Journal: Nature Communications

Article Title: Molecularly self‐fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke

doi: 10.1038/s41467-023-35895-5

Figure Lengend Snippet: The molecularly engineered nano-penetrator was self-assembled by BNN6-DiR fuel pair without the assistance of any carrier materials. After PEGylation and fibrin-homing decoration, such a self-navigated, self‐fueled, and self-propelled nano-penetrator displayed satisfactory therapeutic outcomes in artery/vein thrombosis and acute ischemic stroke animal models.

Article Snippet: As shown in Fig. , the temperature of DiR Sol, BNN6/DiR mixture solution (BD Sol), B-BD NAs, N-BD NAs, and T-BD NAs continued to rise to >50 °C within 10 min under laser irradiation, whereas the temperature of PBS (pH 7.4) did not dramatically change under the same conditions.

Techniques:

Journal: Nature Communications

Article Title: Molecularly self‐fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke

doi: 10.1038/s41467-023-35895-5

Figure Lengend Snippet: a Chemical structure of DiR, BNN6 (NO donor), and BPA (BNN6 precursor without NO production ability). b Co-assembly process of the binary NAs. c NO generation from B-BD NAs at various molar ratios of DiR and BNN6 from 10:1 to 1:10. Data are presented as mean ± SD ( n = 3, independent experiments). Source data are provided as a Source Data file. One-way ANOVA (one-sided) with Dunnett’s multiple comparisons test was used for the analysis of data and adjusted P value. d – f Particle sizes distribution profiles and TEM images of B-BD NAs, T-BD NAs, and N-BD NAs, respectively, (Scale bar = 100 nm). Experiment was repeated three times independently with similar results. g Colloidal stability of B-BD NAs, T-BD NAs, and N-BD NAs incubated in PBS (pH 7.4) within 8 h at 37 ° C. Data are presented as mean ± SD ( n = 3, independent experiments). h In vitro thrombus-targeting fluorescence intensity in artificial blood clots treated with PBS (pH 7.4), DiR Sol, B-BD NAs, N-BD NAs, and T-BD NAs, respectively. Data are presented as mean ± SD ( n = 3, independent experiments). One-way ANOVA (one-sided) with Dunnett’s multiple comparisons test was used for the analysis of data and adjusted P value. The n.s. represent no significance. i Molecular docking simulation results of BNN6 and DiR. j Particle size changes of B-BD NAs and T-BD NAs in the presence of urea (50 mM), NaCl (50 mM), and SDS (50 mM), respectively ( n = 3, independent experiments). k UV absorption spectra of DiR Sol, BNN6 Sol, B-BD NAs, and T-BD NAs. l Fluorescence spectra of DiR Sol, B-BD NAs, and T-BD NAs.

Article Snippet: As shown in Fig. , the temperature of DiR Sol, BNN6/DiR mixture solution (BD Sol), B-BD NAs, N-BD NAs, and T-BD NAs continued to rise to >50 °C within 10 min under laser irradiation, whereas the temperature of PBS (pH 7.4) did not dramatically change under the same conditions.

Techniques: Incubation, In Vitro, Fluorescence

Journal: Nature Communications

Article Title: Molecularly self‐fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke

