Monoclonal Antibody-Based Near-Infrared Cancer Phototheranostics: Emerging Strategies and Translational Perspectives

Abstract Monoclonal Antibody-Based Near-Infrared Cancer Phototheranostics have emerged as a versatile platform for cancer phototheranostics by integrating antigen-specific targeting with spatiotemporally controlled imaging and therapy. Conjugation of monoclonal antibodies (mAb) with NIR-responsive photosensitizers enables selective tumor localization and light-triggered cytotoxicity, thereby minimizing off-target toxicity while enhancing therapeutic precision. Despite promising preclinical outcomes, clinical translation remains constrained by limited intratumoral penetration of macromolecular constructs, heterogeneous antigen expression, and restricted light delivery to deep-seated tumors. Additional challenges, large-scale manufacturing, and regulatory complexity further hinder widespread clinical adoption. This review provides a critical analysis of recent advances in NIR-based antibody phototheranostics, with emphasis on rational design parameters such as antibody selection, photosensitizer engineering, and conjugation strategies. Emerging approaches, including nanocarrier-assisted delivery, tumor microenvironment modulation, and immune checkpoint-directed combination therapies, are discussed in the context of enhancing therapeutic and translational potential. Finally, future directions focusing on activatable and tumor microenvironment-responsive probes, exploration of the NIR-II window, and optimized irradiation strategies are highlighted as key avenues to bridge the gap between preclinical promise and clinical translation.