Two-Pronged Intracellular Co-Delivery of Antigen and Adjuvant for Synergistic Cancer Immunotherapy.

Nanovaccines have emerged as promising alternatives or complements to conventional cancer treatments. Despite the progresses, specific co-delivery of antigen and adjuvant to their corresponding intracellular destinations for maximizing the activation of antitumor immune responses remains a challenge. Herein, a lipid-coated iron oxide nanoparticle is delivered as nanovaccine (IONP-C/O@LP) that can co-deliver peptide antigen and adjuvant (CpG DNA) into cytosol and lysosomes of dendritic cells (DCs) through both membrane fusion and endosome-mediated endocytosis. Such two-pronged cellular uptake pattern enables IONP-C/O@LP to synergistically activate immature DCs. Iron oxide nanoparticle also exhibits adjuvant effects by generating intracellular reactive oxygen species, which further promotes DC maturation. IONP-C/O@LP accumulated in the DCs of draining lymph nodes effectively increases the antigen-specific T cells in both tumor and spleen, inhibits tumor growth, and improves animal survival. Moreover, it is demonstrated that this nanovaccine is a general platform of delivering clinically relevant peptide antigens derived from human papilloma virus 16 to trigger antigen-specific immune responses in vivo.

Mitigation of mode instability in laser oscillators based on deuterium loading.

Ytterbium-doped fiber (YDF) loaded with deuterium is used herein to mitigate mode instability. Experimental results reveal that this method can increase the mode instability threshold in a laser oscillator. Specifically, when the YDF was loaded with deuterium over two- and four-week periods, the mode instability threshold power increased from ∼459 W to ∼533 W (16%) and to ∼622 W (35%), respectively, but the respective laser efficiencies were almost unaffected (71.5% vs. 72.9% and 75.4%). In conclusion, deuterium loading is effective in the mitigation of mode instability. It is envisaged to be applied in the power scaling of high-power fiber lasers.