Biodegradable ICG-Conjugated\nGermanium Nanoparticles\nfor <i>In Vivo</i> Near-Infrared Dual-Modality Imaging and\nPhotothermal Therapy

Theranostics, by integrating diagnosis and therapy on\na single\nplatform, enables real-time monitoring of tumors during treatment.\nTo improve the accuracy of tumor diagnosis, the fluorescence and photoacoustic\nimaging modalities can complement each other to achieve high resolution\nand a deep penetration depth. Despite the superior performance, the\nbiodegradability of theranostic agents plays a critical role in enhancing\nnanoparticle excretion and reducing chronic toxicity, which is essential\nfor clinical applications. Herein, we synthesize biocompatible and\nbiodegradable indocyanine green (ICG)-conjugated germanium nanoparticles\n(GeNPs) and investigate their biodistributions in nude mice and 4T1\ntumor models after intravenous injections using near-infrared (NIR)\ndual-modality fluorescence and photoacoustic imaging. The ICG-conjugated\nGeNPs have strong NIR absorption due to the NIR-absorbing ICG and\nGe in combination, emit strong NIR fluorescence due to the multilayered\nICG coatings, and exhibit very low <i>in vitro</i> and <i>in vivo</i> toxicity. After tail vein injections, the ICG-conjugated\nGeNPs mainly accumulate in the liver and spleen as well as the tumor\nwith the help of the enhanced permeability and retention effect. The\ntumor’s fluorescence signal is much stronger than that of the\ncontrol group injected with pure ICG solution, as the GeNPs can function\nas biodegradable carriers for efficiently delivering the ICG molecules\nto the tumor. Lastly, the ICG-conjugated GeNPs accumulated in the\ntumor can also be utilized for photothermal treatment under NIR laser\nirradiation, after which the tumor volume almost diminishes after\n14 days. The experimental findings in this work demonstrate that the\nICG-conjugated GeNPs are promising theranostic agents with exceptional\nbiodegradability for <i>in vivo</i> NIR dual-modality imaging\nand photothermal therapy.