The first mitochondrion-anchoring photosensitizer that specifically generates singlet oxygen ( O ) in mitochondria under white light irradiation that can serve as a highly effective radiosensitizer is reported here, significantly sensitizing cancer cells to ionizing radiation. An aggregation-induced emission luminogen (AIEgen), namely DPA-SCP, is rationally designed with α-cyanostilbene as a simple building block to reveal AIE, diphenylamino (DPA) group as a strong electron donating group to benefit red emission and efficient light-controlled O generation, as well as a pyridinium salt as the targeting moiety to ensure specific mitochondrial localization. The AIE signature endows DPA-SCP with the capacity to visualize mitochondria in a fluorescence turn-on mode. It is found that under optimized experimental condition, DPA-SCP with white light does not lead to apoptosis/death of cancer cells, whereas provides an elevated O environment in the mitochondria. More importantly, increasing intracellular level of O originated from mitochondria is demonstrated to be a generic method to enhance the radiosensitivity of cancer cells with a supra-additive synergistic effect of "0 + 1 > 1." Noteworthy is that "DPA-SCP + white light" achieves a high SER10 value of 1.62, which is much larger than that of the most popularly used radiosensitizers, gold nanoparticles (1.19), and paclitaxel (1.32).

A new drug concentration meter is developed. In vivo drug release can be monitored precisely via a self-indicating drug delivery system consisting of a new aggregation-induced emission thermoresponsive hydrogel. By taking the advantage of a self-indicating system, one can easily detect the depletion of drugs, and reinject to maintain a dosage in the optimal therapeutic window.

During metaphase, in response to improper kinetochore-microtubule attachments, the spindle assembly checkpoint (SAC) activates the mitotic checkpoint complex (MCC), an inhibitor of the anaphasepromoting complex/cyclosome (APC/C). This process is orchestrated by the kinase Mps1, which initiates the assembly of the MCC onto kinetochores through a sequential phosphorylation-dependent signalling cascade. The Mad1-Mad2 complex, which is required to catalyse MCC formation, is targeted to kinetochores through a direct interaction with the phosphorylated conserved domain 1 (CD1) of Bub1. Here, we present the crystal structure of the Cterminal domain of Mad1 (Mad1 CTD ) bound to two phosphorylated Bub1 CD1 peptides at 1.75 A resolution. This interaction is mediated by phosphorylated Bub1 Thr461, which not only directly interacts with Arg617 of the Mad1 RLK (Arg-Leu-Lys) motif, but also directly acts as an N-terminal cap to the CD1 a-helix dipole. Surprisingly, only one Bub1 CD1 peptide binds to the Mad1 homodimer in solution. We suggest that this stoichiometry is due to inherent asymmetry in the coiled-coil of Mad1 CTD and has implications for how the Mad1-Bub1 complex at kinetochores promotes efficient MCC assembly.