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Bone metastasis along with osteolysis is a common complication of advanced breast cancer, which directly destroys bone function and becomes one of the major causes of cancer-related mortality. It is crucial to develop a new strategy to achieve effective cancer therapy and inhibition of osteolytic bone metastasis. Metal ruthenium (Ru) complexes exhibit therapeutic potential in cancer chemotherapy. However, the clinical applications of Ru complexes were limited by poor bioavailability, lacking targeting, nonspecific distribution. Therefore, in this study, engineering of cell membrane biomimetic modification was used to construct a highly biocompatible nanoplatform with carrying Ru metal complex of RuPOP and Se nanoparticles (SeNPs). Strikingly, the obtained RPSR nanoparticles can efficiently inhibit the proliferation, invasion and migration of breast cancer cells (MDA-MB-231 cells) in vitro. More importantly, RPSR nanoparticles can induce cycle arrest, apoptosis by generating excessive intracellular (reactive oxygen species, ROS) to disrupt the normal redox balance and induce DNA damage in tumor cells. Furthermore, RPSR nanoparticles can also reshape bone microenvironment by regulating selenoproteins to inhibit osteoclasts and avoid osteolytic bone metastasis induced by tumor development. Taken together, this study not only provides an effective cell membrane biomimetic strategy to enhance the shortcomings of metal complexes, but also demonstrates potential clinical significance for the combined treatment of anti-cancer and bone metastasis inhibition. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases, exacerbating lung cancer progression. The presence of CTCs is also the main reason for the failure of nanomedicine-based lung cancer treatments. Therefore, magnetic MoSe2 nanosheets loaded with programmed death-ligand 1 (PD-L1), named PD-L1-MFP NS, were employed here to precisely capture lung cancer CTCs in the blood circulation through the tumor-targeting effect of PD-L1 killing CTCs with highly effective photothermal therapy (PTT). In addition, by increasing the expression of cytomegalovirus UL16-binding protein (ULBP) ligands on tumor cells, the PD-L1-MFP NS further activated natural killer (NK) cells and triggered NK cell-induced cancer immunotherapy, thereby enhancing the overall tumor-killing effect. In summary, this material designed to capture CTCs provides a substantial advancement for personalized PTT-triggered immunotherapy and has great clinical translational potential. [ABSTRACT FROM AUTHOR]

Bioorthogonal reactions involving transition metals have diversified applications in imaging, drug development, chemical catalysis and other fields. Transition metals used to catalyze the bioorthogonal reaction mainly include ruthenium, palladium, copper, and gold. However, the great potential for translational applications of bioorthogonal reaction needs to be further expanded and their reaction efficiency should be improved. Therefore, it is an urgent need for the development of this field to find more suitable catalysts to efficiently catalyze existing biological orthogonal reactions and expand the types of biological orthogonal reactions. Thus, this review not only summarizes those transition metal complexes-based catalysts participating in bioorthogonal reaction and some bioorthogonal reactions involving transition metals inside the cells, but also sheds light into the discovery of new transition metal complexes and their future development in applications. [ABSTRACT FROM AUTHOR]

Many metal complexes not only had excellent cytotoxic antitumor effects but also could function as a positive immunomodulatory to improve antitumor effects by modifying the local tumor microenvironment. Herein, a dual-target nanotherapeutics (MP3/ACPP/AE105@NPs) with uPAR targeting and tumor microenvironment-responsive ability was developed by using AE105 as the targeting ligand and ACPP as the tumor microenvironment-responsive peptide to locate the metal complex to cells. Assisted by the surface modification, MP3/ACPP/AE105@NPs demonstrated excellent cellular uptake of the drugs in in vitro experiments, thereby enhancing the therapeutic utility of the loaded metal complex. The nanotherapeutics induced the excessive ROS generation by inhibiting the activity of TrxR and modulated those proteins which were related to metastasis through inhibiting ERK/AKT activation mediated by FAK in MDA-MB-231 cells. This nanotherapeutics could also significantly improve the therapeutic benefits in vivo accompanied by reduced toxic side effects. Importantly, MP3/ACPP/AE105@NPs treatment stimulated immunotherapeutic response, which was indicated by the activation of tumor-infiltrated cytotoxic T cells, and improved the maturation of dendritic cells (DCs), and the proliferation-inhibitory effect of tumor-associated M2 macrophages. Taken together, the results suggested that this dual-targeted nanotherapeutics offered new opportunities for boosting the synergistic treatment of breast cancer with chemotherapy and immunotherapy. This study provided a universality method for synthesis of nanotherapeutics for encapsulating various metal complexes. The dual-targeted MP3/AA@NPs greatly improved discrimination between cancer cells and normal cells, moreover, MP3/AA@NPs displayed good in vitro and in vivo antitumor activities as well as stimulating immunotherapeutic response. [ABSTRACT FROM AUTHOR]

