Mast cells (MCs), powerful immune cells that heavily infiltrate cancer cells, play a crucial role in tumor formation. Activated MCs can release histamine and a family of proteases through degranulation effects, concurrently achieving endothelial junction weakening and stromal degradation of the tumor microenvironment, thereby clearing the obstacles for nano-drug infiltration. To achieve precise activation of tumor-infiltrating MCs, orthogonally excited rare earth nanoparticles (ORENP), with two channels, are introduced for the controllable stimulating drugs release wrapped in "photocut tape". The ORENP can emit near-infrared II (NIR-II) for image tracing for tumor localization in Channel 1 (808/NIR-II) and allows energy upconversion to emit ultraviolet (UV) light for releasing drugs for MCs stimulation in Channel 2 (980/UV). Finally, the combined use of chemical and cellular tools enables clinical nano-drugs to achieve a significant increase in tumor infiltration, thereby enhancing the efficacy of nano-chemotherapy.
Keywords: NIR-II-guided treatment; enhanced nano-chemotherapy; orthogonal light activation; rare-earth nanoparticles; tumor-infiltrating mast cells.
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