Blocking energy metabolism of cancer cells and simultaneously stimulating the immune system to perform immune attack are significant for cancer treatment. However, how to potently deliver different drugs with these functions remains a challenge. Herein, we synthesized a nanoprodrug formed by a F127-coated drug dimer to inhibit glycolysis of cancer cells and alleviate the immunosuppressive microenvironment. The dimer was delicately constructed to connect lonidamine (LND) and NLG919 by a disulfide bond which can be cleaved by excess GSH to release two drugs. LND can decrease the expression of hexokinase II and destroy mitochondria to restrain glycolysis for energy supply. NLG919 can reduce the accumulation of kynurenine and the number of regulatory T cells, thus alleviating the immunosuppressive microenvironment. Notably, the consumption of GSH by disulfide bond increased the intracellular oxidative stress and triggered immunogenic cell death of cancer cells. This strategy can offer more possibilities to explore dimeric prodrugs for synergistic cancer therapy.

The chenopodiaceae Suaeda salsa L. is a leaf succulent euhalophyte. Shoots of the S. salsa are larger and more succulent when grown in highly saline environments. This increased growth and water uptake has been correlated with a large and specific cellular accumulation of sodium. S. salsa does not have salt glands or salt bladders on its leaves. Thus, this plant must compartmentalize the toxic Na(+) in the vacuoles. The ability to compartmentalize sodium may result from a stimulation of the proton pumps that provide the driving force for increased sodium transport into the vacuole. In this work, we isolated the cDNA of the vacuolar membrane proton-translocating inorganic pyrophosphatase (H(+) -PPase) from S. salsa. The SsVP cDNA contains an uninterrupted open reading frame of 2292 bp, coding for a polypeptide of 764 amino acids. Northern blotting analysis showed that SsVP was induced in salinity treated leaves. The activities of both the V-ATPase and the V-PPase in Arabidopsis overexpressing SsVP-2 is higher markedly than in wild-type plant under 200 mM NaCl and drought stresses. The Overexpression of SsVP can increase salt and drought tolerance of transgenic Arabidopsis.

Inducing immunogenic cell death (ICD) of cancer cells is an important method to improve the immunogenicity of tumor for enhanced cancer immunotherapy. Therefore, we discuss the ICD process and then...

Cancer immunotherapy aims to reinitiate the autoimmune responses for fighting cancer cells. Immunomodulators, such as immune vaccines, adjuvants, and immune checkpoint inhibitors, have been extensively developed to activate the immune response against cancer. However, it is disadvantageous to directly apply immunomodulators in cancer immunotherapy for the following reasons: (I) instability of immunomodulators; (II) immunomodulators easily cleared; (III) uncontrolled immune response. Many efforts have been made to overcome these drawbacks, among which loading immunomodulators by nanocarriers is a simple and effective method. Nanocarriers can not only protect immunomodulators from degradation but also control their release and extend their blood circulation time. Some nanocarriers can specifically enrich in immune cells or organs to regulate their connection to further modulate the immune system. Besides, response-type nanocarriers can also be designed as required to control the release of immunomodulators to reduce immune-related adverse events. Of note, nanocarriers with excellent photothermal or photodynamic properties play the crucial role in inducing immunogenic cell death for enhanced cancer immunotherapy. In this review, various nanocarriers and their bioapplications in cancer immunotherapy have been summarized. We outlined the inorganic, organic, and organic–inorganic hybrid nanocarriers and the designing of effective nanocarrier-based immune interventions. The prospects and drawbacks of nanocarriers were also further reviewed in this work. This review will provide vital guidance for the design and synthesis of nanocarriers for application in cancer immunotherapy.

A two-dimensional coordination polymer, [Co(mu(1,3)-SCN)(2)(mu(1,6)-dmpzdo)](n)() (where dmpzdo = 2,5-dimethylpyrazine-1,4-dioxide), has been synthesized and its crystal structure determined by X-ray crystallography. In the complex, the adjacent Co(II) ions are coordinated by mu(1,3)-SCN(-) bridging ligands which forms a one-dimensional chain along the a axis; the one-dimensional chains are further connected by mu(1,6)-dmpzdo bridging ligands which leads to the formation of a two-dimensional layer on the ac plane. The theoretical calculations reveal that a ferromagnetic coupling exists between the mu(1,3)-SCN(-) bridging Co(II) ions and an anti-ferromagnetic interaction between the mu(1,6)-dmpzdo bridging Co(II) ions, and the anti-ferromagnetic interaction is stronger than the ferromagnetic interaction. The fitting of the variable-temperature (34-300 K) magnetic susceptibilities reveals that there is an anti-ferromagnetic coupling between the bridging Co(II) ions with the magnetic coupling constant J = -3.52 cm(-1).