Multimodal phototheranostics in the short-wavelength infrared range (SWIR, 900-1700 nm) holds significant promise in precision medicine, yet its progress is constrained by photosensitizers that lack effective fluorescence emission due to unwanted intermolecular aggregation and molecularity vibrational patterns. Herein, we present a dual electrostatic anchoring strategy to construct ultrabright co-assembled nanoparticles (NPs) of the squaraine dye SQNMe. This molecular design incorporates two peripheral quaternary ammonium cations: one interacts with the phosphate anion of the liposome mPEG2K-DSPE to achieve intermolecular isolation, while the other forms an internal salt bridge with the central oxycyclobutenolate ring, increasing intramolecular rigidity. Both molecular dynamics simulations and reorganization energy calculations are employed to illustrate the coassembly process. Spectroscopic analysis shows that SQNMe@NPs have a fluorescence brightness of approximately 10135 M-1·cm-1 and a photothermal conversion efficiency of 39.6% in aqueous media. Additionally, the high effectiveness of fluorescence and photoacoustic imaging-guided photothermal therapy for tumors in vivo was successfully demonstrated. These findings highlight the potential of the electrostatic anchoring strategy for improving multimodal tumor phototheranostics.
