Photodynamic and Sonodynamic Therapies in Atherosclerotic Disease

Atherosclerosis, driven by lipid accumulation and chronic inflammation within arterial walls, remains the principal cause of cardiovascular morbidity worldwide. Photodynamic therapy and sonodynamic therapy harness light- or ultrasound-activated sensitising agents to generate reactive oxygen species in situ, selectively inducing apoptosis, autophagy and enhanced cholesterol efflux in foam cell–rich plaques. These modalities offer precise lesion targeting with minimal collateral damage, complementing existing pharmacotherapies and interventional approaches. Advances in nanocarrier design and theranostic platforms have improved tissue penetration, photosensitiser delivery and real-time imaging of treatment efficacy. Current challenges include optimisation of activation protocols, deep-tissue access and long-term safety, yet the integration of these approaches into clinical workflows promises a new era of minimally invasive, plaque-stabilising therapies with potential to reduce the burden of ischaemic events globally.

Research from Nature Portfolio

Recent investigations have demonstrated that aminolevulinic acid–mediated sonodynamic therapy can attenuate neointimal hyperplasia following vascular injury without compromising endothelial regeneration. In preclinical models, single-session ultrasound activation elicited macrophage apoptosis via ROS-PPARγ-NF-κB signalling, reduced smooth muscle cell proliferation and improved blood flow, suggesting compatibility with stent deployment strategies. These findings underscore the potential of sonodynamic interventions to prevent restenosis while preserving vascular integrity.

Photodynamic and Sonodynamic Therapies in Atherosclerotic Disease publication trend

The graph below shows the total number of articles in photodynamic and sonodynamic therapies in atherosclerotic disease across all publications each year (not limited to Nature Index journals).

Technical terms

Photodynamic therapy (PDT): A treatment modality using light-activated photosensitisers to produce reactive oxygen species for targeted tissue ablation.

Sonodynamic therapy (SDT): A therapeutic approach employing ultrasound-activated sensitising agents to generate cytotoxic species and induce cellular apoptosis.

Photosensitiser: A compound that, upon activation by light or ultrasound, produces reactive oxygen species to effect cellular damage.

Reactive oxygen species (ROS): Highly reactive oxygen-derived molecules that mediate oxidative stress and trigger cell death or signalling pathways.

Foam cells: Lipid-engorged macrophages within atherosclerotic plaques that drive inflammation and lesion growth.

Efferocytosis: The process by which phagocytes clear apoptotic cells, facilitating inflammation resolution and tissue repair.

PPARγ-LXRα-ABCA1/ABCG1 pathway: A nuclear receptor-driven signalling cascade that promotes cholesterol efflux from macrophage foam cells.

Theranostic: An integrated strategy combining therapeutic intervention with diagnostic imaging for real-time treatment monitoring.

References

1. Photodynamic Therapy for Atherosclerosis: Past, Present, and Future. Pharmaceutics (2024).
2. Early modulation of macrophage ROS-PPARγ-NF-κB signalling by sonodynamic therapy attenuates neointimal hyperplasia in rabbits. Scientific Reports (2020).
3. Upconversion nanoparticle-mediated photodynamic therapy induces autophagy and cholesterol efflux of macrophage-derived foam cells via ROS generation. Cell Death & Disease (2017).
4. Sonodynamic therapy-induced foam cells apoptosis activates the phagocytic PPARγ-LXRα-ABCA1/ABCG1 pathway and promotes cholesterol efflux in advanced plaque. Theranostics (2018).
5. In Vitro Photodynamic Effects of the Inclusion Nanocomplexes of Glucan and Chlorin e6 on Atherogenic Foam Cells. International Journal of Molecular Sciences (2020).
6. Targeted theranostic photoactivation on atherosclerosis. Journal of Nanobiotechnology (2021).
7. Advances in imaging and treatment of atherosclerosis based on organic nanoparticles. APL Bioengineering (2022).