Effect of crosstalk among conspirators in tumor microenvironment on niche metastasis of gastric cancer.

In Traditional Chinese medicine, the metaphoric views of the human body are based on observations of nature guided by the theory of "Yin-Yang". The direct meanings of yin and yang are the bright and dark sides of an object, which often represent a wider range of opposite properties. When we shifted our view to gastric cancer (GC), we found that there are more distinctive Yin and Yang features in the mechanism of GC development and metastasis, which is observed in many mechanisms such as GC metastasis, immune escape, and stem cell homing. When illustrating this process from the yin-yang perspective, categorizing different cells in the tumor microenvironment enables new and different perspectives to be put forward on the mechanism and treatment of GC metastasis.

NIR -I and NIR-II irradiation tumor ablation using NbS2 nanosheets as the photothermal agent.

Photothermal therapy has been considered a powerful means of cancer therapy due to its minimal invasiveness, effectiveness, and convenience. Although promising, the therapeutic effects are greatly limited as they rely on the photothermal agent (PTA). It is urgent to develop new PTAs with high photothermal conversion performance, especially under irradiation in the long-wavelength biowindows. Herein, a dual-biowindow-responsive PTA made of NbS2-PVP nanosheets was fabricated to be used both in the first near-infrared (NIR-I) and the second near-infrared (NIR-II) biowindows. With excellent hydrophilicity and biocompatibility, the nanosheets could effectively convert the near-infrared (NIR) light into heat, showing prominent photothermal stability. The calculated photothermal conversion efficiencies reached 59.2% (under NIR-I excitation) and 69.1% (under NIR-II excitation), respectively, which are comparable to those of metallic PTAs. The NbS2-PVP nanosheets had low cytotoxicity and could trigger strong photothermal treatment and cause cancer cell death upon irradiation by NIR-I or NIR-II light in vitro. Moreover, we have also demonstrated the highly efficient tissue ablation and tumor inhibition capability of NbS2-PVP nanosheets in vivo. This work explores an effective PTA of two-dimensional nanomaterials in NIR-I and NIR-II biowindows and offers a reference for the design of new kinds of PTAs.

Photosynthetic Cyanobacteria-Hybridized Black Phosphorus Nanosheets for Enhanced Tumor Photodynamic Therapy.

Photodynamic therapy (PDT) has attracted tremendous attention due to its advantages such as high safety and effectiveness compared to traditional radiotherapy and chemotherapy. However, the intratumoral hypoxic microenvironment will inevitably compromise the PDT effect of the highly oxygen-dependent type II photosensitizers, implicating the urgent demand for continuous intratumoral oxygenation. Herein, biocompatible photosynthetic cyanobacteria have been modified with inorganic two-dimensional black phosphorus nanosheets (BPNSs) to be a novel bioreactor termed as Cyan@BPNSs. Upon 660 nm laser irradiation, the photosynthetic cyanobacteria generate oxygen continuously in situ through photosynthesis, followed by the photosensitization of BPNSs for activating oxygen into singlet oxygen (1 O2 ), resulting in a large amount of 1 O2 accumulation at the tumor site and the consequent strong tumor cell killing effect both in vitro and in vivo. This work provides an attractive strategy for efficient and biocompatible PDT, meanwhile extends the scope of microbiotic nanomedicine by hybridizing microorganisms with inorganic nanophotosensitizer.

Triggering Sequential Catalytic Fenton Reaction on 2D MXenes for Hyperthermia-Augmented Synergistic Nanocatalytic Cancer Therapy.

