Rational design of a targeted theranostic nanoagent for sequential application during oral squamous cell carcinoma surgery

Abstract

Oral squamous cell carcinoma (OSCC) is a common cancer of the head and neck, and its treatment outcome depends strongly on whether the tumor is completely removed during surgery. Current tools for preoperative imaging, intraoperative guidance, and postoperative treatment are not well connected, which makes it difficult for surgeons to accurately identify tumor margins and manage residual cancer. Here, we developed a theranostic nanoplatform called AuNPs/HSA–ICG. It is made by loading indocyanine green (ICG) and gold nanoparticles (AuNPs) onto human serum albumin (HSA). This system combines three functions in one: preoperative computed tomography (CT) imaging, intraoperative near-infrared fluorescence guidance, and postoperative photodynamic therapy (PDT). The nanoplatform shows good fluorescence stability, strong CT contrast, and specific tumor-targeting capability attributable to secreted protein acidic and rich in cysteine (SPARC)-mediated active uptake. In an orthotopic tongue cancer model, the combined CT and fluorescence imaging allowed accurate tumor localization and clear visualization of surgical margins, facilitating complete tumor removal. In a residual tumor model simulating positive margins, ICG-based PDT effectively suppressed tumor regrowth. Safety evaluations showed good biocompatibility and low systemic toxicity. Overall, this study presents a clinically translatable, integrated strategy for precise surgical margin management in OSCC, spanning the entire perioperative course.