Development of Tumor-Targeted Indocyanine Green-Loaded Ferritin Nanoparticles for Intraoperative Detection of Cancers

Indocyanine green (ICG) is a fluorescent dye with a strong emission in the near-infrared spectral range that allows deep signal penetration and minimal interference of tissue autofluorescence. It has been employed in clinics for different applications, among which the more interesting is certainly near-infrared fluorescence image-guided surgery. This technique has found wide application in surgical oncology for lymph node mapping or for laparoscopic surgery. Despite ICG being useful for tracking loco-regional lymph nodes, it does not provide any information about cancer involvement of such lymph nodes or lymphatic vessels, lacking any tumor-targeting specificity. However, the clinical need in surgical oncology is not only a specific tracking of metastatic nodes but also the intraoperative detection of micrometastatic deposits. Here, we have exploited a nanotechnological solution to improve ICG usefulness by its encapsulation in H-ferritin (HFn) nanocages. They are natural protein-based nanoparticles that exhibit some very interesting features as delivery systems in oncological applications because they display specific tumor homing. We show that HFn loaded with ICG exhibits specific uptake into different cancer cell lines and is able to deliver ICG to the tumor more efficiently than the free dye in an in vivo model of TNBC. Our results pave the way for the application of ICG-loaded HFn in fluorescence image-guided surgery of cancer.