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Advancements in nanotechnology and molecular biology have promoted the development of a diverse range of models to intervene in various disorders (from diagnosis to treatment and even theranostics). Manganese dioxide nanosheets (MnO2 NSs), a typical two-dimensional (2D) transition metal oxide of nanomaterial that possesses unique structure and distinct properties have been employed in multiple disciplines in recent decades, especially in the field of biomedicine, including biocatalysis, fluorescence sensing, magnetic resonance imaging and cargo-loading functionality. A brief overview of the different synthetic methodologies for MnO2 NSs and their state-of-the-art biomedical applications is presented below, as well as the challenges and future perspectives of MnO2 NSs.

Arsenic trioxide (ATO) has been shown to have antitumor effect in different tumors, although the underlying mechanisms are not fully understood. Autophagy plays a critical role in tumorigenesis and cancer therapy and has been found to be activated by ATO in different cells. However, the role of autophagy in the antitumor effect of ATO has not yet been elucidated. In this study, we investigated the role of autophagy in the antiangiogenic effect of ATO in human umbilical vein endothelial cells (HUVECs) in vitro and its underlying mechanism. Our data showed that ATO suppresses angiogenesis and induces autophagy in HUVECs through upregulation of forkhead box protein O3 (FoxO3a). Co-incubated with autophagy inhibitor or knockdown of FoxO3a effectively inhibited ATO-induced autophagy and reversed the antiangiogenic effect of ATO, indicating that ATO-induced autophagy plays an antiangiogenic role in HUVECs. Our results highlight the importance of autophagy in the antiangiogenic effect of ATO and provide an improved understanding of the function of ATO.

A novel form of magnetic bead, namely antibody-coated magnetic lipid nano-vehicle (AMLV), was synthesized by embedding Fe3O4 nanoparticles into an amphiphilic antibody-modified liposome as a high-performance circulating tumor cell (CTC) hunter. The CTC capture performance of AMLV was validated based on an enlarged patient sample (including 318 colorectal, 78 breast, 77 lung and 55 liver cancer patients) with high detection rate. The preliminary comparison with Cellsearch was also conducted, indicating that the cell membrane-semblance AMLVEpCAM showed higher capture performance for different kinds of EpCAM-expressed circulating tumor cells in the peripheral blood (4.4 ± 1.2-fold for AMLVEpCAM vs CellsearchTM, n=5, P

Purpose Castration resistance prostate cancer patients showing resistance to the androgen deprivation therapy always have low five-year survival rate and worse prognosis. A responsive NIR fluorescent probe was designed to report the androgen dependence and monitor the development of castration resistance for prostate cancer. Methods Intratumoral H2S in prostate cancer was closely related to castration resistance. A H2S-responsive NIR probe (HM) was developed as a dependent indicator to report the androgen dependence of prostate cancer. The specificity of HM to H2S and the influence of normal intracellular substrates to the response between H2S and HM were determined. Cell/in vivo animal imaging were performed on PC-3 and LnCAP cell/tumor bearing mice, which presented with androgen independence and androgen dependence, respectively. Results When HM responded to H2S, strong fluorescence at 770 nm could be rapidly turned on in 5 min with the stokes shift as large as 200 nm. The recognition between HM and H2S showed high specificity. Neither other common substrates showed capacity to turn on HM's fluorescence, nor their existence demonstrated competition. The fluorescence intensity was linearly dependent to the H2S concentration and the limited of detection was 0.15 μM. When HM was applied to PC-3/LNCaP prostate cancer cell and tumor, the intracellular and intratumoral H2S could be clearly imaged and monitored. Conclusion HM showing obvious fluorescent behaviors in androgen dependence and independence prostate tumor, which could work as an indicator to reported the androgen dependence of prostate cancer and monitor the development of castration resistance.

