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Constructing two-dimensional (2D) artificial superlattices based on single-atom and few-atom nanoclusters is of great interest for exploring exotic physics. Here we report the realization of two types of artificial germanium (Ge) superlattice self-confined by a 37×37 R25.3° superstructure of bismuth (Bi) induced electronic kagome lattice potential valleys. Scanning tunneling microscopy measurements demonstrate that Ge atoms prefer to be confined in the center of the Bi electronic kagome lattice, forming a single-atom superlattice at 120 K. In contrast, room temperature grown Ge atoms and clusters are confined in the sharing triangle corner and the center, respectively, of the kagome lattice potential valleys, forming an artificial honeycomb superlattice. First-principle calculations and Mulliken population analysis corroborate that our reported atomically thin Bi superstructure on Au(111) has a kagome surface potential valley with the center of the inner Bi hexagon and the space between the outer Bi hexagons being energetically favorable for trapping Ge atoms.
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Radionuclides theranostic are ideal "partners" for bispecific antibodies to explore the immune response of patients and synergistic treatment. A bispecific single-domain antibody-Fc fusion protein, KN046, exhibits a good treatment effect by binding to programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). An ionizing-radiation stimulus mediated by a low-dose of [131I] may be used for immunopotentiation. In this study, we established [131I]-labeled KN046 as a novel radioimmunotherapy agent to treat malignant melanoma and explored the mechanism. METHODS: After intravenous injection of [131I]-KN046, SPECT/CT imaging was applied to identify candidate targets for KN046 immunotherapy. [18F]-FDG and [68 Ga]-NOTA-GZP (granzyme B-specific PET imaging agent) micro-PET/CT imaging was used to assess the immune response in vivo after [131I]-KN046 treatment. The synergistic treatment effect of [131I]-KN046 was evaluated by exploring the [131I]-based radionuclide-induced release of tumor immunogenicity-related antigens as well as the histology and survival of tumor-bearing mice after treatment. RESULTS: The constructed [131I]-KN046 exhibited high affinity and specificity for PD-L1/CTLA-4 immune targets and had excellent in vivo intratumoral retention capability so as to achieve good antitumor efficacy. More importantly, the combination of low-dose [131I] and KN046-enhanced immunosensitivity increased the immunotherapy response rates significantly. Exposure of tumor cells to [131I]-KN046 led to upregulated expression of MHC-I and Fas surface molecules and significant increases in the degree of T-cell activation and counts of tumor-infiltrating immunocytes. CONCLUSION: Use of low-dose [131I] combined with a dual-target immunosuppressant could be exploited to identify the subset of treatment responders but also exhibited great potential for enhancing antitumor immune responses.
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Antineoplásicos , Melanoma , Animais , Camundongos , Antígeno CTLA-4 , Imunossupressores , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Antígeno B7-H1/metabolismo , Antineoplásicos/farmacologia , Radioisótopos do Iodo/uso terapêutico , Imunoterapia/métodos , ImunidadeRESUMO
Frequency upconversion optical imaging has attracted great attention due to its remarkable advantages over traditional down-conversion optical imaging. However, the development of frequency upconversion optical imaging is extremely limited. Herein, five derivatives with BODIPY structure (B1-B5) were developed to investigate its frequency upconversion luminescence (FUCL) performance by introducing electron-donating and electron-withdrawing groups. Except for the nitro group decorated derivative, the other derivatives have strong and stable FUCL around 520 nm under 635 nm light excitation. More importantly, B5 retains FUCL ability after self-assembly. When applied to FUCL imaging of cells, B5 nanoparticles can be enriched in the cytoplasm and show a good signal-to-noise ratio. Meanwhile, FUCL tumor imaging can be achieved after 1 h of injection. This study not only provides a potential agent for FUCL biomedical imaging but also develops a new strategy for designing FUCL agents that exhibit excellent performance.