Radiotherapy is one of the main therapeutic methods for cancers; however, nonselective killing of normal cells and tumor cells by X-ray inevitably results in toxicity and side effects. Developing low-toxicity and high-efficiency radiosensitizers to reduce the practical dose of X-ray is a promising approach to overcoming these side effects. Here, we report the use of carboxylate-containing organic ligands to construct one-dimensional high-Z lanthanide chains for efficient response to X-ray. The one-dimensional lanthanide chains are stacked through weak interactions to form coordination nanoframeworks in the presence of polyethylenimine (PEI). The morphology and activity of the synthesized nanoframeworks can be regulated through selenium atom engineering. This study presents a promising approach for effective radiotherapy through selenium-engineering stable lanthanide nanoframeworks with precise coordination structures as radiosensitizers to mitigate X-ray side effects. [ABSTRACT FROM AUTHOR]

The search of highly efficient drugs for overcoming cancer drug resistance continues to be a challenge for scientists. Constructing a metal drug based in situ oxidation-state transition system to disturb the redox balance in cancer cells is a promising approach for overcoming cancer drug resistance. Inspired by natural redox-active copper enzyme centers, we developed a Cu(I)-Cu(II) in situ transition system in this work. Through atom engineering, we fine-tuned the thermodynamic stability of this system to investigate its anticancer activity The results indicated that the synthetic Cu(I)-Cu(II) system could under-go in situ transition in vitro and in vivo, to disrupt the intracellular redox balance and trigger mitochondrial dysfunction and G2/M arrest, leading to apoptosis and overcoming cancer drug resistance This study presents a feasible way to overcome cancer drug resistance by designing an in situ oxidation-state transition metal drug system. [ABSTRACT FROM AUTHOR]

Herein a series of combretastatin A-4 (CA-4) analogues with aggregation-induced emission characteristics (compounds a1–a19) were rationally designed and synthesized. The research results showed that the mechanism of AIE of a1–a19 could be attributed to the dual function of the restriction of intramolecular motion (RIM) and J-aggregate formation. Furthermore, the detailed investigation on the action mechanisms revealed that a19 diffused from lysosomes into the cytoplasm, and then targeted the colchicine binding site to induce cell cycle arrest and apoptosis in cancer cells. These results provide new ideas and impetus for the rational design of CA-4 analogues. [ABSTRACT FROM AUTHOR]

Highlights: 2D Sn nanosheets (SnNSs) were prepared through the combination of cryogenic exfoliation and liquid-phase exfoliation. The functionalized 2D SnNSs have good stability, superior biocompatibility, high photothermal conversion efficiency, and multimode imaging capability.Stanene (Sn)-based materials have been extensively applied in industrial production and daily life, but their potential biomedical application remains largely unexplored, which is due to the absence of the appropriate and effective methods for fabricating Sn-based biomaterials. Herein, we explored a new approach combining cryogenic exfoliation and liquid-phase exfoliation to successfully manufacture two-dimensional (2D) Sn nanosheets (SnNSs). The obtained SnNSs exhibited a typical sheet-like structure with an average size of ~ 100 nm and a thickness of ~ 5.1 nm. After PEGylation, the resulting PEGylated SnNSs (SnNSs@PEG) exhibited good stability, superior biocompatibility, and excellent photothermal performance, which could serve as robust photothermal agents for multi-modal imaging (fluorescence/photoacoustic/photothermal imaging)-guided photothermal elimination of cancer. Furthermore, we also used first-principles density functional theory calculations to investigate the photothermal mechanism of SnNSs, revealing that the free electrons in upper and lower layers of SnNSs contribute to the conversion of the photo to thermal. This work not only introduces a new approach to fabricate 2D SnNSs but also establishes the SnNSs-based nanomedicines for photonic cancer theranostics. This new type of SnNSs with great potential in the field of nanomedicines may spur a wave of developing Sn-based biological materials to benefit biomedical applications. [ABSTRACT FROM AUTHOR]

