The combination of near-infrared (NIR) fluorophores and
photothermal therapy (PTT) provides a new opportunity for safe and effective
cancer treatment. However, the precise molecular design of functional NIR fluorophores with desired properties, such as high
tumor targetability and low nonspecific uptake, remains challenging. In this study, a renal-clearable NIR fluorophore conjugate with high
tumor targetability was developed for efficient photothermal
cancer therapy. The
isoniazid (INH)-ZW800-1 conjugate (INH-ZW) was synthesized by conjugating an
antibiotic drug, INH, with a well-known zwitterionic NIR fluorophore, ZW800-1, to improve in vivo performance and fluorescence-guided
cancer phototherapy. INH-ZW not only showed rapid
tumor accumulation without nonspecific tissue/organ uptake within 1 h after the injection but also generated thermal energy to induce
cancer cell death under NIR
laser irradiation. Compared with previously reported ZW800-1 conjugates, INH-ZW preserved the ideal biodistribution of ZW800-1 and facilitated improved
tumor targeting and PTT. Together, these results demonstrate that the INH-ZW conjugate has great potential to serve as an effective PTT agent capable of rapid
tumor targeting and high renal clearance, with excellent photothermal efficacy.