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Nanopartículas , Neoplasias , Humanos , Luminescência , Nanopartículas/químicaRESUMO
BACKGROUND: Endogenous hydrogen sulfide (H2S)-responsive theranostic agents have attracted extensive attention due to their specificity for colon cancer. However, the development of such agents with high enrichment in tumors and excellent photothermal performance remains challenging. RESULTS: We prepared hyaluronic acid (HA)-coated Bi-doped cuprous oxide (Bi:Cu2O@HA) via a one-pot method. The HA specifically targets colon cancer tumor cells to improve the enrichment of Bi:Cu2O@HA at tumor sites, while the doped Bi both enhances the photothermal performance of the H2S-triggered Cu2O and serves as an agent for tumor imaging. The results in this work demonstrated that the Bi:Cu2O@HA nanoparticles exhibit good biocompatibility, target colon cancer tumor cells, facilitate computed tomography imaging, and enhanced H2S-responsive photothermal therapy performance, resulting in an excellent therapeutic effect in colon cancer. CONCLUSIONS: The novel Bi:Cu2O@HA nanoparticles exhibit excellent tumor targeting and photothermal therapeutic effects, which provide new strategies and insights for colon cancer therapy.
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Neoplasias do Colo , Nanopartículas , Linhagem Celular Tumoral , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/tratamento farmacológico , Humanos , Ácido Hialurônico , FototerapiaRESUMO
Targeted T1-T2 MRI contrast agents, which can eliminate the difficulty of image matching across multiple imaging instruments and permit specific localization of lesions, are promising candidates for more accurate diagnosis of tumors. In this study, ultrasmall Fe@Fe3O4 nanoparticles were designed and synthesized as T1-T2 dual-mode MRI contrast agents for accurate tumor imaging. First, to investigate the influence of nanoparticle size, Fe@Fe3O4 nanoparticles with diameters of 4, 8, and 12 nm were prepared, among which the 8 nm 3-(3,4-dihydroxyphenyl)propionic acid (DHCA)-modified nanoparticles exhibited the optimal T1-T2 dual-mode MRI performance. Next, to develop a tumor-targeted contrast agent, the DHCA-Fe@Fe3O4 nanoparticles were conjugated with the F56 peptide, which targets the vascular endothelial growth factor receptor, and the resulting F56-DHCA-Fe@Fe3O4 nanoparticles were found to exhibit good T1-T2 dual-mode imaging and tumor-targeting performance both in vitro and in vivo, indicating the nanoparticles represent a new research tool for accurate tumor diagnosis.
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Meios de Contraste/química , Diagnóstico por Imagem , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/química , Neoplasias/diagnóstico por imagem , Tamanho da Partícula , Resinas Acrílicas/química , Ácidos Cafeicos/química , Células HCT116 , Células Endoteliais da Veia Umbilical Humana , Humanos , Nanopartículas de Magnetita/ultraestrutura , Polietilenoglicóis/química , SolubilidadeRESUMO
The synthesis of hollow opening polyhedral cages has always been an attractive but challenging goal, especially with regard to inorganic polyhedral cages. Herein, we present a novel, 240-nuclearity giant polymolybdate cage prepared via hydrothermal synthesis. This cage is composed of 20 tripod-shaped [Mo6O22(SO3)]n-/[Mo6O21(SO4)]n- building blocks with three connected vertices and 30 cubane-type [Mo4O16]n- edge building blocks, featuring a rare, nearly regular pentagonal dodecahedron with a large inner cavity (diameter up to 1.8 nm) and 12 opening pentagonal windows. This is the highest nuclearity hollow opening dodecahedral cage reported to date. Importantly, this cage exhibits good stability in solution, as revealed by scanning transmission electron microscopy (STEM), TEM, UV-vis, and Raman spectra. In addition, the bulk sample of this compound exhibits an ultrahigh proton conductivity of 1.03 × 10-1 S cm-1 at 80 °C and 98% relative humidity, which is the highest among polyoxometalate-based crystalline proton conductors.
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Techniques for the qualitative and quantitative detection of H2S in vivo have attracted considerable attention due to the key role of H2S in various physiological and pathological processes. However, in vivo detection strategies for H2S are mainly based on fluorescence imaging, which is limited by its poor tissue penetration. Moreover, the limitations of single-mode probes are amplified in complex physiological environments. Herein, a core-shell Fe3O4@Cu2O nanoparticle was constructed as a magnetic-photoacoustic dual-mode probe for H2S detection in vitro and in vivo based on the in situ response of Cu2O to endogenous H2S in colon tumors. This probe is expected to greatly improve the accuracy of H2S detection in vivo because it employs two detection methods with complementary advantages. The new probe was experimentally applied to the in vivo and in vitro visualization of H2S in mice with colorectal cancer, validating the in situ reaction-activated dual-detection method. This work establishes a simple and efficient dual-mode imaging method based on a novel trigger mechanism. The findings provide a new strategy for colon cancer detection based on the in situ reactions at tumor sites.
