We find that core–shell particles consisting of a silica core surface functionalized with a noncrosslinked polymer shell efficiently spread at a liquid interface to form a two-dimensional polymer corona surrounding the core. Here, we capitalize on the distinct interfacial morphology of soft particles to design two-dimensional assemblies with structural complexity. Despite the elegance of this approach, its experimental realization has remained largely elusive. Based on such Jagla potentials, a wide variety of phases including cluster lattices, chains, and quasicrystals have been theoretically discovered. More than two decades ago, Jagla demonstrated that core–shell particles with two interaction length scales can form complex, nonhexagonal minimum energy configurations. However, the prevalence of hexagonal symmetries in such self-assembling systems limits its structural versatility. The two-dimensional self-assembly of colloidal particles serves as a model system for fundamental studies of structure formation and as a powerful tool to fabricate functional materials and surfaces.
Finally, we critically review the current status and new potential avenues for modulating T cell function in cancer immunotherapy using siRNA. We provide a timely and comprehensive overview of current and emerging delivery technologies used for siRNA transfection, discussing their strengths and weaknesses from a clinical as well as a manufacturing point-of-view. In this review, we briefly discuss the extracellular and intracellular delivery hurdles associated with siRNA therapy, in particular with regard to T cell targeting. As such, siRNA molecules have a newfound potential to improve the proliferation, survival, tumor infiltration and potency of T cells in cancer immunotherapy. The recent surge of adoptive cell therapies and development of new and potent delivery approaches has enabled efficient siRNA delivery to T cells both ex vivo and in vivo. Despite the current focus on small molecule- and antibody-based immune checkpoint inhibitors as well as T cell-directed delivery of mRNA and genome editing machinery, the application of siRNA involves important clinical advantages. Small interfering RNAs (siRNAs) offer the potential to sequence-specifically silence the expression of negative regulator genes in T cells in a transient manner, thereby releasing the block on anti-tumor responses. Nonetheless, a significant fraction of patients remain unresponsive largely due to the immunosuppressive tumor environment that blunts T cell activity.
The recent clinical success of adoptive T cell therapies and immune checkpoint inhibitors has demonstrated the strength of modulating T cell function in fighting cancer.
T lymphocytes are the major drivers of antitumor immunity.