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

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.