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Neoplasias Colorretais/diagnóstico por imagem , Sulfeto de Hidrogênio/análise , Técnicas Fotoacústicas , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Compostos Férricos/química , Compostos Férricos/farmacologia , Células HCT116 , Humanos , Fenômenos Magnéticos , Imageamento por Ressonância Magnética , Camundongos , Camundongos Nus , Nanopartículas/química , Neoplasias Experimentais/diagnóstico por imagem , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Dual-modality contrast agents for T1-weighted magnetic resonance imaging (MRI) and photoacoustic imaging have attracted substantial attention as they combine the advantages of unlimited penetration depth and high sensitivity. However, most of the reported agents are Gd-based materials that exhibit nephrotoxicity, and few studies have focused on Fe-based materials owing to their lower relaxivity. This work describes the development of an ellagic acid (EA)-Fe nanoscale coordination polymer with high longitudinal relaxivity and strong near-infrared absorption for dual-modality T1-weighted MRI and photoacoustic imaging. The longitudinal relaxivity (r1) of the prepared EA-Fe@BSA nanoparticles was 2.54 mM-1â¯s-1, an increase of 185% compared with previously reported gallic acid-Fe nanoparticles. Furthermore, in vitro and in vivo experiments demonstrate that the EA-Fe@BSA NPs are an excellent T1-weighted MRI and photoacoustic dual-modality contrast agent with the advantages of convenient synthesis and low toxicity, exhibiting great potential for clinical use in tumor imaging.
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Meios de Contraste/química , Ácido Elágico/química , Compostos Férricos/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Polímeros/química , Técnicas FotoacústicasRESUMO
Smart theranostics agents triggered by endogenous H2 S with combined activated photoacoustic imaging and photothermal therapy can improve the diagnosis and treatment of colon cancer. However, the low theranostic performance of the current smart theranostics agents after the triggering step has limited their further application. In this work, the theranostic performance of endogenous H2 S-triggered Au@Cu2 O for the diagnosis and treatment of colon cancer, which is generated from the localized surface plasmon resonance coupling effect between a noble metal (Au) and a semiconductor (Cu2 O), is investigated. Compared with Cu2 O, the prepared H2 S-triggered Au@Cu2 O shows a significantly stronger absorption at the near-infrared region, such as a ≈2.1 times change at 808 nm, giving a photothermal conversion efficiency increase of ≈1.2 times. More importantly, Au@Cu2 O still exhibits good photoacoustic imaging contrast and photothermal properties for treatment of colon cancer in vivo even at very low injection doses. This work not only investigates an endogenous H2 S-triggered Au@Cu2 O theranostic agent with enhanced theranostic performance for colon cancer but also provides a novel strategy for designing high-performance theranostic agents.
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Cobre/química , Ouro/química , Sulfeto de Hidrogênio/química , Hipertermia Induzida , Técnicas Fotoacústicas , Fototerapia , Animais , Materiais Biocompatíveis/química , Morte Celular , Células HCT116 , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Camundongos Endogâmicos BALB C , Camundongos Nus , Sulfetos/química , Ressonância de Plasmônio de SuperfícieRESUMO
Tumor-microenvironment-responsive theranostics have great potential for precision diagnosis and effective treatment of cancer. Polyaniline (PANI) is the first reported pH-responsive organic photothermal agent and is widely used as a theranostic agent. However, tumor pH-responsive PANI-based theranostic agents are not explored, mainly because the conversion from the emeraldine base (EB) to emeraldine salt (ES) state of PANI requires pH < 4, which is lower than tumor acidic microenvironment. Herein, a tumor pH-responsive PANI-based theranostic agent is designed and prepared for amplified photoacoustic imaging guided augmented photothermal therapy (PTT), through intermolecular acid-base reactions between carboxyl groups of bovine serum albumin (BSA) and imine moieties of PANI. The albumin/PANI assemblies (BSA-PANI) can convert from the EB to ES state at pH < 7, accompanied by the absorbance redshift from visible to near-infrared region. Both in vitro and in vivo results demonstrate that tumor acidic microenvironment can trigger both the photoacoustic imaging (PAI) signal amplification and the PTT efficacy enhancement of BSA-PANI assemblies. This work not only highlights that BSA-PANI assemblies overcome the limitation of low-pH protonation, but also provides a facile assembly strategy for a tumor pH-responsive PANI-based nanoplatform for cancer theranostics.
