Synthesis and Photophysical Characterization of Axially Functionalized Silicon(IV) Naphthalocyanines with Phototheranostic Potential

Pedro M. R., Santos, Benjamin, Proto, Debalina, Mondal, Alicia, Voge, Christine, Hoskin, Hanyi, Weng, Inês R. M., Santos, Kevin, Stamplecoskie, João P. C., Tomé, Juan, Chen, Nahyun, Kwon, Gang, Zheng

ChemistryEurope |

Naphthalocyanines are emerging as highly promising photosensitizers, owing to their intensive absorption ( ε > 1 × 10 5 M −1 cm −1 ) beyond 800 nm, but their poor solubility in biological media has significantly limited their clinical translation. In this study, the synthesis and detailed photophysical characterization of silicon naphthalocyanines (SiNcs) functionalized with structurally diverse axial ligands designed to enhance solubility and evaluate photophysical properties for theranostic applications are reported. Through an efficient synthetic approach, a library of SiNc derivatives are generated and systematically evaluated for their Q‐band absorption shift, absolute fluorescence quantum yields, lifetime, radiative decay rate, and singlet oxygen generation. The lead compound, SiNc 3 , is encapsulated in poly(ethylene glycol)‐b‐poly( ε ‐caprolactone) (PEG‐PCL) micelles to improve biocompatibility and in vivo delivery. Axial ligand modifications are found to influence aggregation behavior within the nanoformulation, enabling SiNc 3‐PP to retain a strong and sharp absorption peak at 810 nm and exhibit high photothermal conversion efficiency (62.1%). SiNc 3‐PP demonstrates strong photoacoustic imaging contrast at 810 nm, and upon near‐infrared irradiation in tumor‐bearing mice, induced rapid tumor heating up to 54 °C within 5 min, resulting in significant tumor growth inhibition. These findings underscore the pivotal role of axial ligand engineering in tuning SiNc behavior and highlight their potential as theranostic agents integrating photoacoustic imaging and photothermal therapy.