Tumor Targeting with Methotrexate-Conjugated Zwitterionic Near-Infrared Fluorophore for Precise Photothermal Therapy |
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Authors: | Gayoung Jo Eun Jeong Kim Min Ho Park Hoon Hyun |
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Affiliation: | 1.Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun 58128, Republic of Korea;2.Department of Surgery, Chonnam National University Medical School, Hwasun 58128, Republic of Korea;3.BioMedical Sciences Graduate Program (BMSGP), Chonnam National University, Hwasun 58128, Republic of Korea |
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Abstract: | Targeted tumor imaging can effectively enable image-guided surgery and precise cancer therapy. Finding the right combination of anticancer drugs and near-infrared (NIR) fluorophores is the key to targeted photothermal cancer treatment. In this study, a tumor-targetable NIR fluorophore conjugate with rapid body clearance was developed for accurate tumor imaging and effective photothermal therapy (PTT). The methotrexate (MTX) and zwitterionic NIR fluorophore conjugate (MTX-ZW) were prepared by conjugating a folate antagonist MTX with an aminated ZW800-1 analog to increase the tumor targetability for NIR laser-based PTT of cancer. The MTX, known as a poor tumor-selective drug, showed high tumor accumulation and rapid background clearance after conjugation with the highly water-soluble zwitterionic NIR fluorophore up to 4 h post-injection. The photothermal energy was generated from the MTX-ZW conjugate to induce necrotic cell death in the targeted tumor site under 808 nm laser irradiation. Compared with the previously reported MTX conjugates, the MTX-ZW conjugate can be a great candidate for targeted tumor imaging and fluorescence-guided photothermal cancer therapy. Therefore, these results provide a strategy for the design of drug-fluorophore conjugates and elaborate therapeutic platforms for cancer phototherapy. |
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Keywords: | methotrexate zwitterionic fluorophores near-infrared fluorescence imaging photothermal therapy tumor targeting |
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