ABSTRACT
BACKGROUND: The activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway has attracted great attention for its ability to up-regulate innate immune response and thus enhance cancer immunotherapy. However, many STING agonists limit the further advancement of immunotherapy due to weak tumor responsiveness or low activation efficiency. The responsive and effective activation of cGAS-STING signaling in tumors is a highly challenging process. METHODS: In this study, a manganese-based nanoplatform (MPCZ NPs) was constructed that could responsively and efficiently generate more manganese ions (Mn2+) and reactive oxygen species (ROS) to activate cGAS-STING signaling pathway. Briefly, manganese dioxide (MnO2) was loaded with zinc protoporphyrin IX (ZPP) molecule and coated by polydopamine (PDA) embedded with NH4HCO3 to obtain MPCZ NPs. Additionally, MPCZ NPs were evaluated in vitro and in vivo for their antitumor effects by methyl thiazolyl tetrazolium (MTT) assay and TUNEL assays, respectively. RESULTS: In this system, tumor responsiveness was achieved by exogenous (laser irradiation) and endogenous (high levels GSH) stimulation, which triggered the collapse or degradation of PDA and MnO2. Moreover, the release of Mn2+ augmented the cGAS-STING signaling pathway and enhanced the conversion of hydrogen peroxide (H2O2) to hydroxyl radical (·OH) under NIR laser irradiation. Furthermore, the release of ZPP and the elimination of GSH by MPCZ NPs inhibited HO-1 activity and prevented ROS consumption, respectively. CONCLUSIONS: This adopted open source and reduce expenditure strategy to effectively generate more ROS and Mn2+ to responsively activate cGAS-STING signaling pathway, providing a new strategy for improving immunotherapy.
ABSTRACT
Porous conjugated polymers offer enormous potential for energy storage because of the combined features of pores and extended π-conjugated structures. However, the drawbacks such as low pore volumes and insolubilities of micro- and mesoporous conjugated polymers restrict the loading of electroactive materials and thus energy storage performance. Herein, we report the synthesis of iron-doped macroporous conjugated polymers for hosting sulfur as the cathode of high-performance lithium-sulfur (Li-S) batteries. The macroporous conjugated polymers are synthesized via in situ growth of poly(3-hexylthiophene) (P3HT) from reduced graphene oxide (RGO) sheets, followed by gelation of the composite (RGO- g-P3HT) in p-xylene and freeze-drying. The network structures of the macroporous materials can be readily tuned by controlling the chain length of P3HT grafted to RGO sheets. The large pore volumes of the macroporous RGO- g-P3HT materials (ca. 34 cm3 g-1) make them excellent frameworks for hosting sulfur as cathodes of Li-S batteries. Furthermore, incorporation of Fe into the macroporous RGO- g-P3HT cathode results in reduced polarization, enhanced specific capacity (1,288, 1,103, and 907 mA h g-1 at 0.05, 0.1, and 0.2 C, respectively), and improved cycling stability (765 mA h g-1 after 100 cycles at 0.2 C). Density functional theory calculations and in situ characterizations suggest that incorporation of Fe enhances the interactions between lithium polysulfides and the P3HT framework.
ABSTRACT
We demonstrated the synthesis and directed self-assembly (DSA) of poly(styrene-b-(lactic acid-alt-glycolic acid)) (PS-b-PLGA). Lamellae-forming PS-b-PLGAs with a range of molecular weights were synthesized by ring-opening polymerization (ROP) of LGA (d,l-3-methyl-1,4-dioxane-2,5-dione) from hydroxy-terminated polystyrene (PS-OH) with stannous octoate as the catalyst and characterized by 1H NMR spectroscopy, GPC, DSC, TGA, SAXS, and rheometry. The order-disorder transition temperatures (TODT) of four PS-b-PLGA block copolymers were determined by temperature sweep measurements and verified by variable-temperature SAXS, which were used to determine the temperature dependence of χ. The χ value of PS-b-PLGA is twice as large as that of poly(styrene-b-racemic lactide) (PS-b-PDLLA) at 150 °C, while the surface energies (γ) of PS and PLGA are nearly equal. Thin films of PS-b-PLGA were successfully directed to assemble on stripe chemical patterns with a range of pattern periods (LS) upon thermal annealing. SEM analysis of the assembled films revealed that long-range ordered perpendicularly oriented lamellae were registered on chemical patterns with 2× density multiplication. These results qualify PS-b-PLGA as an attractive candidate for next-generation lithography with sub-10 nm resolution.
