Immunotherapy is one of the key strategies for cancer treatment. The cGAS-cGAMP-STING-IRF3 pathway of cytosolic DNA sensing plays a pivotal role in antiviral defense. We report that the STING activator cGAMP possesses significant antitumor activity in mice by triggering the STING-dependent pathway directly. cGAMP enhances innate immune responses by inducing production of cytokines such as interferon-β, interferon-γ, and stimulating dendritic cells activation, which induces the cross-priming of CD8+ T cells. The antitumor mechanism of cGAMP was verified by STING and IRF3, which were up-regulated upon cGAMP treatment. STING-deficiency dramatically reduced the antitumor effect of cGAMP. Furthermore, cGAMP improved the antitumor activity of 5-FU, and clearly reduced the toxicity of 5-FU. These results demonstrated that cGAMP is a novel antitumor agent and has potential applications in cancer immunotherapy.

The structure-antibacterial activity relationship between the small molecular compounds and polymers are still elusive. Here, imidazolium-type ionic liquid (IL) monomers and their corresponding poly(ionic liquids) (PILs) and poly(ionic liquid) membranes were synthesized. The effect of chemical structure, including carbon chain length of substitution at the N3 position and charge density of cations (mono- or bis-imidazolium) on the antimicrobial activities against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was investigated by determination of minimum inhibitory concentration (MIC). The antibacterial activities of both ILs and PILs were improved with the increase of the alkyl chain length and higher charge density (bis-cations) of imidazolium cations. Moreover, PILs exhibited lower MIC values relative to the IL monomers. However, the antibacterial activities of PIL membranes showed no correlation to those of their analogous small molecule IL monomers and PILs, which increased with the charge density (bis-cations) while decreasing with the increase of alkyl chain length. The results indicated that antibacterial property studies on small molecules and homopolymers may not provide a solid basis for evaluating that in corresponding polymer membranes.

Pyrrolidinium-type small molecule ionic liquids (ILs), poly(ionic liquid) (PIL) homopolymers, and their corresponding PIL membranes were synthesized and used for antibacterial applications. The influences of substitutions at the N position of pyrrolidinium cation on the antimicrobial activities against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were studied by minimum inhibitory concentration (MIC). The antibacterial efficiency of both the small molecule ILs and PIL homopolymers increased with the increase of the alkyl chain length of substitutions. Furthermore, PIL homopolymers show relatively lower MIC values, indicating better antimicrobial activities than those of the corresponding small molecule ILs. However, the antibacterial properties of the PIL membranes are contrary to corresponding ILs and PIL homopolymers, which reduce with the increase of alkyl chain length. Furthermore, the resultant PIL membranes show excellent hemocompatibility and low cytotoxicity toward human cells, demonstrating clinical feasibility in topical applications.

The development of materials with intrinsically antimicrobial activities has attracted great interest. Herein, we report the synthesis of free-standing and robust poly(ionic liquid) (PIL) membranes with high antibacterial activities by in situ photo-cross-linking of an ionic liquid monomer and followed by anion-exchange with an amino acid (L-proline (Pro) or L-tryptophan (Trp)). The resultant PIL-based membranes with excellent robustness exhibit high antimicrobial properties against both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) and present no significant hemolysis and cytotoxicity toward human red blood and skin fibroblast cells, as well as low adsorption of bovine serum albumin. The synthesized PIL-Trp membranes exhibit the highest antibacterial efficiency due to the synergistic attributes of both imidazolium cation and Trp − anion. Furthermore, all the PIL-based membranes exhibit long-term antibacterial stability, which demonstrates clinical feasibility in topical applications.

Herein, a series of quaternary ammonium (Qa) or imidazolium (Im) cation-based poly(ionic liquid) (PIL) membranes and their corresponding zinc ion coordinated PIL membranes were synthesized. The effects of chemical structure, including organic cations, alkyl side chain of substitution, and zinc atoms on the antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Candida albicans were investigated. The Zn-containing PIL membranes show higher antibacterial activities compared to those of pristine PIL membranes due to the synergistic attributes of both organic cations (Qa or Im) and zinc atoms. A wound healing test using methicillin-resistant S. aureus infected mouse as the model further demonstrated that zinc ion coordinated PIL membranes were antibacterially active, biologically safe, and may have potential application as an antimicrobial wound dressing in a clinical setting.

Imidazolium-type metal-containing ionic liquid (IL) monomers and their corresponding poly(ionic liquid) (PIL) membranes coordinated with CuCl 2 (PILM-Cu), FeCl 3 (PILM-Fe), or ZnCl 2 (PILM-Zn) were synthesized. The effect of metal ions on the antimicrobial activities against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was investigated. Compared with pristine PILM-Br membrane, PILM-Cu, PILM-Fe, and PILM-Zn membranes exhibit enhanced antibacterial activities due to the attributes of both imidazolium cations and metal-containing anions. Furthermore, all of the metal-containing PIL membranes present low hemolysis toward human red blood cell and high long-term antibacterial stability, even after immersion in water for 90 days, demonstrating clinical feasibility in topical applications.

Polycationic polymers have been widely used as antimicrobial materials because of their broad spectrum activity and potential use as new antibiotics. Herein, we report the synthesis of polyanionic antimicrobial membranes by in situ photo-cross-linking of a sulfate based anionic monomer, followed by cation-exchange with organic (quaternary ammonium or imidazolium) or metal (Ag, Cu, Fe, Zn, Na, K) cations. The resultant polyanionic membranes show high and broad spectrum antibacterial activities against both bacteria (Escherichia coli, Staphylococcus aureus) and fungi (Candida albicans ). In addition, the polyanionic antimicrobial membranes efficiently inhibited the formation of biofilms by SC5314 and its crk1 gene deleted (Δcrk1) C. albicans strains. Furthermore, the synthesized polyanionic membranes exhibit good blood compatibility, low cytotoxicity and long-term antibacterial stability, demonstrating safe antimicrobial materials in the application of healthcare.

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