l). Statistical significance was determined by one-way ANOVA with Tukey’s post hoc test. The experiments for b, c, f, h, and i were repeated three times independently with similar results. Source data are provided as a Source Data file.

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