Hypoxia induces docetaxel resistance in triple-negative breast cancer via the HIF-1α/miR-494/Survivin signaling pathway.

Cytotoxic chemotherapy is the major strategy to prevent and reduce triple-negative breast cancer (TNBC) progression and metastasis. Hypoxia increases chemoresistance and is associated with a poor prognosis for patients with cancer. Based on accumulating evidence, microRNAs (miRNAs) play an important role in acquired drug resistance. However, the role of miRNAs in hypoxia-induced TNBC drug resistance remains to be clarified. Here, we found that hypoxia induced TNBC docetaxel resistance by decreasing the miR-494 level. Modulating miR-494 expression altered the sensitivity of TNBC cells to DTX under hypoxic conditions. Furthermore, we identified Survivin as a direct miR-494 target. Hypoxia upregulated survivin expression. In a clinical study, the HIF-1α/miR-494/Survivin signaling pathway was also active in primary human TNBC, and miR-494 expression negatively correlated with HIF-1α and survivin expression. Finally, in a xenograft model, both miR-494 overexpression and the HIF-1α inhibitor PX-478 increased the sensitivity of TNBC to DTX by suppressing the HIF-1α/miR-494/Survivin signaling pathway in vivo. In conclusion, treatments targeting the HIF-1α/miR-494/Survivin signaling pathway potentially reverse hypoxia-induced drug resistance in TNBC.

A new role of Yb3+-an energy reservoir for lanthanide upconversion luminescence.

Thus far, Yb3+ has usually served as a sensitizer to improve energy harvesting in lanthanide ion based luminescent materials. Herein, besides the well accepted character as a sensitizer, we revealed a new role of Yb3+, namely an energy reservoir, to improve the upconversion efficiency of several lanthanide activators. The energy cycling between lanthanide activator A3+ and energy reservoir Yb3+ is mainly responsible for the improvement. This energy cycling can facilitate energy utilization by A3+ for the generated upconversion luminescence. Specifically, this energy cycling not only alleviates the dissipation of energy produced at the intermediate level, needed to promote electrons to a higher energy level, but also provides an additional excited-state absorption route for A3+. The benefits of the proposed Yb3+ energy reservoir as well as the energy cycling mechanisms were verified using three representative activators, Nd3+, Tm3+, and Er3+. This study can open new possible avenues to exploit Yb3+ and enrich the available upconversion luminescence pathways of lanthanide ions.

Color tuning in a compact core-shell nanocrystal based on intense and high-purity green and red photon upconversion.

To date, color-tunable photon upconversion (UC) in a single nanocrystal (NC) still suffers from cumbersome structures. Herein, we prepared a compact two-layer NC with bright and high-purity red and green UC emission upon 980 and 1530 nm excitation, respectively. The effects of trace Tm3+ doping and inert-shell coating on the UC color and intensity were discussed. In addition, the color tuning via various dual-excitation configurations and the color stability with temperature and excitation intensity were demonstrated. The proposed UC NC, featuring compact structure and high-quality color tuning, can lower the synthesis time cost and difficulty of its kind and can find wide applications in multi-channel imaging, display devices, anti-counterfeiting, and so on.

Temperature-Independent Lifetime and Thermometer Operated in a Biological Window of Upconverting NaErF4 Nanocrystals.

Lifetime of lanthanide luminescence basically decreases with increasing the ambient temperature. In this work, we developed NaErF4 core-shell nanocrystals with compensation of the lifetime variation with temperature. Upconversion lifetime of various emissions remains substantially unchanged as increasing the ambient temperature, upon 980/1530 nm excitation. The concentrated dopants, leading to extremely strong interactions between them, are responsible for the unique temperature-independent lifetime. Besides, upconversion mechanisms of NaErF4 core-only and core-shell nanocrystals under 980 and 1530 nm excitations were comparatively investigated. On the basis of luminescent ratiometric method, we demonstrated the optical thermometry using non-thermally coupled 4F9/2 and 4I9/2 emissions upon 1530 nm excitation, favoring the temperature monitoring in vivo due to both excitation and emissions fall in the biological window. The formed NaErF4 core-shell nanocrystals with ultra-small particle size, highly efficient upconversion luminescence, unique temperature-independent lifetimes, and thermometry operated in a biological window, are versatile in applications such as anti-counterfeiting, time-domain manipulation, and biological thermal probes.