Osteosarcoma-targeted Cu and Ce based oxide nanoplatform for NIR II fluorescence/magnetic resonance dual-mode imaging and ros cascade amplification along with immunotherapy.

BACKGROUND: As the lethal bone tumor, osteosarcoma often frequently occurs in children and adolescents with locally destructive and high metastasis. Distinctive kinds of nanoplatform with high therapeutical effect and precise diagnosis for osteosarcoma are urgently required. Multimodal optical imaging and programmed treatment, including synergistic photothermal-chemodynamic therapy (PTT-CDT) elicits immunogenetic cell death (ICD) is a promising strategy that possesses high bio-imaging sensitivity for accurate osteosarcoma delineating as well as appreciable therapeutic efficacy with ignorable side-effects. METHODS AND RESULTS: In this study, mesoporous Cu and Ce based oxide nanoplatform with Arg-Gly-Asp (RGD) anchoring is designed and successfully constructed. After loading with indocyanine green, this nanoplatform can be utilized for precisely targeting and efficaciously ablating against osteosarcoma via PTT boosted CDT and the closely following ICD stimulation both in vitro and in vivo. Besides, it provides off-peak fluorescence bio-imaging in the second window of near-infrared region (NIR II, 1000-1700 nm) and Magnetic resonance signal, serves as the dual-mode contrast agents for osteosarcoma tissue discrimination. CONCLUSION: Tumor targeted Cu&Ce based mesoporous nanoplatform permits efficient osteosarcoma suppression and dual-mode bio-imaging that opens new possibility for effectively diagnosing and inhibiting the clinical malignant osteosarcoma.

Physical-Chemical Coupling Coassembly Approach to Branched Magnetic Mesoporous Nanochains with Adjustable Surface Roughness.

Self-assembly processes triggered by physical or chemical driving forces have been applied to fabricate hierarchical materials with subtle nanostructures. However, various physicochemical processes often interfere with each other, and their precise control has remained a great challenge. Here, in this paper, a rational synthesis of 1D magnetite-chain and mesoporous-silica-nanorod (Fe3O4&mSiO2) branched magnetic nanochains via a physical-chemical coupling coassembly approach is reported. Magnetic-field-induced assembly of magnetite Fe3O4 nanoparticles and isotropic/anisotropic assembly of mesoporous silica are coupled to obtain the delicate 1D branched magnetic mesoporous nanochains. The nanochains with a length of 2-3 µm in length are composed of aligned Fe3O4@mSiO2 nanospheres with a diameter of 150 nm and sticked-out 300 nm long mSiO2 branches. By properly coordinating the multiple assembly processes, the density and length of mSiO2 branches can well be adjusted. Because of the unique rough surface and length in correspondence to bacteria, the designed 1D Fe3O4&mSiO2 branched magnetic nanochains show strong bacterial adhesion and pressuring ability, performing bacterial inhibition over 60% at a low concentration (15 µg mL-1). This cooperative coassembly strategy deepens the understanding of the micro-nanoscale assembly process and lays a foundation for the preparation of the assembly with adjustable surface structures and the subsequent construction of complex multilevel structures.

Conjugated Network Supporting Highly Surface-Exposed Ru Site-Based Artificial Antioxidase for Efficiently Modulating Microenvironment and Alleviating Solar Dermatitis.

Solar dermatitis, a form of acute radiation burn that affects the skin, results from overexposure to ultraviolet B (UVB) radiation in strong sunlight. Cell damage caused by the accumulation of reactive oxygen species (ROS) produced by UVB radiation plays an important role in UVB-induced inflammation in the skin. Here, for efficiently scavenging excess ROS, modulating the microenvironment, and alleviating solar dermatitis, a π-conjugated network polyphthalocyanine supporting a highly surface-exposed Ru active site-based artificial antioxidase (HSE-PPcRu) is designed and fabricated with excellent ROS-scavenging, antioxidant, and anti-inflammatory capabilities. In photodamaged human keratinocyte cells, HSE-PPcRu could modulate mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B signaling pathways, prevent DNA damage, suppress apoptosis, inhibit pro-inflammatory cytokine secretion, and alleviate cell damage. In vivo animal experiments reveal the higher antioxidant and anti-inflammatory efficacies of HSE-PPcRu by reversing the activation of p38 and c-Jun N-terminal kinase, inhibiting expression of cyclooxygenase-2, interleukin-6, interleukin-8, and tumor necrosis factor-α. This work not only provides an idea for alleviating solar dermatitis via catalytically scavenging ROS and modulating the microenvironment but also offers a strategy to design an intelligent conjugated network-based artificial antioxidase with a highly surface-exposed active site.

Ultralow Ru Single Atoms Confined in Cerium Oxide Nanoglues for Highly-Sensitive and Robust H2 O2 -Related Biocatalytic Diagnosis.

