Aggregation‐Induced Emission Gold Clustoluminogens for Enhanced Low‐Dose X‐ray‐Induced Photodynamic Therapy

The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.

The integrin family of cell adhesion receptors regulates a diverse array of cellular functions crucial to the initiation, progression and metastasis of solid tumours. The importance of integrins in several cell types that affect tumour progression has made them an appealing target for cancer therapy. Integrin antagonists, including the alphavbeta3 and alphavbeta5 inhibitor cilengitide, have shown encouraging activity in Phase II clinical trials and cilengitide is currently being tested in a Phase III trial in patients with glioblastoma. These exciting clinical developments emphasize the need to identify how integrin antagonists influence the tumour and its microenvironment.

A fundamental understanding of the luminescence of Au-thiolate nanoclusters (NCs), such as the origin of emission and the size effect in luminescence, is pivotal to the development of efficient synthesis routes for highly luminescent Au NCs. This paper reports an interesting finding of Au(I)-thiolate complexes: strong luminescence emission by the mechanism of aggregation-induced emission (AIE). The AIE property of the complexes was then used to develop a simple one-pot synthesis of highly luminescent Au-thiolate NCs with a quantum yield of ~15%. Our key strategy was to induce the controlled aggregation of Au(I)-thiolate complexes on in situ generated Au(0) cores to form Au(0)@Au(I)-thiolate core-shell NCs where strong luminescence was generated by the AIE of Au(I)-thiolate complexes on the NC surface. We were able to extend the synthetic strategy to other thiolate ligands with added functionalities (in the form of custom-designed peptides). The discovery (e.g., identifying the source of emission and the size effect in luminescence) and the synthesis protocols in this study can contribute significantly to better understanding of these new luminescence probes and the development of new synthetic routes.