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Compostos de Anilina/química , Hipertermia Induzida , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Técnicas Fotoacústicas , Fototerapia , Soroalbumina Bovina/química , Compostos de Anilina/síntese química , Animais , Materiais Biocompatíveis/química , Bovinos , Feminino , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos BALB C , Soroalbumina Bovina/ultraestruturaRESUMO
Fundamental understanding of the bonding motifs that elaborately mediate the formation of supramolecular nanostructures is essential for the rational design of stable artificial organic architectures. Herein, the structural transformation of the adsorption complex of 2, 7-dibromopyrene (Br2 Py) on the Au(111) surface has been investigated by scanning tunnelling microscopy combined with X-ray photoemission spectroscopy and density function theory calculations. In the initial stage of self-assembly, well ordered patterns are formed in the manner of extended supramolecular structures balanced by intermolecular halogen bonding motifs, whilst the Au(111) reconstruction is still fairly visible. Subsequent thermal annealing promotes the dehalogenation and on-surface Ullmann coupling, and polymerized oligomers are consequently constructed. Interestingly, such polymerized chains are still stably mediated by the halogen bonding motif via dissociated Br atoms which are revealed to be absorbed on the bridge site of Au(111), while the number of halogen bonds increases significantly from self-assembly to Ullmann coupling polymerization, indicating that the halogen bonding motif contributes significantly to the extended one-dimensional polymers.
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Expression of a high concentration of H2 S is closely related to the formation of colon cancer tumors. However, only a few H2 S-triggered theranostics agents for colon cancer have been reported to date. Now, a turn-on theranostics agent was developed by utilizing the inâ situ reaction of Cu2 O and endogenous H2 S at colon tumor sites. Based on inâ vitro and inâ vivo experiments, excellent photoacoustic imaging and photothermal therapy were both confirmed by this inâ situ reaction-activated colon cancer theranostics method. This work established a simple and efficient strategy for both diagnosis and treatment of colon cancer with a novel trigger mechanism, which provides a new route for colon cancer theranostics based on the inâ situ reactions at the tumor sites.
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Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Cobre/farmacologia , Sulfeto de Hidrogênio/farmacologia , Sulfetos/farmacologia , Nanomedicina Teranóstica , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/diagnóstico por imagem , Cobre/química , Células HCT116 , Humanos , Sulfeto de Hidrogênio/química , Camundongos , Nanopartículas/química , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Tamanho da Partícula , Técnicas Fotoacústicas , Fotoquimioterapia , Sulfetos/químicaRESUMO
Water-soluble polymer nanoparticles NP-1 and NP-2 were prepared by using a three-component self-assembly of an iridium complex, poly(4-vinyl pyridine-b-ethylene oxide) (P4VP-b-PEO), and methane sulfonic acid (MSA). Due to the unique metal-ligand charge-transfer transition property and the heavy-atom effect of the iridium atom, NP-1 and NP-2 showed bright phosphorescence and generated the singlet oxygen (1 O2 ) species effectively under visible-light irradiation (λ>400â nm) with a power density of 300â mW cm-2 . NP-2, an example of the polymer nanoparticles, showed minimal cytotoxic activity in the dark. Laser confocal fluorescence and flow-cytometry microscopy experiments demonstrated that NP-2 could be taken up by a model cancer-cell line of 4T1 cells, which could be used as a phosphorescent probe for cell imaging by preferentially staining the cytoplasm. After 6â hours of incubation with NP-2 (100â µg mL-1 ), the cell viability of 4T1 cells decreased to approximately 10 % upon visible-light irradiation (λ>400â nm, 300â mW cm-2 ) only for 10â minutes as a result of the generation of the 1 O2 species, thus indicating a proof of concept for effective photodynamic therapy for cancer cells.
