Dye-doped fluorescent polypyrrole nanotherapeutic probe as a versatile platform for ratiometric pH-sensing-guided and self-monitored photothermal therapy of tumors

A multifunctional fluorescent polypyrrole nanotherapeutic probe (denoted as PPy@RhB-PAA-FITC) was constructed for pH-sensing-guided photothermal therapy (PTT) of cancer and self-monitoring temperature variations during PTT. Temperature-responsive rhodamine B (RhB) and pH-sensitive fluorescein isothiocyanate (FITC) fluorescent dyes were linked to polypyrrole (PPy) nanoparticles, which served as the photothermal therapy material matrix, through encapsulation and electrostatic interaction, respectively. The fluorescence intensity of FITC increased dramatically with increasing pH, while little variation was observed in the emission intensity of RhB, enabling ratiometric fluorescent pH sensing performance. For pH detection, the nanoprobes exhibited linearity in the pH range from 4.54 to 6.4, with an acid dissociation constant (p<i>K</i>_a) of 5.80. The PPy nanoparticles were responsible for PTT and endowed this nanotherapeutic system with 36.24% photothermal conversion efficiency. Meanwhile, the fluorescence intensity of RhB decreased with an increase in heat-induced temperature, thus enabling self-monitoring of temperature during PTT. A thermal sensitivity of 1.4% °C^-1 was observed for the probe in temperature-sensing assays. Moreover, due to the combination of ratiometric fluorescent pH imaging, photothermal conversion and self-detection of temperature, PPy@RhB-PAA-FITC was successfully applied for pH-mediated tumor diagnosis and could self-monitor the treatment process. The proposed PPy@RhB-PAA-FITC broadens the application of PPy-based nanomaterials in ratiometric fluorescent pH imaging and self-feedback temperature-change-guided photothermal therapy.