Fig. 6

In vitro and in vivo delivery of STING agonists. The plasma membrane is a selectively permeable barrier that prevents cytoplasmic entry of large or hydrophilic molecules, including naked cyclic dinucleotides (CDNs) (1). In vitro (blue background) delivery of dinucleotide compounds could be achieved by the liposomal delivery system (2), or via reversible permeabilisation of plasma membrane to allow diffusion of naked CDNs into the cytoplasm (3). Recently designed YSK05-containing liposomes (4) could carry c-di-GMP across plasma membranes to induce DDX41-mediated STING activation as well as enhance the expression of MHC class I molecules and T cell co-stimulatory receptors (not demonstrated), and thus it is considered to be a potential adjuvant for cancer immunotherapy. In addition, the polyethyleneimine/ hyaluronic acid (LH) hydrogel-based vesicles use phagocytosis to deliver both STING ligands and antibody-stimulating agents such as ovalbumin (dark triangles) to cells (5), and enhance both STING-dependent innate immunity and MHC class II-activated adaptive immunity to suppress cancer growth. Both YSK05 particles and LH hydrogel-based particles have been tested in vivo (green background) to stall tumour progression in mice (6)