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Magnetic Fe3 O4 crystals are produced in situ on preformed polypyrrole (PPY) nanoparticles by rationally converting the residual Fe species in the synthetic system. The obtained PPY@Fe(3)O(4)composite nanoparticles exhibit good photostability and biocompatibility, and they can be used as multifunctional probes for MRI, thermal imaging, and photothermal ablation of cancer cells.
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Compostos Férricos/química , Hipertermia Induzida/métodos , Imagem Multimodal , Nanopartículas/química , Neoplasias/terapia , Fototerapia/métodos , Polímeros/química , Pirróis/química , Animais , Células HeLa , Humanos , Imageamento por Ressonância Magnética , Camundongos , Camundongos Nus , Nanopartículas/ultraestrutura , Espectrofotometria Ultravioleta , TemperaturaRESUMO
Copper sulfide based phototherapy, including photothermal therapy and photodynamic therapy, is an emerging minimally invasive treatment of tumor, which the light was converted to heat or reactive oxygen to kill the tumor cells. Compared with conventional chemotherapy and radiation therapy, Cu2-x S based phototherapy is more efficient and has fewer side effects. However, considering the dose-dependent toxicity of Cu2-x S, the performance of Cu2-x S based phototherapy still cannot meet the requirement of the clinical application to now. To overcome this limitation, engineering of Cu2-x S to improve the phototherapy performance by increasing light absorption has attracted extensive attention. For better guidance of Cu2-x S engineering, we outline the currently engineering method being explored, including (1) structural engineering, (2) compositional engineering, (3) functional engineering, and (4) performance engineering. Also, the relationship between the engineering method and phototherapy performance was discussed in this review. In addition, the further development of Cu2-x S based phototherapy is prospected, including smart materials based phototherapy, phototherapy induced immune microenvironment modulation et al. This review will provide new ideas and opportunities for engineering of Cu2-x S with better phototherapy performance. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Cobre/química , Cobre/farmacologia , Fototerapia/métodos , Sulfetos/química , Sulfetos/farmacologia , Neoplasias/terapia , Nanopartículas/química , Microambiente TumoralRESUMO
Osteoarthritis treatment remains a significant clinical challenge. Quercetin, a natural flavonoid with anti-inflammatory and antiapoptotic properties, might be utilized to treat OA. However, poor water solubility and short joint retention duration limit its bioavailability and translation to clinical applications. A one-step self-assembly method was utilized to fabricate quercetin-loaded zeolitic imidazolate framework-8 (Qu@ZIF-8) nanoparticles using zinc ions, 2-methylimidazole, and quercetin. In vitro tests showed that Qu@ZIF-8 nanoparticles released pH-responsive agents into chondrocytes, effectively protecting them from interleukin (IL)-induced inflammation and apoptosis, thereby promoting cartilage anabolic activities. These underlying mechanisms revealed a remarkable increase of autophagy in IL-ß-treated chondrocytes, followed by the inhibition of the Pi3k/Akt signaling pathway, which contributed to the protective effect of Qu @ZIF-8. By the establishment of medial meniscus instability (DMM) in OA mice, Qu@ZIF-8 substantially improved cartilage structural integrity and chondrocyte status, as well as attenuated OA progression. Importantly, Qu@ZIF-8 outperformed quercetin alone in the treatment of OA due to its control release. The combined research findings indicate that Qu@ZIF-8 shields chondrocytes from inflammation and apoptosis by activating autophagy and repressing the Pi3k/Akt pathway. This investigation may provide new insights for clinically extending the therapy of OA.
