Immunogenic cell death (ICD) is a way of reengaging the tumor-specific immune system. ICD can be induced by treatment with chemotherapeutics. However, only a limited number of drugs and other treatment modalities have been shown to elicit the biomarker responses characteristic of ICD and to provide an anticancer benefit in vivo. Here, we report a rationally designed redox-active Au­(I) bis-N-heterocyclic carbene that induces ICD both in vitro and in vivo. This work benefits from a synthetic pathway that allows for the facile preparation of asymmetric redox-active Au­(I) bis-N-heterocyclic carbenes.

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Insoluble aluminum salts such as aluminum (oxy)hydroxide are commonly used vaccine adjuvants. Recently, there is evidence suggesting that the adjuvant activity of aluminum salt-based materials is tightly related to their physico-chemical properties, including nanometer-scale size, shape with long aspect ratio, and low degree of crystallinity. Herein, for the first time, the bicontinuous reverse microemulsion (RM) technique was utilized to synthesize stick-like monodisperse aluminum (oxy)hydroxide nanoparticles with a long aspect ratio of ~10, length of ~80 nm and low degree of crystallinity (denoted as Al-nanosticks). Moreover, the relationship between the physico-chemical properties of Al-nanosticks and the bicontinuous RM was discussed. Compared to the commercial Alhydrogel®, which contains micrometer-scale aluminum oxyhydroxide particular aggregates with a moderate degree of crystallinity, the Al-nanosticks are more effective in adsorbing and delivering antigens (e.g. ovalbumin, OVA) into antigen-presenting cells, activating inflammasomes, and potentiating OVA-specific antibody responses in a mouse model. It is concluded that the aluminum (oxy)hydroxide nanosticks synthesized in the bicontinuous RM are promising new aluminum salt-based vaccine adjuvants.

The development of phosphonate-metal materials is tightly related to the advancement in their synthesis methods. Herein, using zoledronic acid (Zol), a bisphosphonate (bioacitve phosphonate with a ‘P-C-P’ structure), and calcium as model molecules, we applied the reverse microemulsion (RM) method to synthesize a series of Zol-Ca complexes. We comprehensively i) studied the relationship between RM conditions, including the component ratio of RM, co-surfactants, reaction time, reactant concentrations, reaction temperature, and the presence of a phospholipid, 1, 2-dioleoyl-sn-glycero-3-phosphate acid (DOPA), and the physical properties of the complexes synthesized (i.e. shape, size, uniformity, monodispersity and hydrophilicity/hydrophobicity), and ii) explored the underlying mechanism(s). To evaluate the biomedical application potential of the Zol-Ca complexes synthesized, one type of hydrophobic, DOPA-coated spherical Zol-Ca complexes (denoted as Zol-Ca@DOPA) was formulated into a PEGylated lipid-based nanoparticle formulation (i.e. Zol-Ca@bi-lipid NPs, ~24 nm in diameter). In a mouse model with orthotopic mammary tumors, the Zol-Ca@bi-lipid NPs significantly enhanced the distribution of Zol in tumors, as compared to free Zol. It is expected that the RM-based systhesis of (bis)phosphonate-metal materials with controllable physical properties will help expand their applications.