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.