Exploring highly efficient, portable, and robust biocatalysts is a great challenge in colorimetric biosensors. To overcome the challenging states in creating single-atom biocatalysts, such as insufficient activity and stability, here, this work has engineered a unique CeO2 support as nanoglue to tightly anchor the Ru single-atom sites (CeO2 -Ru) with strong electronic coupling for achieving highly sensitive and robust H2 O2 -related biocatalytic diagnosis. The morphology and chemical/electronic structure analysis demonstrates that the Ru atoms are well-dispersed on CeO2 surface to form high-density active sites. Benefiting from the unique structure, the prepared CeO2 -Ru exhibits outstanding peroxidase (POD) like catalytic activity and selectivity to H2 O2 . Steady-state kinetic study results show that the CeO2 -Ru presents the highest Vmax and turnover number than the state-of-the-art POD-like biocatalysts. Consequently, the CeO2 -Ru discloses a high efficiency, good selectivity, and robust stability in the colorimetric detection of L-cysteine, glucose, and uric acid. Notably, the limit of detection (LOD) can reach 0.176 × 10-3 m for the L-cysteine, 0.095 × 10-3 m for the glucose, and 0.088 × 10-3 m for the uric acid via cascade reaction. This work suggests that the proposed unique CeO2 nanoglue will offer a new path to create single-atom noble metal biocatalysts and take a step closer to future biotherapeutic and biocatalytic applications.

Semiconducting Titanate Supported Ruthenium Clusterzymes for Ultrasound-Amplified Biocatalytic Tumor Nanotherapies.

The external-stimulation-induced reactive-oxygen-species (ROS) generation has attracted increasing attention in therapeutics for malignant tumors. However, engineering a nanoplatform that integrates with efficient biocatalytic ROS generation, ultrasound-amplified ROS production, and simultaneous relief of tumor hypoxia is still a great challenge. Here, we create new semiconducting titanate-supported Ru clusterzymes (RuNC/BTO) for ultrasound-amplified biocatalytic tumor nanotherapies. The morphology and chemical/electronic structure analysis prove that the biocatalyst consists of Ru nanoclusters that are tightly stabilized by Ru-O coordination on BaTiO3 . The peroxidase (POD)- and halogenperoxidase-like biocatalysis reveals that the RuNC/BTO can produce abundant •O2 - radicals. Notably, the RuNC/BTO exhibits the highest turnover number (63.29 × 10-3 s-1 ) among the state-of-the-art POD-mimics. Moreover, the catalase-like activity of the RuNC/BTO facilitates the decomposition of H2 O2 to produce O2 for relieving the hypoxia of the tumor and amplifying the ROS level via ultrasound irradiation. Finally, the systematic cellular and animal experiments have validated that the multi-modal strategy presents superior tumor cell-killing effects and suppression abilities. We believe that this work will offer an effective clusterzyme that can adapt to the tumor microenvironment-specific catalytic therapy and also provide a new pathway for engineering high-performance ROS production materials across broad therapeutics and biomedical fields.

Mesoporous tungsten titanate as matrix for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of biomolecules.

In this paper, mesoporous tungsten titanate (WTiO) with different nano-pore structures was utilized as matrix for the analysis of short peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Effect of characteristic features of mesoporous matrices on laser desorption/ionization process was investigated. Experiments showed that the ordered two-dimensional and three-dimensional mesoporous matrices were superior in performance to the non-ordered WTiO matrix. The dramatic enhancement of signal sensitivity by the ordered mesoporous matrices can be reasonably attributed to the ordered structure, which facilitated the understanding on structure-function relationship in mesoporous cavity for laser desorption process of adsorbed biomolecules. With the ordered mesoporous matrix, the short peptides are successfully detected. The presence of trace alkali metal salt effectively increased the analyte ion yields and the MALDI-TOFMS using the inorganic mesoporous matrices displayed a high salt tolerance. The developed technique also showed a satisfactory performance in peptide-mapping and amino-acid sequencing analysis.

Photoelectric performance of bacteria photosynthetic proteins entrapped on tailored mesoporous WO3-TiO2 films.

Novel three-dimensional wormlike mesoporous WO(3)-TiO(2) films with tailored pore size (approximately 7.1 nm) were applied to prepare the bio-photoelectrodes (Bio-PEs) through direct entrapping the bacteria photosynthetic reaction center (RC) proteins. These mesoporous WO(3)-TiO(2) films exhibited unique characteristics in the specific loading of RC with high activity retained. Moreover, well-matched energy levels of WO(3)-TiO(2) and RC contributed to the photoelectric performance, especially in the red to near-infrared (NIR) region, of the derived Bio-PEs. Such strategy of manipulating the Bio-PEs based on well-designed mesoporous metal oxides and RC provides an alternative system to probe the photoinduced multiple-pathway electron transfer of photosensitive chromophores, which may open a new perspective to develop versatile bio-photoelectric devices.