Abstract: Objective  To investigate the efficiency and mechanism of the reduction-gated pH transition-switchable delivery system (RPS) in tumor imaging. Methods  Reduction-sensitive monomers (HEMA-SS-C3 and AMA-SS-C3) were synthesized, and polymers with different monomer ratios were prepared via atom transfer radical polymerization (ATRP) to construct RPS polymers. The physicochemical properties of polymers and micelles were characterized by using dynamic light scattering (DLS), fluorescence spectroscopy, and nuclear magnetic resonance hydrogen spectroscopy (1H-NMR). Cellular uptake and in vivo tumor imaging effects were evaluated through flow cytometry and living imaging system. Results  The RPS micelles exhibited a particle size of 30-50 nm. After reduction response, the pH transition point increased from approximately 5.5 to 6.5, and in vitro cellular uptake was significantly enhanced. In vivo imaging revealed that RPS micelles exhibited favorable tumor-imaging effects. Conclusion  RPS possesses a reduction-gated pH transition-tunable property, providing a novel design concept and research basis for precise tumor imaging and drug delivery.

Key words: stimuli-responsive delivery system, tumor microenvironment, reduction response, glutathione, ultra-pH-sensitive polymers, tumor imaging