Antigen-Capturing Dendritic-Cell-Targeting Nanoparticles for Enhanced Tumor Immunotherapy Based on Photothermal-Therapy-Induced In Situ Vaccination.

In situ vaccines have revolutionized immunotherapy as they can stimulate tumor-specific immune responses, with the cancer being the antigen source. However, the heterogeneity of tumor antigens and insufficient dendritic cells (DCs) activation result in low cancer immunogenicity and hence poor vaccine response. Herein, a new in situ vaccine composed of acid-responsive liposome-coated polydopamine (PDA) nanoparticles modified with mannose and loaded with resiquimod (R848) is designed to promote the efficacy of immunotherapy. The in situ vaccine can actively target the tumor site based on the decomposition of the liposome, while the PDA nanoparticles promote photothermal therapy and capture the immunogenic cell-death-induced tumor-associated antigens based on the adsorption effect of dopamine-mimetic mussels. The PDA nanoparticles, which are modified with a mannose ligand, target the DCs and release R848 for activated antigen presentation. As a result, the in situ vaccine not only effectively activates the maturation of the DCs but also significantly enhances their effect on cytotoxic T lymphocyte cells. Furthermore, the vaccine effectively inhibits the distant recurrence and metastasis of tumors via long-term immune memory effects. Therefore, the in situ vaccine provides a potential strategy for improving the efficacy of cancer immunotherapy.

Decreased expression of GLUT4 in male CG-IUGR rats may play a vital role in their increased susceptibility to diabetes mellitus in adulthood.

Rats with intrauterine growth retardation and catch-up growth (CG-IUGR) after birth show increased susceptibility to diabetes mellitus in adulthood. The expression of glucose transporter type 4 (GLUT4) decreases in female IUGR offspring rats with seminutrient restriction during pregnancy. However, the male CG-IUGR rats also display an increased susceptibility to diabetes mellitus in adulthood. Whether there is another factor, besides GLUT4, in male CG-IUGR rat that mediates their susceptibility to diabetes mellitus? The male IUGR rats with catch-up growth were selected as the research objects. CG-IUGR rats had an increased fasting blood glucose level, and increased serum total cholesterol, triglyceride and free fatty acid levels. Glucose tolerance test and insulin tolerance test showed higher glucose levels and much higher insulin levels after a glucose load in CG-IUGR. The mRNA and protein expressions of IRS-2 in liver tissue, and IRS-1 and GLUT4 in skeletal muscle in CG-IUGR rats were down-regulated, but only the GLUT4 down-regulation displayed strong negative correlations with the decreased glucose tolerance capability by Pearson's analysis. The methylation patterns of CpG islands in the promoter regions of IRS-1, IRS-2 and GLUT4 in CG-IUGR rats varied, which was not significantly correlated with their expressions. The male CG-IUGR rats showed decreased glucose tolerant capability, suggesting increased susceptibility to diabetes mellitus in adulthood. The GLUT4 down-regulation may play a vital role in the development of decreased glucose tolerance in male CG-IUGR rats. The methylation modification of the promoter region of GLUT4 does not appear to be involved in its expression.