Intracellular cysteine and glutathione was deemed as the most important reductants in the cell and played significant roles in the cellular homeostasis and redox adjustment. Here we developed a NIR fluorescent probe (HI) to detect and report the intracellular cysteine and glutathione, and monitor the development of the drug resistance of tumor. HI with both excited wavelength and emitting wavelength located within near infrared area showed no fluorescence in the normal physiological environment. However, when HI responded to cysteine and glutathione, strong NIR fluorescence could be turned on, which was linear dependent to the cysteine concentrations and the limited of detection was 0.18 μM. The response between HI and cysteine/glutathione demonstrated high specificity and no other amino acids showed influence or competition. The HPLC identification of the recognition results confirmed the response of acryloyloxy on the HI and active sulfhydryl on the cysteine/glutathione. DFT calculation of the HOMO and LUMO energy before and after response revealed the intramolecular charge transfer mechanism that induced the generation of the fluorescence. When HI was incubated with PATU-8988 and PATU-8988/Fu cell, the intracellular cysteine and glutathione could be clearly imaged and monitored by the enhanced fluorescence. Meanwhile, when HI was applied to the tumor-bearing mice, the drug resistance of tumor could be monitored and reported.

The incidence of thyroid disorders, which are common endocrine diseases, has rapidly increased in recent years. However, the etiology and pathogenesis of these disorders remain unclear. Phosphatase and tension homolog (PTEN) is a dual-specific phosphatase that is associated with multiple thyroid disorders; however, the role of PTEN in thyroid disorders remains unknown. In the present study, the human thyroid follicular epithelial cell line Nthy-Ori 3-1 was used to determine the role of PTEN in thyroid disorders. PTEN expression was knocked down using a PTEN-specific short hairpin RNA. Western blotting was subsequently used to determine protein expression, the Matrigel tube formation assay and iodide uptake assay were applied for evaluating the morphology and function of thyroid cells. The results showed that PTEN knockdown decreased the protein expression of paired box 8 (PAX8). The morphology and tubular-like growth pattern of thyroid cells were therefore disrupted, and restoration of PAX8 expression reversed these effects. Furthermore, PTEN-knockdown decreased the expression of specific thyroid proteins (thyroglobulin, TG; thyroid peroxidase, TPO; and sodium/iodide symporter, NIS) and inhibited the iodide uptake ability of thyroid cells by downregulating PAX8, suggesting that PTEN deficiency may impair the function of thyroid cells. In conclusion, the present study reported an important function of PTEN in normal thyroid cells and identified the involvement of PAX8. These results may improve understanding of the role of PTEN in the pathogenesis of thyroid disorders.

Proper spindle formation and accurate chromosome segregation are essential for ensuring mitotic fidelity. Phosphatase and tensin homolog (PTEN) is a multifunctional protein, which is able to maintain the stability of the genome and chromosomes. The present study described an essential role of PTEN in regulating chromosome segregation to prevent gross genomic instability via regulation of mitotic arrest deficient 2 (MAD2). PTEN knockdown induced cell cycle arrest and abnormal chromosome segregation, which manifested as the formation of anaphase bridges, lagging chromosomes and premature chromatid separation. In addition, MAD2 was identified as a potential target of PTEN. Furthermore, the present study revealed that PTEN knockdown resulted in MAD2 degradation via the ubiquitin‑proteasomal pathway, while restoration of MAD2 expression partially ameliorated the mitotic defects induced by PTEN loss. The results from the present study proposed a novel mechanism by which PTEN maintains chromosome stability.

Arsenic trioxide (As2O3) has been used clinically for the treatment of acute promyelocytic leukemia and some solid tumors. However, the mechanisms of its anti-tumor effects are still elusive. Angiogenesis is a key process for tumor initiation, and increasing evidence has supported the role of anti-angiogenesis caused by arsenic in tumor suppression, although the detailed mechanism is not well understood. In the present study, we found that As2O3 significantly inhibited the angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro, and this was mediated by the upregulation of FoxO3a. Knockdown of FoxO3a could restore the angiogenic ability of HUVECs. Moreover, vascular endothelial cell-specific knockout of FoxO3a in mice could disrupt the anti-angiogenesis effect of As2O3 and endow the tumors with resistance to As2O3 treatments. Our results revealed a new mechanism by which As2O3 suppresses angiogenesis and tumor growth.