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Autofagia , Condrócitos , Nanopartículas , Osteoartrite , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Quercetina , Transdução de Sinais , Animais , Quercetina/química , Quercetina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos , Autofagia/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Osteoartrite/metabolismo , Nanopartículas/química , Transdução de Sinais/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Zeolitas/química , Zeolitas/farmacologia , Imidazóis/química , Imidazóis/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Apoptose/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BLRESUMO
Pancreatic cancer, a prevalent malignancy of the digestive system, has a poor 5-year survival rate of around 10%. Although numerous minimally invasive alternative treatments, including photothermal therapy and photodynamic therapy, have shown effectiveness compared with traditional surgical procedures, radiotherapy, and chemotherapy. However, the application of these alternative treatments is constrained by their depth of penetration, making it challenging to treat pancreatic cancer situated deep within the tissue. Sonodynamic therapy (SDT) has emerged as a promising minimally invasive therapy method that is particularly potent against deep-seated tumors such as pancreatic cancer. However, the unique characteristics of pancreatic cancer, including a dense surrounding matrix, high reductivity, and a hypoxic tumor microenvironment, impede the efficient application of SDT. Thus, to guide the evolution of SDT for pancreatic cancer therapy, this review addresses these challenges, examines current strategies for effective SDT enhancement for pancreatic cancer, and investigates potential future advances to boost clinical applicability. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
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Neoplasias , Neoplasias Pancreáticas , Terapia por Ultrassom , Humanos , Neoplasias/terapia , Neoplasias Pancreáticas/terapia , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio , Microambiente TumoralRESUMO
Transarterial chemoembolization (TACE) is widely recognized as a non-surgical treatment approach for advanced liver cancer, combining chemotherapy with the blockage of blood vessels supplying the tumor. To enhance the efficacy of TACE and address chemotherapy resistance, there is growing interest in the development of multifunctional embolic microspheres. In this study, multifunctional PVA microspheres, which encapsulate MIT as a chemotherapeutic drug, PPY as a photothermal agent, and Fe3O4 as a chemodynamic therapy agent, were prepared successfully. The results demonstrated that the developed multifunctional PVA microspheres not only exhibit favorable drug release, photothermal therapy, and chemodynamic therapy performance, but also show a promising synergistic therapeutic effect both in vitro and in vivo. Consequently, the engineered multifunctional PVA microspheres hold tremendous promise for enhancing TACE effectiveness and have the potential to overcome limitations associated with traditional liver cancer treatments.
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Quimioembolização Terapêutica , Neoplasias Hepáticas , Microesferas , Terapia Fototérmica , Álcool de Polivinil , Álcool de Polivinil/química , Quimioembolização Terapêutica/métodos , Humanos , Animais , Camundongos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologia , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Camundongos NusRESUMO
Topological semimetals have emerged as quantum materials including Dirac, Weyl, and nodal line semimetals, and so on. Dirac nodal line (DNL) semimetals possess topologically nontrivial bands crossing along a line or a loop and are considered precursor states for other types of semimetals. Here, we combine scanning tunneling microscopy/spectroscopy (STM/S) measurements and density functional theory (DFT) calculations to investigate a twist angle tuning of electronic structure in two-dimensional DNL semimetal Au2Ge. Theoretical calculations show that two bands of Au2Ge touch each other in Γ-M and Γ-K paths, forming a DNL. A significant transition of electronic structure occurs by tuning the twist angle from 30° to 24° between monolayer Au2Ge and Au(111), as confirmed by STS measurements and DFT calculations. The disappearing of DNL state is a direct consequence of symmetry breaking.
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Intercellular communication between tumor cells and immune cells regulates tumor progression including positive communication with immune activation and negative communication with immune escape. An increasing number of methods are employed to suppress the dominant negative communication in tumors such as PD-L1/PD-1. However, how to effectively improve positive communication is still a challenge. In this study, a nuclear-targeted photodynamic nanostrategy is developed to establish positive spatiotemporal communication, further activating dual antitumor immunity, namely innate and adaptative immunity. The mSiO2 -Ion@Ce6-NLS nanoparticles (NPs) are designed, whose surface is modified by ionic liquid silicon (Ion) and nuclear localization signal peptide (NLS: PKKKRKV), and their pores are loaded with the photosensitizer hydrogen chloride e6 (Ce6). Ion-modified NPs enhance intratumoral enrichment, and NLS-modified NPs exhibit nuclear-targeted characteristics to achieve nuclear-targeted photodynamic therapy (nPDT). mSiO2 -Ion@Ce6-NLS with nPDT facilitate the release of damaged double-stranded DNA from tumor cells to activate macrophages via stimulator of interferon gene signaling and induce the immunogenic cell death of tumor cells to activate dendritic cells via "eat me" signals, ultimately leading to the recruitment of CD8+ T-cells. This therapy effectively strengthens positive communication to reshape the dual antitumor immune microenvironment, further inducing long-term immune memory, and eventually inhibiting tumor growth and recurrence.