A Microfluidic Platform for Evaluating the Internalization of Liposome Drug Carriers in Tumor Spheroids.

The development of in vitro models recapitulating nanoparticle transport under physiological flow conditions is of great importance for predicting the efficacy of nanoparticle drug carriers. Liposomes are extensively used for drug delivery owing to their biocompatibility and biodegradability and the ability to carry both hydrophilic and hydrophobic compounds. Here, we used a library of liposomes with various dimensions and a microfluidic platform comprising a large array of uniformly sized breast cancer spheroids to explore size-dependent liposome internalization and retention in the spheroids under close-to-physiological interstitial conditions.

Activation of human STING by a molecular glue-like compound.

Stimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays a key role in the human innate immune response to infection and has been therapeutically exploited for its antitumor activity. The activation of STING requires its high-order oligomerization, which could be induced by binding of the endogenous ligand, cGAMP, to the cytosolic ligand-binding domain. Here we report the discovery through functional screens of a class of compounds, named NVS-STGs, that activate human STING.

Modulation of Kinase Activities In Vitro by Hepatitis C Virus Protease NS3/NS4A Mediated-Cleavage of Key Immune Modulator Kinases.

Hepatitis C Virus NS3/NS4A, a serine protease complex, has been found to interact with many host proteins and cause various adverse effects on cellular function and immune response. For example, the cleavage of important immune factors by NS3/NS4A has been suggested as a mechanism for the hepatitis C virus to evade innate immunity. The spectrum of susceptible substrates for NS3/NS4A cleavage certainly includes important immune modulator kinases such as IKKα, IKKβ, IKKε, and TBK1, as demonstrated in this paper.