The unique characteristics of a tumor microenvironment (TME) enable the development of new tumor-therapeutic modalities with high efficiency, biosafety, and tumor specificity. In this work, we report on the construction of photothermal-enhanced and nanocatalyst-enabled sequential catalytic reaction for TME-specific cancer therapy. This conceptual advance is achieved by engineering the surface of two-dimensional Ti3C2 MXene with two separate catalysts, including natural glucose oxidase (GOD) as glucose catalysts and superparamagnetic iron oxide nanoparticles (IONPs) as Fenton-reaction nanocatalysts. A sequential catalytic reaction is triggered by using GOD for catalyzing the tumor-overtaken glucose to generate large amounts of hydrogen peroxide molecules. Subsequently IONPs can catalyze the transformation of pregenerated hydrogen peroxide into large amounts of highly toxic hydroxyl radicals to kill the cancer cells subsequently in TME-enabled acidity condition. The two-dimensional (2D) Ti3C2 MXene matrix efficiently converts the near-infrared light into thermal energy to synergistically enhance the catalytic efficiency of this sequential catalytic reaction and therefore achieve the high synergistic cancer-therapeutic outcome, accompanied with the high biocompatibility of the constructed composite nanocatalysts. Both in vitro cancer-cell evaluation and in vivo tumor xenograft on nude mice with complete tumor eradication demonstrate the high synergistic efficiency of photothermal-enhanced sequential nanocatalytic cancer therapy. Therefore, this work substantially broadens the biomedical applications of 2D MXenes to nanocatalytic cancer therapy by enhancing the Fenton reaction-based nanocatalytic therapy via converting the near-infrared light into thermal energy and subsequently elevating the local Fenton-reaction temperature.

Construction of Nucleus-Targeting Iridium Nanocrystals for Photonic Hyperthermia-Synergized Cancer Radiotherapy.

Prominent tumor-cell nucleus targeting of radiosensitizer substantially affects the therapeutic consequence of advanced tumor radiotherapy via lethal nucleus DNA damage. Herein, ultrasmall iridium nanocrystals (Ir NCs, <5 nm) are constructed for efficient tumor-specific photonic hyperthermia-synergized radiotherapy. To endow the NCs with qualified cell nucleus-targeting performance, polyethylene glycol (PEG)-modified Ir NCs are decorated with αv ß3 integrin-targeting cyclic arginine-glycine-aspartic (c(RGDyC)), designated as RGD, peptides and human immunodeficiency virus-1 transactivator of transcription protein(TAT), respectively, facilitating the tumor-cell-membrane (with overexpressed αv ß3 integrin) and cell-nucleus targeting. The formulated Ir-RGD-TAT (Ir-R/T) NCs are demonstrated to accumulate inside the nucleus of tumor cells and generate effective DNA lesions upon X-ray irradiation. Further in vivo evaluations verify the satisfactory carcinoma destruction performance against 4T1 tumor xenografts. Importantly, the intriguing photonic NIR adsorption of Ir-R/T NCs has enabled the hyperthermia therapeutics accompanied with photoacoustic imaging modalities, achieving clinically promising biocompatible multifunctional radiosensitized nanoplatforms for effective tumor therapeutics.

Ultrasmall Cu2-xS nanodots as photothermal-enhanced Fenton nanocatalysts for synergistic tumor therapy at NIR-II biowindow.

Reactive oxygen species (ROS)-mediated nanocatalytic therapy, as conducted by the tumor microenvironment to generate toxic hydroxyl (OH) radicals with the assistant of Fenton nanocatalysts, exhibits high tumor-therapeutic promise due to its high therapeutic selectivity and desirable therapeutic outcome. The mostly explored Fe-based Fenton nanocatalysts-enabled nanocatalytic cancer therapy substantially suffers from lowed pH condition and the corresponding therapeutic effect is still far from satisfactory for further clinic application. In this work, we report, for the first time, that copper (Cu)-based nanocatalysts have the intrinsic capability to catalyze hydrogen peroxide (H2O2) into hydroxyl radicals in a wide range pH condition with the comparable and even better performance as compared to mostly explored Fe-based nanocatalysts. Especially, ultrasmall (≤5 nm) PEGylated Cu2-xS nanodots (Cu2-xS-PEG) were fabricated to serve as the novel Fenton nanocatalysts for nanocatalytic tumor therapy. Importantly, taking the unique advantage of high near infrared (NIR) light absorbance at NIR-II biowindow (1000-1350 nm), light-activated photonic theranostic modality, i.e. photoacoustic imaging and photothermal therapy at both NIR-II biowindows was introduced, which could efficiently delineate/monitor the tumor regions and synergistically enhance Fenton-mediated therapeutic efficacy by photonic hyperthermia, respectively. Both systematic in vitro and in vivo experiments have demonstrated the high therapeutic efficacy of Cu2-xS-enabled synergistic photothermal hyperthermia-enhanced nanocatalytic therapy. This work not only provides a nanoparticle-augmented synergistic cancer-therapeutic modality, but also enriches the totally new nanocatalyst types for catalytic Fenton reaction-based nanocatalytic tumor therapy.