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.
Keywords: ZW800-1; photothermal therapy; renal clearance; tumor targeting; zwitterionic fluorophores.