Efficacy of indocyanine green-loaded hyaluronic acid nanoparticles for the surgical resection of orthotopic breast tumors

摘要

Breast cancer patients that experience complete removal of the primary tumor, or negative surgical margins (NSMs),benefit from decreased rates of local recurrence and increased survival. However, intraoperative margin detection islimited to visualization, palpation, and experience to identify malignant vs. healthy tissue. As a result, roughly 1/3 ofpatients treated with breast conserving surgery (BCS) have residual cancer cells left at the resection border, or positivesurgical margins (PSMs). Fluorescence image-guided surgery (FIGS) is a promising alternative for intraoperative margindetection, providing surgeons with real-time feedback on tumor location, increasing the likelihood of achieving NSMs.Our past work has demonstrated that the use of self-assembled hyaluronic acid (HA) nanoparticles improves the deliveryof indocyanine green (ICG) to breast tumors, enhancing intraoperative tumor signal and contrast. This study built uponthese findings by assessing the surgical efficacy of ICG-loaded HA nanoparticles (NanoICG) for the image-guidedresection of orthotopic iRFP+/luciferase+ 4T1 breast tumors in BALB/c mice. Tumors were resected with FIGS in micetreated with ICG or NanoICG and compared to bright light surgery (BLS) or sham controls. Tumor growth andrecurrence were monitored with bioluminescence imaging. NanoICG improved complete resection and prolonged tumorfreesurvival. Additionally, NanoICG provided greater intraoperative contrast in malignant tissue than ICG or BLS.Furthermore, NanoICG demonstrated a greater ability to identify small, occult lesions than ICG. Overall, the use ofNanoICG for the fluorescence image-guided resection of breast tumors could potentially decrease PSM rates andimprove complete tumor removal.