Rational Design of a Self‐Assembling High Performance Organic Nanofluorophore for Intraoperative NIR‐II Image‐Guided Tumor Resection of Oral Cancer

Abstract

The first line of treatment for most solid tumors is surgical resection of the primary tumor with adequate negative margins. Incomplete tumor resections with positive margins account for over 75% of local recurrences and the development of distant metastases. In cases of oral cavity squamous cell carcinoma (OSCC), the rate of successful tumor removal with adequate margins is just 50–75%. Advanced real‐time imaging methods that improve the detection of tumor margins can help improve success rates,overall safety, and reduce the cost. Fluorescence imaging in the second near‐infrared (NIR‐II) window has the potential to revolutionize the field due to its high spatial resolution, low background signal, and deep tissue penetration properties, but NIR‐II dyes with adequate in vivo performance and safety profiles are scarce. A novel NIR‐II fluorophore, XW‐03‐66, with a fluorescence quantum yield (QY) of 6.0% in aqueous media is reported. XW‐03‐66 self‐assembles into nanoparticles (≈80 nm) and has a systemic circulation half‐life (t1/2) of 11.3 h. In mouse models of human papillomavirus (HPV)+ and HPV‐ OSCC, XW‐03‐66 outperformed indocyanine green (ICG), a clinically available NIR dye, and enabled intraoperative NIR‐II image‐guided resection of the tumor and adjacent draining lymph node with negative margins. In vitro and in vivo toxicity assessments revealed minimal safety concerns for in vivo applications.

A dual growth mode unique for organic crystals relies on mesoscopic liquid precursors

“…These behaviors of etioporphyrin I aggregates are consistent with observations of mesoscopic soluterich clusters of proteins 41,[101][102][103] and organic molecules 68,69,104,105 . According to recent models, the mesoscopic clusters form due to accumulation of transient oligomers (Fig.…”

Light‐Responsive Nanoassemblies: Advancing Biomedical Innovation

“…Besides using NIR-responsive nanoassemblies for breast cancer theranostics, its widespread application in cancer treatment stretches out to colorectal, [93,99] ovarian, [100] bladder, [101] oral cancer, etc. [102] Hence, it is anticipated that the integration of diagnostic and therapy properties in a single NIR-responsive nanoassemblies has strong potential in future clinical applications. The capability to run diagnosis and therapy simultaneously with minimal invasiveness can potentially reduce side effects from high drug dosages and treatment costs.…”

Intraoperative Assessment of Resection Margin in Oral Cancer: The Potential Role of Spectroscopy

“…Near-infrared (NIR) fluorescence imaging facilitates real-time margin assessment and guides surgical resection [ 113 , 115 ]. NIR fluorescence imaging has been used successfully in several research studies and clinical procedures for intraoperative image-guided tumor resection, and improved negative margins were observed [ 113 , 116 ].…”