Target Profiling of an Iridium(III)-Based Immunogenic Cell Death Inducer Unveils the Engagement of Unfolded Protein Response Regulator BiP.

Clinical chemotherapeutic drugs have occasionally been observed to induce antitumor immune responses beyond the direct cytotoxicity. Such effects are coined as immunogenic cell death (ICD), representing a "second hit" from the host immune system to tumor cells. Although chemo-immunotherapy is highly promising, ICD inducers remain sparse with vague drug-target mechanisms. Here, we report an endoplasmic reticulum stress-inducing cyclometalated Ir(III)-bisNHC complex (1a) as a new ICD inducer, and based on this compound, a clickable photoaffinity probe was designed for target identification, which unveiled the engagement of the master regulator protein BiP (binding immunoglobulin protein)/GRP78 of the unfolded protein response pathway. This has been confirmed by a series of cellular and biochemical studies including fluorescence microscopy, cellular thermal shift assay, enzymatic assays, and so forth, showing the capability of 1a for BiP destabilization. Notably, besides 1a, the previously reported ICD inducers including KP1339, mitoxantrone, and oxaliplatin were also found to engage BiP interaction, suggesting the important role of BiP in eliciting anticancer immunity. We believe that the ICD-related target information in this work will help to understand the mode of action of ICD that is beneficial to designing new ICD agents with high specificity and improved efficacy.

One-step synthesis of Janus hydrogel via heterogeneous distribution of sodium α-linoleate driven by surfactant self-aggregation.

Janus adhesive hydrogels have one-sided adhesive properties and hold promising applications in the health care field. However, a simple method for synthesizing Janus hydrogels is still lacking. In this study, we introduce an innovative method to prepare Janus hydrogels by harnessing a fundamental phenomenon: the self-aggregation of surfactants at high concentrations at the water-air interface. By combining a small amount [0.8 to 3.2 weight %, relative to mass of acrylamide (AM)] of sodium α-linoleate (LAS) with AM through free radical polymerization, we have synthesized Janus adhesive hydrogels. The Janus hydrogels exhibit remarkable adhesive strength and adhesive differences, with the top side (84 J m-2) being 21 times stronger than the bottom side, also an excellent elongation rate. Through comprehensive experiments, including chemical composition, surface morphology, and molecular dynamics (MD) simulations, we thoroughly investigate the mechanisms of the hydrogel's heterogeneous adhesion. This study presents an easy, efficient, and innovative method for preparing one-sided adhesive hydrogels.

Identification of an Au(I) N-Heterocyclic Carbene Compound as a Bactericidal Agent Against Pseudomonas aeruginosa.

The opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa) causes infections that are difficult to treat, which is due to the bacterial resistance to antibiotics. We herein identify a gold(I) N-heterocyclic carbene compound as a highly potent antibacterial agent towards P. aeruginosa. The compound significantly attenuates P. aeruginosa virulence and leads to low tendency to develop bacterial resistance. The antibacterial mechanism studies show that the compound abrogates bacterial membrane integrity, exhibiting a high bactericidal activity toward P. aeruginosa. The relatively low cytotoxic compound has excellent therapeutic effects on both the eukaryotic cell co-culture and murine wound infection experiments, suggesting its potential application as a bactericidal agent to combat P. aeruginosa infection.