https://doi.org/10.1007/s00392-025-02625-4
1Charité - Universitätsmedizin Berlin Klinik für Kardiologie, Angiologie und Intensivmedizin Berlin, Deutschland; 2Center for Nano Science and Technology @PoliMi Istituto Italiano di Tecnologia Milano, Italien
Background:
Common complications in patients affected by peripheral artery disease (PAD) are represented by abnormal neo-intimal proliferation and recurrent stenosis development. Organic semiconducting nanoparticles (NPs) were developed to promote vascular regeneration upon photostimulation. This study tested the novel approach in a clinically relevant porcine model resembling stenotic and re-stenotic changes found in PAD patients.
Common complications in patients affected by peripheral artery disease (PAD) are represented by abnormal neo-intimal proliferation and recurrent stenosis development. Organic semiconducting nanoparticles (NPs) were developed to promote vascular regeneration upon photostimulation. This study tested the novel approach in a clinically relevant porcine model resembling stenotic and re-stenotic changes found in PAD patients.
Methods:
Female Landrace pigs (N=16) underwent balloon injury in the left carotid artery (LCA) to induce a clinically relevant stenosis after 10 days. Animals were randomized in two groups: i) NPs administration and implantation of an optoelectronic device (OED) for photostimulation (Treated) and ii) NPs application without OED implantation (Sham). A balloon catheter was placed in the LCA and inflated a total of 5 times for 30s with 30s break between each occlusion; after the last step, it was retracted and inflated for 30min at the minimal pressure necessary to occlude the vessel. An atraumatic vessel clamp was placed on the LCA 3cm distally from the balloon to stop blood flow. NPs were locally administered into the damaged site via the additional infusion channel of the balloon catheter. Doppler and invasive hemodynamic assessments were performed on both damage and sacrifice days.
Female Landrace pigs (N=16) underwent balloon injury in the left carotid artery (LCA) to induce a clinically relevant stenosis after 10 days. Animals were randomized in two groups: i) NPs administration and implantation of an optoelectronic device (OED) for photostimulation (Treated) and ii) NPs application without OED implantation (Sham). A balloon catheter was placed in the LCA and inflated a total of 5 times for 30s with 30s break between each occlusion; after the last step, it was retracted and inflated for 30min at the minimal pressure necessary to occlude the vessel. An atraumatic vessel clamp was placed on the LCA 3cm distally from the balloon to stop blood flow. NPs were locally administered into the damaged site via the additional infusion channel of the balloon catheter. Doppler and invasive hemodynamic assessments were performed on both damage and sacrifice days.
Results:
Doppler evaluation showed a significant increase of the post systolic velocity at sacrifice in both groups, indicating the presence of a hemodynamic relevant stenosis in Sham (118.25±41.66 vs 249.25±42.02 cm/s) but a blunted one in the Treated (108.47±31.41 vs 170.33±16.17 cm/s). An invasive estimation of instantaneous wave free ratio (iFR), blood flow (Q), and resistance (R) in the damaged vessel further demonstrated the validity of the model. At sacrifice, a significant decrease of both iFR (0.97±0.02 vs 0.86±0.08) and Q (0.76±0.11 vs 0.50±0.17 L/min), accompanied with a significant increase of R (86.60±10.64 vs 142.25±44.01 mmHg/(L/min)), occurred in Sham. Interestingly, the Treated group did not show significant changes of iFR (0.97±0.02 vs 1.00±0.03), Q (0.80±0.14 vs 0.71±0.09), and R (86.75±11.32 vs 103.50±21.30).
Doppler evaluation showed a significant increase of the post systolic velocity at sacrifice in both groups, indicating the presence of a hemodynamic relevant stenosis in Sham (118.25±41.66 vs 249.25±42.02 cm/s) but a blunted one in the Treated (108.47±31.41 vs 170.33±16.17 cm/s). An invasive estimation of instantaneous wave free ratio (iFR), blood flow (Q), and resistance (R) in the damaged vessel further demonstrated the validity of the model. At sacrifice, a significant decrease of both iFR (0.97±0.02 vs 0.86±0.08) and Q (0.76±0.11 vs 0.50±0.17 L/min), accompanied with a significant increase of R (86.60±10.64 vs 142.25±44.01 mmHg/(L/min)), occurred in Sham. Interestingly, the Treated group did not show significant changes of iFR (0.97±0.02 vs 1.00±0.03), Q (0.80±0.14 vs 0.71±0.09), and R (86.75±11.32 vs 103.50±21.30).
Conclusion: The delivery and photoactivation of organic semiconducting NPs reduced the hemodynamic severity of the stenosis over 10 days of treatment, representing a potential ground-breaking therapy for vascular regeneration in PAD patients.