Gracilaria is the second most productive genus of mariculture seaweeds after Laminaria in China. It is important to increase its economic value. The purpose of this study was to document the accumulation and biotransformation of selenium in Gracilaria lemaneiformis. The seaweed was cultured for 12 days in medium containing from 0 to 2000 mg L−1 selenite. At concentrations lower than 750 mg L−1, seaweed growth was promoted and the amount of chlorophyll a decreased. The organic Se content in the seaweed was over 80% in all groups and was as much as 400 μg g−1 of dry weight. Se enrichment induced a decrease in the activities of superoxide dismutase in the seaweed cells. These results suggest that G. lemaneiformis is tolerant to Se and prevents phytotoxicity by altering various metabolic processes. Furthermore, this seaweed exhibits great potential to transform inorganic Se into the organic form and therefore could be a safe candidate for the production of Se-enriched functional food. [ABSTRACT FROM AUTHOR]

Rational design of smart nanosystems with high biological safety is a critical milestone for realizing precise imaging-guided cancer theranostics. Herein, a bioinspired nanosystem was designed by camouflaging SPIO@DOX-ICG nanoparticles with cancer cell membrane (CCM) to realize precise cancer treatment through simultaneous chemotherapy, hyperthermia-therapy, and radiotherapy. CCM surface decoration preserves the cancer adhesion molecules and surface antigens in the nanosystem, endowing the nanosystem with tumor-homing ability and high biocompatibility. Guided by dual-modal imaging, the nanosystem specifically accumulated in the tumor region and achieved synergistic anticancer effects after combined treatment, without causing toxic side effects in major organs. Interestingly, the combined treatment also antagonized tumor hypoxia and reprogrammed the polarization of tumor associated macrophages to the antitumor M1 phenotype. Taken together, this study offers a smart strategy for designing a bioinspired tumor-homing nanosystem for precise cancer therapy. A bioinspired nanosystem of cancer cell membrane-camouflaged SPIO@DOX-ICG nanoparticles was fabricated to realize precise cancer treatment by simultaneous chemotherapy, hyperthermia-therapy, and radiotherapy. The nanosystem achieved synergistic anticancer effects by antagonizing tumor hypoxia and reprograming the polarization of tumor associated macrophages to anti-tumor M1 phenotype, without causing toxic side effects on major organs. Non-toxic nanoparticles that can target tumors and aid the treatment of cancer have been developed and tested by scientists in China. Nanoparticles injected into the body can improve the resolution of medical scans, or carry therapeutic drugs through the body. Nanoparticles that can achieve both simultaneously are particularly important because they enable multiple different types of therapy. Tianfeng Chen from Jinan University, Zhuang Liu from Soochow University and co-workers made nanoparticles containing the chemotherapeutic drug doxorubicin and the imaging agent indocyanine green, which they coated with membrane from a cancer cell. These nanoparticles accumulated in mouse tumors where they could both deliver drugs for chemotherapy and act as targets for hyperthermia therapy and radiotherapy, all without having any toxic side effects on major organs. [ABSTRACT FROM AUTHOR]

