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A novel mutation in FBXL4 in a Norwegian child with encephalomyopathic mitochondrial DNA depletion syndrome 13

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To solve the paradox that pre-existing high concentrations of ROS in the TME can conversely inhibit immunity, the most advanced strategy is to develop multifunctional nanovaccines that first clear, then activate. Such vaccines can first use their material properties to scavenge the inhibitory ROS in the TME, creating a favorable environment for immune cells, and then strongly activate DCs by releasing immune agonists, ultimately triggering a systemic anti-tumor immunity [265]

The resulting strategy families correspond to major design objectives: improving pharmacokinetics and biodistribution [33, 37, 53, 66, 67], modulating vascular access and perfusion [11, 12, 15, 68, 69], normalizing or reprogramming stromal barriers [13, 17, 30, 32, 34, 70], enabling endogenous TME-responsive release or activation [46,47,48], reshaping antitumor immunity [29, 35, 71], and integrating imaging with therapeutic intervention [72,73,74]