Doping Bulky Fluorinated Organic Anion to Construct Highly Efficient Anion‐π + Type Photosensitizers for Cancer Phototheranostics

Anion-π⁺ type photosensitizers with aggregation-induced emission (AIE) feature have demonstrated promising potential in photodynamic therapy (PDT) against cancer. However, previous reports mainly focused on modifying the π⁺ core but often overlooked the crucial role of anions. Herein, we present a facile strategy to modulate the fluorescence intensity and cellular uptake of anion-π⁺ type AIE photosensitizers by doping bulky fluorinated organic anions into nanoparticles (NPs). Anion-π⁺ type AIE photosensitizer DPBCF-Br with different ratios of bulky anions (TB or FTB) were encapsulated into DSPE-PEG₂₀₀₀ to obtain NPs (named DF-TB_X or DF-FTB_X, X denotes the molar ratios of TB or FTB to DPBCF-Br). Expectedly, as the doping molar ratios increased, a progressive enhancement in fluorescence intensity of the obtained NPs was observed. This can be ascribed to the steric effect of bulky organic anions and the formation of a hydrophobic environment within the NPs. Interestingly, the optimal cellular uptake was achieved at X = 8 in DF-TB₈ and DF-FTB₈, resulting from the balance between lipophilicity and electronegativity. Ultimately, DF-FTB₈ demonstrated outstanding cellular imaging capabilities and high intracellular reactive oxygen species generation, achieving efficient cancer phototheranostics. This facile bulky anion doping strategy will pave a new way for the construction of robust anion-π⁺ type photosensitizers.