Figure 5. (a) Schematic illustration of the formation of PEGylated Pd
SAzyme and (b) the mechanism of ferroptosis promoted by MPTT. (c) TEM
image of Pd@ZIF-8; the inset (scale bar 5 nm) is the enlarged image of
Pd@ZIF-8, showing visible Pd NPs. (d) TEM image of Pd SAzyme. (e)
HAADF-STEM images of Pd SAzyme showing the atomically dispersed Pd atoms
highlighted by yellow circles. (f) The EDS elemental mapping of Pd
SAzyme. Western blots of (g) HSP70 and (h) GPX4 after different
treatments. Reproduced from Ref. [169] with permission. Copyright
2022 Wiley-VCH.
3.3.2. Other coordination complex
Yang et al. developed a unique nanodrug called Qu-FeIIP, where quercetin
serves not only as a HSP70 inhibitor but also as the framework for
Qu-FeIIP. This innovative nanodrug allows for MPTT, effectively
eradicating tumors without subjecting normal tissues to heat stress.
Qu-FeIIP possesses the ability to scavenge ROS due to the presence of
quercetin. Consequently, Qu-FeIIP effectively reduced intracellular ROS
levels and lowered in vivo inflammatory factors such as TNF-α, IL-6, and
IFN-γ. Simultaneously, the coordination between quercetin and Fe weakens
during ROS scavenging, leading to the disassembly of Qu-FeIIP and
efficient clearance of NPs from major organs within 168 hours post
intravenous injection. Moreover, Qu-FeIIP exhibits dual-imaging
capabilities, offering PAI and MRI for precise tumor diagnosis and
real-time monitoring of nanodrug disassembly in vivo.[173] Qu-FeIIP
combines precise diagnosis, effective MPTT, ROS elimination,
anti-inflammatory action, dynamic disassembly, and renal clearance into
a single nanodrug, holding significant promise for future clinical
cancer treatment. Yu et al. introduced a self-assembling nanoagent
termed ZCNA, which is formed by the integration of hydrophobic
Cu2-xS nanoparticles and zinc protoporphyrin (ZnPP)
using a simple volatilization-driven approach, without the need for
additional stabilizing or carrier materials. This nanoagent offers
several notable features, including a straightforward preparation
process, high loading efficiency and capacity for ZnPP, and excellent
biocompatibility. ZCNA serves as both a contrast agent for PAI and a
photothermal agent for MPTT.[174] Importantly, ZnPP released from
ZCNA during PTT effectively inhibits the expression of heme oxygenase-1
(HO-1, a critical type of HSPs), thereby depleting the antioxidant
defense systems of tumor cells. This mechanism contributes to the
significantly enhanced antitumor effect of ZCNA during MPTT. The
ingeniously designed ZCNA represented an effective theranostic platform
with PAI capabilities and synergistic antitumor effects, promoting the
clinical translation of MPTT. Yu et al. developed a novel
multifunctional nanotherapeutic agent, referred to as FeEP-NP, through a
one-pot self-assembly method. This approach relies on the coordination
between Fe II ions and (-)-epigallocatechin gallate (EGCG), with
poly(vinylpyrrolidone) acting as a stabilizer. The FeEP-NPs have been
designed to effectively generate toxic •OH via the Fenton reaction via
CDT. Interestingly, the specific binding between EGCG and Fe II ions
imparts the NPs with strong absorption and photothermal conversion
capabilities in NIR region, allowing them to achieve mild
hyperthermia-enhanced CDT when exposed to NIR laser irradiation.
Furthermore, the partially released EGCG accelerates the conversion of
Fe III to Fe II, boosting •OH generation and simultaneously reducing the
intracellular expression of HSP 90 to enhance MPTT.[175] The
combination of low-temperature PTT and CDT leads to more efficient tumor
suppression. Overall, these works introduce novel multifunctional
nanoplatform with a streamlined design, offering promising prospects for
future clinical applications.
4.Biomedical
applications of MPTT
4.1. Cancer
Cancer is a very serious disease,
especially due to the characteristics of diffusion and metastasis of
cancerous cells, so the disease can often develop to the middle and late
stages in a short time, resulting in high mortality.[11, 176, 177]
Therefore, once patients are diagnosed, they should be actively treated.
Cancer patients are mainly treated by surgery, radical surgery or
palliative surgery can be selected according to the condition. At the
same time, chemotherapeutics can be used for chemotherapy, and radiation
therapy can also be received. However, these traditional treatment
methods cannot significantly improve the quality of life of patients due
to limitations such as many contraindications and severe adverse
reactions.[178, 179] Therefore, there is an urgent need for
treatment methods with a wide range of applications and few adverse
reactions.
