Intra-arterial drug and light delivery for photodynamic therapy using Visudyne®: implication for atherosclerotic plaque treatment
Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic a...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-09-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00400/full |
| _version_ | 1828155058344165376 |
|---|---|
| author | Manish Jain Matthieu Zellweger Aurélien Frobert Jérémy Valentin Hubert van den Bergh Georges Wagnières Stéphane Cook Marie-Noelle Giraud |
| author_facet | Manish Jain Matthieu Zellweger Aurélien Frobert Jérémy Valentin Hubert van den Bergh Georges Wagnières Stéphane Cook Marie-Noelle Giraud |
| author_sort | Manish Jain |
| collection | DOAJ |
| description | Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus this intra-arterial PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. Aim: We characterized the dose-dependent uptake and efficacy of intra-arterial PDT using Liposomal Verteporfin (Visudyne®), efficient for cancer-PDT but not tested before for PDT of atherosclerosis. Methods and Results: Visudyne® (100, 200 and 500 ng/ml) was perfused for 5-30 minutes in atherosclerotic aorta isolated from ApoE-/- mice. The fluorescence Intensity (FI) after 15 minutes of Visudyne® perfusion increased with doses of 100 (FI-5.5 ± 1.8), 200 (FI-31.9 ± 1.9) or 500 ng/ml (FI-42.9 ± 1.2). Visudyne® (500 ng/ml) uptake also increased with the administration time from 5 minutes (FI-9.8 ± 2.5) to 10 minutes (FI-23.3 ± 3.0) and 15 minutes (FI-42.9 ± 3.4) before reaching saturation at 30 minutes (FI-39.3 ± 2.4) contact. Intra-arterial PDT (Fluence: 100 and 200 J/cm2, irradiance-334 mW/cm2) applied immediately after Visudyne® perfusion (500 ng/ml for 15 minutes) using a cylindrical light diffuser coupled to a diode laser (690 nm), led to an increase of ROS (Dihydroethidium) (FI-6.9 ± 1.8, 25.3 ± 5.5, 43.4 ± 13.9) and apoptotic cells (TUNEL) (2.5 ± 1.6 %, 41.3 ± 15.3 %, 58.9 ± 6 %), mainly plaque macrophages (immunostaining) (0.3 ± 0.2 %, 37.6 ± 6.4 %, 45.3 ± 5.4 %) at light doses of 0, 100 or 200 J/cm2 respectively. Limited apoptosis was observed in the medial wall (0.5 ± 0.2 %, 8.5 ± 4.7 %, 15.3 ± 12.7 %). Finally, Visudyne®-PDT was found to be associated with reduced vessel functionality (Myogram). Conclusion: We demonstrated that sufficient accumulation of Visudyne® within plaque could be achieved in short-time and therefore validated the feasibility of local intravascular administration of photosensitizer. Intra-arterial Visudyne®-PDT preferentially affected plaque macrophages and may therefore alter the dynamic progression of plaque development. |
| first_indexed | 2024-04-11T22:47:55Z |
| format | Article |
| id | doaj.art-53c4564501e742ec9155c92f94b10854 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-11T22:47:55Z |
| publishDate | 2016-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-53c4564501e742ec9155c92f94b108542022-12-22T03:58:41ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2016-09-01710.3389/fphys.2016.00400212787Intra-arterial drug and light delivery for photodynamic therapy using Visudyne®: implication for atherosclerotic plaque treatmentManish Jain0Matthieu Zellweger1Aurélien Frobert2Jérémy Valentin3Hubert van den Bergh4Georges Wagnières5Stéphane Cook6Marie-Noelle Giraud7University of FribourgSwiss Federal Institute of Technology (EPFL)University of FribourgUniversity of FribourgSwiss Federal Institute of Technology (EPFL)Swiss Federal Institute of Technology (EPFL)University of FribourgUniversity of FribourgPhotodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus this intra-arterial PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. Aim: We characterized the dose-dependent uptake and efficacy of intra-arterial PDT using Liposomal Verteporfin (Visudyne®), efficient for cancer-PDT but not tested before for PDT of atherosclerosis. Methods and Results: Visudyne® (100, 200 and 500 ng/ml) was perfused for 5-30 minutes in atherosclerotic aorta isolated from ApoE-/- mice. The fluorescence Intensity (FI) after 15 minutes