Enrichment of selenium (Se) by seaweed is of great significance for mariculture. In this study, the green alga Ulva fasciata was cultured with a selenite (NaSeO) concentration from 0 to 1,250 mg L. Se accumulation in the algal biomass was linearly related to NaSeO concentration in the culture medium. Lower Se concentrations (≤750 mg L) increased the activities of guaiacol peroxidase (GPX), catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) and the content of photosynthetic pigments, and as well induced lipid peroxidation (LPO) and intracellular reactive oxygen species (ROS) levels. Meanwhile, the cell growth rate and concentrations of organic Se increased. In contrast, these changes were the opposite in U. fasciata exposed to Se concentrations higher than 750 mg L. In all cases, Se- Ulva was able to remove inorganic nutrients effectively. Therefore, U. fasciata is tolerant to Se, and Se- Ulva has potential as a source of antioxidative food and an effective control of eutrophication. [ABSTRACT FROM AUTHOR]

Ruthenium-based complexes have emerged as promising antitumor and antimetastatic agents during the past decades. However, the limited understanding of the antimetastatic mechanisms of these agents is a roadblock to their clinical application. Herein, we reported that, RuPOP, a ruthenium polypyridyl complex with potent antitumor activity, was able to effectively inhibit growth and metastasis of MDA-MB-231 cells and synergistically enhance TRAIL-induced apoptosis. The selective intracellular uptake and cytotoxic effect of RuPOP was found associated with transferring receptor (TfR)-mediated endocytosis. Further investigation on intracellular mechanisms reveled that RuPOP notably suppressed FAK-mediated ERK and Akt activation. Pretreatment of cells with ERK inhibitor (U0126) and PI3K inhibitor (LY294002) significantly potentiated the inhibitory effect of RuPOP on cell growth, migration and invasion. Moreover, the alternation in the expression levels of metastatic regulatory proteins, including uPA, MMP-2/-9, and inhibition of VEGF secretion were also observed after RuPOP treatment. These results demonstrate the inhibitory effect of RuPOP on the growth and metastasis of cancer cells and the enhancement of TRAIL-induced apoptosis though suppression of FAK-mediated signaling. Furthermore, RuPOP exhibits the potential to be developed as a metal-based antimetastatic agent and chemosensitizer of TRAIL for the treatment of human metastatic cancers. [ABSTRACT FROM AUTHOR]

Background: The impact of sarcopenia on the outcome of gastrointestinal (GI) oncological patients is still controversial. We aim to discuss the prevalence of sarcopenia and its relation to the oncological outcome., Methods: Embase, Medline, PubMed, and the Cochrane library were systematically searched for related keywords. Studies using CT to assess sarcopenia and evaluate its relationship with the outcome of GI oncological patients were included. Long-term outcomes, including overall survival and disease-free survival, were compared by hazard ratios (HRs) with 95% confidence intervals (CIs). Short-term outcomes, including total complications and major complications (Clavien-Dindo ≥IIIa) after curable surgery, were compared by the risk ratio (RR) and 95% CI., Results: A total of 70 studies including 21,875 patients were included in our study. The median incidence of sarcopenia was 34.7% (range from 2.1 to 83.3%). A total of 88.4% of studies used skeletal muscle index (SMI) in the third lumbar level on CT to define sarcopenia, and a total of 19 cut-offs were used to define sarcopenia. An increasing trend was found in the prevalence of sarcopenia when the cut-off of SMI increased (β = 0.22, 95% CI = 0.12-0.33, p < 0.001). The preoperative incidence of sarcopenia was associated both with an increased risk of overall mortality (HR = 1.602, 95% CI = 1.369-1.873, P < 0.001) and with disease-free mortality (HR = 1.461, 95% CI = 1.297-1.646, P < 0.001). Moreover, preoperative sarcopenia was a risk factor for both total complications (RR = 1.188, 95% CI = 1.083-1.303, P < 0.001) and major complications (RR = 1.228, 95% CI = 1.042-1.448, P = 0.014)., Conclusion: The prevalence of sarcopenia depends mostly on the diagnostic cut-off points of different criteria. Preoperative sarcopenia is a risk factor for both long-term and short-term outcomes.