Fig. 8

Bioluminescence imaging the delivery of Tat/TF-Ca²⁺ nanoparticles promoted by GRP75-driven, cell-cycle-dependent macropinocytosis. (A) In vivo analysis of the targeted delivery of Tat/TF-Ca²⁺ nanoparticles by Rluc imaging. Representative mice from different treatments are shown. (B) Quantitative analysis of mouse BLI signals being shown as photons/sec/cm2/sr. (C) Confirmation of Tat/TF-Ca²⁺ nanoparticles targeted delivery to ovarian cancer by anti-RFP immunohistochemistry, and (D) RFP-expressed signal from tumor tissue was quantified and analyzed. *P < 0.05, **P < 0.01. ns no difference. (E) Schematic illustration of GRP75-driven, cell-cycle-dependent macropinocytosis of Tat/pDNA-Ca²⁺ nanoparticles. Ca²⁺ addition markedly condensed Tat/pDNA nanocomplexes. Uptake of Tat/pDNA/Ca²⁺ nanoparticles was activated in cell-cycle S-phase and controlled by GRP75-driven, cell-cycle-dependent macropinocytosis. GRP75 interacts with Mps1, phosphorylates by Mps1, and forms a feedback-activation loop with MPS1. This signaling drives centrosome duplication, promotes cell-cycle S-phase enriched and M-phase arrested, and induces the macropinocytosis of Tat/TF-Ca²⁺ nanoparticles upregulated in these two sub-phases