RESUMEN
Cancer immunotherapy has become a promising strategy. However, the effectiveness of immunotherapy is restricted in "cold tumors" characterized with insufficient T cells intratumoral infiltration and failed T cells priming. Herein, an on-demand integrated nano-engager (JOT-Lip) was developed to convert cold tumors to hot via "increased DNA damage and dual immune checkpoint inhibition" strategy. JOT-Lip was engineered by co-loading oxaliplatin (Oxa) and JQ1 into liposomes with T-cell immunoglobulin mucin-3 antibodies (Tim-3 mAb) coupled on the liposomal surface by metalloproteinase-2 (MMP-2)-sensitive linker. JQ1 inhibited DNA repair to increase DNA damage and immunogenic cell death (ICD) of Oxa, thus promoting T cells intratumoral infiltration. In addition, JQ1 inhibited PD-1/PD-L1 pathway, achieving dual immune checkpoint inhibition combining with Tim-3 mAb, thus effectively promoting T cells priming. It is demonstrated that JOT-Lip not only increased DNA damage and promoted the release of damage-associated molecular patterns (DAMPs), but also enhanced T cells intratumoral infiltration and promoted T cell priming, which successfully converted cold tumors to hot and showed significant anti-tumor and anti-metastasis effects. Collectively, our study provides a rational design of an effective combination regimen and an ideal co-delivery system to convert cold tumors to hot, which holds great potential in clinical cancer chemoimmunotherapy.
RESUMEN
@#As a new member of two-dimensional materials, black phosphorus has shown good application prospects in the fields of photoacoustic imaging, photothermal photodynamic therapy, and drug loading due to its excellent characteristics such as good biodegradability, biocompatibility, thickness-dependent tunable direct band-gap, and high surface-to-mass ratio. Because black phosphorus has the characteristics of easy oxidation and degradation, it is coated with relatively stable liposomes or polymeric materials to construct a black phosphorus-based drug delivery system, which shows great potential in tumor treatment and diagnosis and has become a new focus in drug delivery research. In this paper, we introduce the role of black phosphorus in tumor diagnosis and treatment in detail, and summarize the design of black phosphorus-based drug delivery system in recent years as well as its research progress in tumor diagnosis and treatment, in order to provide reference for the research and application of black phosphorus.
RESUMEN
The proteins and antigens of nine strains of Toxoplasma gondii were analyzed by SDS-PAGE and immunoblotting. These strains including RH strain, Zs-2 strain, CN strain and SHI, SH2, SH3, SH4, SH5, SH8 strains, were obtained from other laboratories or isolated from deformity fetus in our laboratory. SDS-PAGE analysis revealed that these strains were very close in the major bands of proteins and differences were observed only in part. There were common components in antigens of all strains using IgG antibody prepared from high-titre rabbit antisera raised against RH strain of Toxoplasma.