doi: 10.1038/s41467-023-35895-5

Figure Lengend Snippet: In vitro photothermal heating a image and b curves under laser irradiation (2 W/cm 2 ). Data are presented as mean ± SD ( n = 3 independent experiments). Source data are provided as a Source Data file. c In vitro photothermal conversion efficiency of T-BD NAs. d NO release curves under laser irradiation (2 W/cm 2 ). Data are presented as mean ± SD ( n = 3, independent experiments). Source data are provided as a Source Data file. e Chemical mechanisms of NO generation from BNN6: intramolecular rearrangement and homogenous cleavage of N-NO bonds. f NO release curves of BNN6 Sol and T-BD NAs under heating (50 °C) or laser irradiation (2 W/cm 2 ). Data are presented as mean ± SD ( n = 3, independent experiments). Source data are provided as a Source Data file. g Off-on NO generation variations by the switch of laser irradiation (2 W/cm 2 ). Data are presented as mean ± SD ( n = 3, independent experiments). Source data are provided as a Source Data file. h Schematic representation of NO generation and autonomous motion features of carrier-free NAs and carrier-based NPs. i Laser-triggered NO release from T-BD NAs and PLGA-BD NAs at the same dose of DiR/BNN6 (2 W/cm 2 ). Data are presented as mean ± SD ( n = 3, independent experiments). Source data are provided as a Source Data file. One-way ANOVA (one-sided) with Dunnett’s multiple comparisons test was used for the analysis of data and adjusted P value. j The movement trajectories of T-BD NAs and PLGA-BD NAs incubated in PBS (pH 7.4) at the same dose of DiR/BNN6 under laser irradiations (0 W/cm 2 and 2 W/cm 2 , 60 s), scale bar = 1 μm. k The motion speed of T-BD NAs and PLGA-BD NPs incubated in PBS (pH 7.4) at the same dose of DiR/BNN6 under laser irradiations (2 W/cm 2 ). Data are presented as mean ± SD ( n = 3, independent experiments). Source data are provided as a Source Data file. One-way ANOVA (one-sided) with Dunnett’s multiple comparisons test was used for the analysis of data and adjusted P value. The n.s. represent no significance. Yellow lightning represents laser irradiation. L and H represent laser and heating, respectively.

Article Snippet: As shown in Fig. , the temperature of DiR Sol, BNN6/DiR mixture solution (BD Sol), B-BD NAs, N-BD NAs, and T-BD NAs continued to rise to >50 °C within 10 min under laser irradiation, whereas the temperature of PBS (pH 7.4) did not dramatically change under the same conditions.

Techniques: In Vitro, Irradiation, Incubation

Journal: Nature Communications

Article Title: Molecularly self‐fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke

doi: 10.1038/s41467-023-35895-5

Figure Lengend Snippet: a Schematic representation of photothermal/mechanical synergistic thrombolysis and clot-deep penetration. b Photos of blood clots after different treatments with/without the 808 nm NIR laser irradiation: (2 W/cm 2 , 20 min). c Fibrin and hemoglobin levels in the blood clot supernatants after different treatments with/without the 808 nm NIR laser irradiation. Data are presented as mean ± SD ( n = 3, independent experiments). Source data are provided as a Source Data file. One-way ANOVA (one-sided) with Dunnett’s multiple comparisons test was used for the analysis of data and adjusted P value. The n.s. represent no significance. d Images of blood clots before and after different treatments with 808 nm NIR laser irradiation (2 W/cm 2 , 20 min), scale bar = 2 mm. e H&E staining results of d under 808 nm NIR laser irradiation (2 W/cm 2 , 20 min), scale bar = 100 μm. f Thrombolytic rates of d under 808 nm NIR laser irradiation (2 W/cm 2 , 20 min). Data are presented as mean ± SD ( n = 3, independent experiments). Source data are provided as a Source Data file. One-way ANOVA (one-sided) with Dunnett’s multiple comparisons test was used for the analysis of data and adjusted P value. The n.s. represent no significance. g CLSM images of small red thrombi incubated with free C-6, C6/B-BD NAs, C6/N-BD NAs, or C6/T-BD NAs under 808 nm laser irradiation (2 W/cm 2 , 15 min), scale bar = 100 μm. Experiment was repeated three times independently with similar results. h Quantitative results of the depth of clot penetration. (I: PBS, II: BNN6 Sol, III: DiR Sol, IV: BD Sol, V: B-BD NAs, VI: T-BD NAs, VII: N-BD NAs). The lightning bolt represents laser irradiation.

Article Snippet: As shown in Fig. , the temperature of DiR Sol, BNN6/DiR mixture solution (BD Sol), B-BD NAs, N-BD NAs, and T-BD NAs continued to rise to >50 °C within 10 min under laser irradiation, whereas the temperature of PBS (pH 7.4) did not dramatically change under the same conditions.

Techniques: Irradiation, Staining, Incubation