Traditional radiotherapy can induce injury to the normal tissue around the tumor, so the development of novel radiosensitizer with high selectivity and controllability that can lead to more effective and reliable radiotherapy is highly desirable. Herein, a new smart radiosensitizer based on Cu 2 (OH)PO 4 nanocrystals that can simultaneously respond to endogenous stimulus (H 2 O 2 ) and exogenous stimulus (X-ray) is reported. First, Cu 2 (OH)PO 4 nanocrystals can generate Cu I sites under X-ray irradiation through X-ray-induced photoelectron transfer process. Then, X-ray-triggered Cu I sites serve as a catalyst for efficiently decomposing overexpressed H 2 O 2 in the tumor microenvironment into highly toxic hydroxyl radical through the Fenton-like reaction, finally inducing apoptosis and necrosis of cancer cells. Meanwhile, this nonspontaneous Fenton-like reaction is greatly limited within normal tissues because of its oxygen-rich condition and insufficient H 2 O 2 relative to tumor tissues. Thus, this strategy can ensure that the process of radiosentization can only be executed within hypoxic tumors but not in normal cells, resulting in the minimum damages to surrounding healthy tissues. As a result, the X-raytriggered Fenton-like reaction via introducing nontoxic Cu 2 (OH)PO 4 nanocrystals under the dual stimuli provides a more controllable and reliable activation approach to simultaneously enhance the radiotherapeutic efficacy and reduce side effects.
Radiotherapy (RT) in practical use often suffers from offtarget side effects and ineffectiveness against hypoxic tumor microenvironment (TME) as well as remote metastases. With regard to these problems, herein, we provide semiconductor heterojunction structured WO 2.9 -WSe 2 -PEG nanoparticles to realize a synergistic RT/photothermal therapy (PTT)/checkpoint blockade immunotherapy (CBT) for enhanced antitumor and antimetastatic effect. Based on the heterojunction structured nanoparticle with high Z element, the nanosystem could realize non-oxygen-dependent reactive oxygen species generation by catalyzing highly expressed H 2 O 2 in TME upon X-ray irradiation, which could further induce immunogenic cell death. Meanwhile, this nanosystem could also induce hyperthermia upon near-infrared irradiation to enhance RT outcome. With the addition of anti-PD-L1 antibody-based CBT, our results give potent evidence that local RT/PTT upon mild temperature and low radiation dose could efficiently ablate local tumors and inhibit tumor metastasis as well as prevent tumor rechallenge. Our study provides not only one kind of radiosensitizer based on semiconductor nanoparticles but also a versatile nanoplatform for simultaneous triple-combined therapy (RT/PTT/CBT) for treating both local and metastasis tumors.
Development of an efficient nanoradiosensitization system that enhances the radiation doses in cancer cells to sensitize radiotherapy (RT) while sparing normal tissues is highly desirable. Here, we construct a tumor microenvironment (TME)-responsive disassembled small-on-large molybdenum disulfide/hafnium dioxide (MoS 2 /HfO 2 ) dextran (M/H-D) nanoradiosensitizer. The M/H-D can degrade and release the HfO 2 nanoparticles (NPs) in TME to enhance tumor penetration of the HfO 2 NPs upon near-infrared (NIR) exposure, which can solve the bottleneck of insufficient internalization of the HfO 2 NPs. Simultaneously, the NIR photothermal therapy increased peroxidase-like catalytic efficiency of the M/H-D nanoradiosensitizer in TME, which selectively catalyzed intratumorally overexpressed H 2 O 2 into highly oxidized hydroxyl radicals (•OH). The heat induced by PTT also relieved the intratumoral hypoxia to sensitize RT. Consequently, this TME-responsive precise nanoradiosensitization achieved improved irradiation effectiveness, potent oxygenation in tumor, and efficient suppression to tumor, which can be real-time monitored by computed tomography and photoacoustic imaging.
Integrating
multifunctional nanostructures capable of radiotherapy
and photothermal ablation is an emerging alternative in killing cancer
cells. In this work, we report a novel plasmonic heterostructure formed
by decorating AuPt nanoparticles (NPs) onto the surfaces of CuS nanosheets
(AuPt@CuS NSs) as a highly effective nanotheranostic toward dual-modal
photoacoustic/computed tomography imaging and enhanced synergistic
radiophotothermal therapy. These heterostructures can confer higher
photothermal conversion efficiency via the local electromagnetic enhancement
as well as a greater radiation dose deposition in the form of glutathione
depletion and reactive oxygen species generation. As a result, the
depth of tissue penetration is improved, and hypoxia of the tumor
microenvironment is alleviated. With synergistic enhancement in the
efficacy of photothermal ablation and radiotherapy, the tumor can
be eliminated without later recurrence. It is believed that these
multifunctional heterostructures will play a vital role in future
oncotherapy with the enhanced synergistic effects of radiotherapy
and photothermal ablation under the guided imaging of a potential
dual-modality system.
In this review, we mainly summarize the latest advances in the utilization of 2D TMDCs for PTT combination cancer therapy and imaging-guided cancer combination therapy, as well as their toxicity bothin vitroandin vivo.
Radiosensitizers are agents capable
of amplifying injury to tumor
tissues by enhancing DNA damage and fortifying production of radical
oxygen species (ROS). The use of such radiosensitizers in the clinic,
however, remains limited by an insufficient ability to differentiate
between cancer and normal cells and by the presence of a reversible
glutathione system that can diminish the amount of ROS generated.
Here, to address these limitations, we design an H2O2-responsive prodrug which can be premixed with lauric acid
(melting point ∼43 °C) and loaded around the surface of
silica-coated bismuth nanoparticles (BSNPs) for cancer-specific photoradiotherapy.
Particularly, silica coating confers BSNPs with improved chemical
stability against both near-infrared light and X-rays. Upon photothermal
heating, lauric acid is melted to trigger prodrug release, followed
by its transformation into p-quinone methide via
H2O2 stimulation to irreversibly alkylate glutathione.
Concurrently, this heat boosts tumor oxygenation and helps relieve
the hypoxic microenvironment. Following sequential irradiation by
X-rays, BSNPs generate plentiful ROS, which act in combination with
these events to synergistically induce cell death via DNA breakage
and mitochondria-mediated apoptosis pathways, ultimately enabling
effective inhibition of tumor growth in vivo with
high tumor specificity and reduced side effects. Collectively, this
work presents a promising approach for the improvement of other ROS-responsive
proalkylating agents, while simultaneously highlighting a robust nanosystem
for combining these prodrugs with photoradiosensitizers to realize
precision photoradiotherapy.
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