NIR-II aza-BODIPY Platform for the Development of a Fluorescent Antibody Drug Conjugate

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Abstract
Real-time imaging of antibody-drug conjugates (ADCs) offers valuable insights for assessing tumor targeting specificity, monitoring therapeutic efficacy, and detecting off-target accumulation that may cause adverse effects. To enable precise tracking, we developed a versatile fluorescent platform based on an NIR-II emitting aza-BODIPY dye, which can be site-specifically grafted onto an IgG1 antibody to generate well-defined fluorescent ADCs. As a proof of concept, we synthesized an HER2-targeting trastuzumab immunoconjugate bearing a NIR-II aza-BODIPY fluorophore. The cytotoxic monomethyl auristatin E (MMAE) payload was introduced in the final step, resulting in a trackable and homogeneous ADC suitable for both in vitro and in vivo investigations. The resulting Trastu-azaNIRII-MMAE selectively accumulated in HER2-positive subcutaneous tumors, significantly reducing the tumor growth. Using NIR-II optical imaging, a single injection of the NIR-II-ADC allowed for the detection of the conjugate over a period of more than one month, highlighting its potential for long-term tracking and therapeutic applications.
Funding Information
  • Agence Nationale de la Recherche (ANR-10-EQPX-05-01, ANR-18-CE18-0012)
  • Ligue Contre le Cancer
  • Centre National de la Recherche Scientifique
  • Minist?re de l'Enseignement Sup?rieur et de la Recherche
  • Conseil r?gional de Bourgogne-Franche-Comt?
  • Comit? de C?te d?Or and Comit? de l?Is?re

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