In recent years, precise treatment of tumor is becoming a trend in
clinical treatment of tumor.[180-182] With the continuous efforts of
researchers, MPTT, a tumor treatment based on nanomedicine, has
gradually entered people’s vision. MPTT uses PTAs that are injected into
the human body, so that they accumulate in tumor tissues, and under the
irradiation of external light sources (generally NIR light) to generate
heat energy to kill cancer cells. It has the characteristics of high
selectivity, small systemic toxic side effects, short treatment time
(about a few minutes), and obvious therapeutic effect. As a new type of
tumor treatment, MPTT has the advantages of non-invasive, less adverse
reactions and high targeting, which has great potential in the
development of tumor treatment. Sun et al. have successfully obtained
innocuous hollow mesoporous carbon spheres (HMCS) with a high PCE using
a one-pot synthesis method. Through modification with DSPE-PEG, the
resulting HMCS-PEG exhibited excellent stability in biological media,
making it well-suited for various biological applications. Remarkably,
when combined with the hydrophobic compound GA, which can downregulate
HSP90, the HMCS-PEG-GA system demonstrated a significant enhancement of
tumor therapeutic effects in vitro and in vivo under mild temperature
conditions (around 43 °C). The combination index (CI) value of
HMCS-PEG-GA was determined to be 0.72, indicating a strong synergistic
effect. Additionally, this nano-system exhibited excellent photothermal
imaging and PAI capabilities, which hold substantial potential for
accurate tumor diagnosis and MPTT applications.[183] On the other
hand, Gao et al. developed a ”smart” strategy using a
peptide-hydroxychloroquine (HCQ) conjugate,
Cypate-Phe-Phe-Lys(SAHCQ)-Tyr(H2PO3)-OH (Cyp-HCQ-Yp), which allowed for
enzyme-triggered intracellular NPs formation and HCQ release. Through
the sequential catalysis of alkaline phosphatase and carboxylesterase,
Cyp-HCQ-Yp was converted to Cypate-Phe-Phe-Lys(SA)-Tyr-OH (Cyp-Y), which
self-assembles into Cyp-NP while HCQ is released from Cyp-HCQ-Yp. This
approach achieves remarkable therapeutic effects on tumors in vivo
through dual-enzyme-controlled intracellular NPs formation and autophagy
inhibition in tumors when compared to control agents.[184] These
strategies offer promising avenues for enhancing the efficacy of MPTT
and tumor treatment. Wen et al. introduced an innovative approach
involving defect-rich glassy IrTe2(G-IrTe2) with weak Ir−Te bond strength for synergistic
SDT, CDT, and MPTT. G-IrTe2, when used as a
sonosensitizer under ultrasound (US) stimuli, demonstrates outstanding
performance in the production of ROS. Additionally,
G-IrTe2 exhibits catalase (CAT)-like activity, providing
an ample supply of oxygen to enhance the SDT effect. Theoretical
calculations validate that US stimuli can easily break the irregular
Ir−Te bonds in amorphous IrTe2, releasing free electrons
that combine with oxygen to generate1O2. Furthermore,
G-IrTe2, with peroxidase (POD)-like activity, catalyzes
endogenous H2O2 to produce more ROS for
CDT, thereby facilitating improved tumor ablation. The ROS generated
during sono-/chemodynamic processes can lead to mitochondrial
dysfunction and subsequently downregulate the expression of HSPs,
maximizing the efficacy of MPTT.[185] IrTe2 with
rich defects played a significant role in synergistic cancer therapy,
achieving outstanding antitumor efficacy. This study presented a novel
research direction for expanding the application of inorganic glassy
nanomaterials to enhance the therapeutic effects of tumors. Peng et al.
have focused on the development of a nanoagent designed to induce
heat-synergetic pro-survival autophagy to optimize the efficacy of MPTT.
Their approach involved coating a carbon layer, polyethylenimine (PEI),
and folic acid (FA) onto
NaYF4:Er,Yb,Nd@NaNdF4 (DCNPs@C@PEI@FA,
DCPF) NPs in succession. This modification allowed the nanoagent to
induce pro-survival autophagy. The resulting imaging-guided photothermal
nanoagent exhibited remarkable targeting ability and biocompatibility.
When combined with the autophagy inhibitor chloroquine, a significant
synergistic effect is observed in vitro and in vivo tumor models,
enhancing the effectiveness of DCPF-mediated MPTT.[186] This study
presented a promising strategy for improving the efficacy of
imaging-guided PTT by modulating the autophagy induced by the nanoagent.
Liu et al. have introduced an innovative strategy involving
pyroptosis-boosted MPTT with a Mn-gallate nanoformulation. This
nanoformulation was constructed through the coordination of GA and
Mn2+. Notably, it exhibited acid-activated
degradation, leading to the release of both Mn2+ and
GA. This release resulted in the upregulation of ROS, mitochondrial
dysfunction, and pyroptosis.[187] These cellular processes
contributed to ATP deprivation, achieved through both the inhibition of
ATP generation and increased ATP efflux. The reduction of ATP levels and
the accumulation of ROS provided a potent approach for inhibiting the
expression of HSPs, facilitating the MPTT. Hu et al. developed a
supramolecular drug nanocarrier designed to co-deliver NO and NIR-II
aggregation-induced emission (AIE) molecules for MPTT. Within the
intracellular reductive environment, NO is effectively released from the
nanocarriers, while DCTBT simultaneously generates ROS and hyperthermia
upon exposure to an 808 nm laser. The generated ROS can further react
with NO to produce peroxynitrite (ONOOˉ), which possessed strong
oxidization and nitration capabilities. ONOOˉ played a crucial role in
inhibiting the expression of HSPs, thereby reducing the thermoresistance
of cancer cells. This reduction in thermoresistance is essential for
achieving excellent therapeutic efficacy in DCTBT-based MPTT (Figure
6).[188] The study’s effectiveness is demonstrated through the
antitumor performance of ONOOˉ-potentiated MPTT in subcutaneous and
orthotopic hepatocellular carcinoma models. This research introduced an
innovative strategy to overcome thermoresistance for MPTT, offering new
insights into ONOOˉ-sensitized tumor therapy strategies.