of Visudyne® perfusion increased with doses of 100 (FI-5.5 ± 1.8), 200 (FI-31.9 ± 1.9) or 500 ng/ml (FI-42.9 ± 1.2). Visudyne® (500 ng/ml) uptake also increased with the administration time from 5 minutes (FI-9.8 ± 2.5) to 10 minutes (FI-23.3 ± 3.0) and 15 minutes (FI-42.9 ± 3.4) before reaching saturation at 30 minutes (FI-39.3 ± 2.4) contact. Intra-arterial PDT (Fluence: 100 and 200 J/cm2, irradiance-334 mW/cm2) applied immediately after Visudyne® perfusion (500 ng/ml for 15 minutes) using a cylindrical light diffuser coupled to a diode laser (690 nm), led to an increase of ROS (Dihydroethidium) (FI-6.9 ± 1.8, 25.3 ± 5.5, 43.4 ± 13.9) and apoptotic cells (TUNEL) (2.5 ± 1.6 %, 41.3 ± 15.3 %, 58.9 ± 6 %), mainly plaque macrophages (immunostaining) (0.3 ± 0.2 %, 37.6 ± 6.4 %, 45.3 ± 5.4 %) at light doses of 0, 100 or 200 J/cm2 respectively. Limited apoptosis was observed in the medial wall (0.5 ± 0.2 %, 8.5 ± 4.7 %, 15.3 ± 12.7 %). Finally, Visudyne®-PDT was found to be associated with reduced vessel functionality (Myogram). Conclusion: We demonstrated that sufficient accumulation of Visudyne® within plaque could be achieved in short-time and therefore validated the feasibility of local intravascular administration of photosensitizer. Intra-arterial Visudyne®-PDT preferentially affected plaque macrophages and may therefore alter the dynamic progression of plaque development.http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00400/fullApoptosisAtherosclerosismacrophagePhotodynamic therapyVerteporfinVisudyne® |
| spellingShingle | Manish Jain Matthieu Zellweger Aurélien Frobert Jérémy Valentin Hubert van den Bergh Georges Wagnières Stéphane Cook Marie-Noelle Giraud Intra-arterial drug and light delivery for photodynamic therapy using Visudyne®: implication for atherosclerotic plaque treatment Frontiers in Physiology Apoptosis Atherosclerosis macrophage Photodynamic therapy Verteporfin Visudyne® |
| title | Intra-arterial drug and light delivery for photodynamic therapy using Visudyne®: implication for atherosclerotic plaque treatment |
| title_full | Intra-arterial drug and light delivery for photodynamic therapy using Visudyne®: implication for atherosclerotic plaque treatment |
| title_fullStr | Intra-arterial drug and light delivery for photodynamic therapy using Visudyne®: implication for atherosclerotic plaque treatment |
| title_full_unstemmed | Intra-arterial drug and light delivery for photodynamic therapy using Visudyne®: implication for atherosclerotic plaque treatment |
| title_short | Intra-arterial drug and light delivery for photodynamic therapy using Visudyne®: implication for atherosclerotic plaque treatment |
| title_sort | intra arterial drug and light delivery for photodynamic therapy using visudyne 174 implication for atherosclerotic plaque treatment |
| topic | Apoptosis Atherosclerosis macrophage Photodynamic therapy Verteporfin Visudyne® |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00400/full |
| work_keys_str_mv | AT manishjain intraarterialdrugandlightdeliveryforphotodynamictherapyusingvisudyne174implicationforatheroscleroticplaquetreatment AT matthieuzellweger intraarterialdrugandlightdeliveryforphotodynamictherapyusingvisudyne174implicationforatheroscleroticplaquetreatment AT aurelienfrobert intraarterialdrugandlightdeliveryforphotodynamictherapyusingvisudyne174implicationforatheroscleroticplaquetreatment AT jeremyvalentin intraarterialdrugandlightdeliveryforphotodynamictherapyusingvisudyne174implicationforatheroscleroticplaquetreatment AT hubertvandenbergh intraarterialdrugandlightdeliveryforphotodynamictherapyusingvisudyne174implicationforatheroscleroticplaquetreatment AT georgeswagnieres intraarterialdrugandlightdeliveryforphotodynamictherapyusingvisudyne174implicationforatheroscleroticplaquetreatment AT stephanecook intraarterialdrugandlightdeliveryforphotodynamictherapyusingvisudyne174implicationforatheroscleroticplaquetreatment AT marienoellegiraud intraarterialdrugandlightdeliveryforphotodynamictherapyusingvisudyne174implicationforatheroscleroticplaquetreatment |