Nanomaterial-Based Photothermal and Photodynamic Therapies for Cardiovascular Diseases

Cardiovascular diseases (CVDs) are a global cause of morbidity and mortality and require innovative therapeutic approaches beyond conventional and surgical procedures. Photothermal (PT) and photodynamic (PD) therapies leveraging photo-activated nanomaterials are emerging least invasive strategies for the precise management of CVDs. The translation of these nanotherapies faces considerable challenges in clinical practices due to restricted light penetration, unfavorable pharmacokinetic and pharmacodynamic studies of nanoparticles (NPs), and regulatory and long-term biosafety constraints. The scope of this review is to provide a critique of the underlying engineering features, concepts, and state-of-the-art development of PT and PD therapies, including both mechanistic principles and recent advancements of CVDs, to delineate the synergistic clinical and translational challenges, and to forecast the future directions in translating applications in precision CV medicine. Four distinct light-driven nanotherapies applicable to CVDs at an advanced stage are comprehensively analyzed for their engineering, targeting strategies, biocompatibility, and optical and thermal characteristics. Existing preclinical and clinical data on the safety and efficacy of light-activated nanotherapies for CVD are reviewed. The research gaps and translational barriers towards tailoring AI-assisted therapy, hybrid phototherapy, and combinational nanomedicine strategies are explored. I. Site-specific plaque atherosclerotic ablation, thrombus removal, modulation of vascular inflammation, and photo-triggered drug release offer a targeted alternative to conventional treatments for CVDs. I. Studies reveal that response to multi-wavelength and near-infrared (NIR) light, photothermal and optical conversion efficiency, and drug caging properties of the carbon nanomaterials, gold nanorods, and upconversion NPs are improved for targeted drug activation and penetration in the deep tissues. I. Real-time monitoring, patient-specific treatment planning with dosimetry optimization are being transformed by AI and computational modeling. I. Leveraging PTT/PDT integrated with gene therapy, drug delivery, and immunomodulation generates novel multi-modality nanotherapies and enhances synergistic treatment of CVDs. V. Improvement in the inconsistent patient responses towards biocompatibility, biodegradability, controlled release, and clearance to avoid long-term toxicity, and lack of clinical standardization pose challenges, even with promising preclinical findings. Next generation phototherapies for their potential clinical impact need (i) establishing regulatory framework for validation and prototype treatment for direct large-scale clinical studies (ii) customization of integrating AI-driven precision medicine for individualized therapies (iii) enhanced biocompatibility, biodegradability, and controlled clearance of NPs (iv) increasing deep tissue penetration with the use of multi-wavelength and NIR responsive platforms. Photo-activated nanotherapies represent a transformative paradigm shift into advanced CV precision medicine by providing highly targeted, least invasive, and multifunctional treatment regimens. Efforts in engineering and multidisciplinary technological innovations, along with stringent clinical proof/validation, can make PTT and PDT effective in the treatment of CVD patients, which in turn will improve the overall patient care and survival rates over time. • Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide, necessitating innovative treatment options beyond traditional medical or surgical interventions. • Recent advancements in nanotechnology have enabled the development of sophisticated photothermal therapy (PTT) and photodynamic therapy (PDT) for non-invasive cardiovascular care. • This review examines the foundational concepts, technological advancements, engineering strategies, potential clinical applications, and translational challenges of light-activated nanotherapies in cardiovascular medicine. • Engineered nanomaterials have enhanced PTT and PDT, allowing for photothermal ablation and targeted drug delivery to treat atherosclerotic plaques, oxidative stress, and vascular remodeling. • Despite progress, challenges such as limited light penetration, nanoparticle clearance, long-term toxicity, patient variability, and regulatory hurdles persist. • Future research should focus on developing multi-wavelength and near-infrared (NIR) responsive nanoplatforms for improved light penetration, utilizing AI and computational models for personalized light dosing, and creating hybrid PTT-PDT systems for integrated cardiovascular interventions. • Ensuring long-term biocompatibility and addressing safety concerns through nanomaterial biodegradability and pharmacokinetics are critical. • Expanding animal models and conducting human trials are essential to bridge the gap between preclinical and clinical research. • In conclusion, light-activated nanotherapies have the potential to revolutionize precision medicine for CVDs, with the promise of improved patient outcomes and survival rates through the integration of theranostic nanoplatforms and AI-assisted phototherapy.