Abstract
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.
Highlights
Near-infrared (NIR) fluorophores have great potential in biomedical applications for image-guided cancer surgery and photothermal therapy (PTT), with distinct advantages, including reduced tissue autofluorescence, targeted tumor imaging, and high photothermal conversion capabilities [1,2,3,4,5]
We developed a renal-clearable PTT agent, Isoniazid to the ZW800-1 NIR Fluorophore (INH–ZW), by conjugating the zwitterionic NIR fluorophore ZW800-1 with the antibiotic drug INH to improve the in vivo performance and fluorescence-guided photothermal cancer therapy
The zwitterionic NIR fluorophore ZW800-1 was designed by Choi et al to have a balanced net surface charge, resulting in ultralow nonspecific uptake and rapid renal clearance [15]
Summary
Near-infrared (NIR) fluorophores have great potential in biomedical applications for image-guided cancer surgery and photothermal therapy (PTT), with distinct advantages, including reduced tissue autofluorescence, targeted tumor imaging, and high photothermal conversion capabilities [1,2,3,4,5]. The efficiency of tumor targeting still remains challenging because the targetability of ligands can be altered by the physicochemical properties of fluorophores after conjugation [8] Among these conjugatable fluorophores, the zwitterionic NIR fluorophore. The MHI-148 and INH conjugate showed significant antitumor efficacy, there is a fundamental limitation of such NIR fluorophores, namely, persistent nonspecific binding, uptake, and retention in normal organs, including the heart, lungs, liver, spleen, and kidneys [18,19]. We developed a renal-clearable PTT agent, INH–ZW, by conjugating the zwitterionic NIR fluorophore ZW800-1 with the antibiotic drug INH to improve the in vivo performance and fluorescence-guided photothermal cancer therapy. The INH–ZW conjugate preserved the ideal biodistribution of ZW800-1 and compensated for tumor targetability, thereby acting as a bifunctional phototherapeutic agent
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