Figure 7. (a) Rhythm MPTT can significantly increase immunogenicity and tumor-killing efficiency. (B) A combination of rhythm MPTT and PD-L1 blockade can unify antitumor efficiency and immune activation to obtain the optimum outcomes. (c) CLSM image of the dead cell receiving rhythm MPTT. Scale bar = 200 μm. (d) Picture of excised solid tumors of OSCC treated with MPTT. (e) Mature DCs in lymph nodes analyzed by FACS (n = 3, mean ± SD, **p < 0.01, **p < 0.01; ns, not significant). Reproduced from Ref. [201] with permission. Copyright 2023 Wiley-VCH.
4.2. Vascular diseases
Cardiovascular disease (CVD) is the leading cause of human death, accounting for 16.6 million deaths every year. Nearly a third of these deaths are due to stroke. Most strokes are caused by clots forming in blood vessels that innervate the brain.[202-204] In addition, for the elderly, due to the aging of blood vessels and the damage of blood vessel wall, they are prone to hypertension, arteriosclerosis, diabetes, and other related diseases, which are also prone to induce thrombosis. Most of the existing antithrombotic drugs have the shortcomings of easy inactivation in vivo and short circulation cycle, and the clinical efficacy is not ideal. Therefore, surgery is still the main treatment for severe thrombosis. If an efficient precision drug treatment system for thrombosis can be constructed, it will have important scientific significance for the non-invasive treatment of thrombosis. Fibrinolytic drugs are widely used in clinical practice, but the risk of fatal bleeding after thrombolysis is a major limitation of their clinical application.[205, 206] Therefore, it is of great significance to seek more accurate, safer, and more effective thrombolytic strategies to reduce the risk of thrombolytic bleeding and improve the prognosis of thrombolytic therapy. Recently, NIR light-mediated MPTT has received considerable attention. Studies have shown that some nanomaterials can convert light energy into heat energy through Landau damping effect under NIR irradiation and damage the structure of adjacent molecules. Wang et al. conducted a study aimed at addressing inflammatory macrophage (Mφ)-mediated atherosclerosis, a major cause of mortality and morbidity worldwide. They explored the use of MPTT as an effective strategy for treating inflammation in atherosclerosis. In particular, the study focused on the selection of appropriate nanomaterials, the underlying mechanisms, and the potential side effects associated with this therapy.[207] The researchers utilized semiconductor nanomaterials, specifically MoO2nanoclusters, in MPTT for the treatment of inflammatory Mφ-mediated atherosclerosis. They optimized the quantity of MoO2 and treatment duration to achieve the maximum ablation effect on Mφ while minimizing damage to endothelial cells. This optimization was achieved without the need for additional targeting or selective groups, making the approach more versatile. The MoO2-based MPTT demonstrated remarkable therapeutic efficacy in treating atherosclerosis by eliminating Mφ in animal models. Importantly, the treatment did not lead to significant side effects, highlighting its safety profile. This study introduced a novel approach to nanotechnology and pharmaceutical development by utilizing and optimizing cost-effective metal oxide nanostructures for the treatment of atherosclerosis. It also underscores the importance of further research in minimizing potential side effects associated with similar materials in medical applications. Zhang et al. conducted a study to investigate the potential of ultrasmall CuCo2S4 nanocrystals (NCs) as an effective agent for MPTT in the treatment of arterial inflammation, a critical factor in the initiation and progression of atherosclerosis (AS), a major cause of vascular diseases worldwide. The researchers synthesized CuCo2S4 NCs and utilized them as a MPTT nanoplatform for targeting arterial inflammation. They demonstrated the effective ablation of inflammatory macrophages when treated with CuCo2S4 NCs combined with irradiation using an 808 nm laser. In in vivo experiments conducted in an apolipoprotein E knockout (Apo E−/−) mouse model, local injection of CuCo2S4 NCs followed by laser irradiation resulted in significant ablation of infiltrating inflammatory macrophages. This treatment effectively reduced arterial inflammation and arterial stenosis (Figure 8).[208] This study presented a novel approach to treating AS by leveraging bimetal sulfides as potent MPTT agents. The findings offer a promising strategy for addressing arterial inflammation in the context of atherosclerosis, opening new possibilities for the treatment of this prevalent vascular disease. Dai et al. conducted a study aimed at developing a safe and effective treatment strategy for atherosclerosis by reducing intracellular lipid levels in foam cells without inducing apoptosis, which can increase the risk of plaque rupture. In their study, they employed a mild phototherapy approach using foam cell-targeted nanoprobes capable of MPTT and/or PDT. These nanoprobes were designed by loading hyaluronan and porphine onto black TiO2 NPs. The results revealed that when temperatures were kept below 45 ℃, both MPTT alone and MPTT combined with PDT significantly reduced intracellular lipid levels without inducing apoptosis or necrosis. In contrast, the use of PDT alone resulted in only a slight reduction in lipid levels but induced significant apoptosis or necrosis. The protective effect against apoptosis or necrosis observed after MPTT and MPTT + PDT was associated with the upregulation of HSP27. Furthermore, MPTT and MPTT + PDT were found to attenuate intracellular cholesterol biosynthesis, reduce excess cholesterol uptake through the SREBP2/LDLR pathway, and promote ABCA1-mediated cholesterol efflux.[209] These mechanisms collectively inhibited lipid accumulation in foam cells. The study’s findings provide valuable insights into the regulation of lipids in foam cells and suggest that the use of black TiO2 nanoprobes could enable safer and more effective phototherapy for atherosclerosis. This research offers a promising avenue for the treatment of this vascular disease. In the study by Tu et al., the aim was to develop a treatment strategy for atherosclerosis that focused on reducing intracellular lipid content in foam cells while avoiding their apoptosis, which can lead to plaque instability. To achieve this, the researchers synthesized osteopontin-coupled polydopamine (PDA-OPN) NPs and applied them to target MPTT for atherosclerosis. The study revealed that PDA-OPN were capable of specifically recognizing and being absorbed by foam cells, as observed through laser confocal microscopy. When exposed to NIR laser irradiation, the mild photothermal effect generated by PDA-OPN was effective in reducing intracellular lipid accumulation without inducing apoptosis in the foam cells. MPTT treatment led to a significant reduction in plaque area and improved plaque stability, as indicated by an increase in the expression of plaque fibrosis.[210] These findings highlight the potential of PDA-OPN mediated MPTT as a promising approach to inhibit the progression of atherosclerosis while maintaining plaque stability. These researches provide valuable insights into the development of safe and effective treatments for atherosclerosis.