Micelle-Encapsulated Theranostic Phthalocyanine and Naphthalocyanine Derivatives for Photothermal Therapy and Photoacoustic Imaging with NIR-I vs NIR-II Irradiation

Phthalocyanines (Pcs) and naphthalocyanines (Ncs) are promising photoactive agents for theranostic applications, particularly in photothermal therapy (PTT) and photoacoustic (PA) imaging. There is strong interest in developing agents with absorbance in the near-infrared (NIR) to exploit increased tissue penetration and higher maximum exposure limits at these wavelengths. This study evaluates Pc and Nc derivatives optimized for the NIR-I (700-980 nm) and NIR-II (980-1700 nm) spectral windows. A series of dyes were synthesized by varying metal centers within two Pc and Nc scaffolds, and their absorption trends were characterized. The dyes were encapsulated in PEG-PCL micelles and assessed for absorption, heating efficiency, and PA imaging with 810 and 980 nm lasers. Using a murine mammary tumor model, CuNc(Octa) and SnNc(Octa) emerged as the most effective NIR-I and NIR-II candidates, respectively. NIR-II phototherapy demonstrated superior tumor ablation due to deeper penetration and higher permissible exposure limits but raised safety concerns from rapid heating of healthy tissue. Our findings suggest that increasing 810 nm laser power above current limits could improve specificity and efficacy while mitigating risks. This study highlights key advantages and challenges of NIR-I and NIR-II irradiation, providing insights for next-generation Pc and Nc theranostic agents.