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Updated: Jul 5, 2025

A Bright NIR-II Fluorescence Probe for Vascular and Tumor Imaging
Published on: March 17, 2023
Intratumor injected gold molecular clusters for NIR-II imaging and cancer therapy
Ani Baghdasaryan1, Haoran Liu1, Fuqiang Ren1
1Department of Chemistry and Bio-X, Stanford University, Stanford, CA 94305.
Abstract:
Surgical resections of solid tumors guided by visual inspection of tumor margins have been performed for over a century to treat cancer. Near-infrared (NIR) fluorescence labeling/imaging of tumor in the NIR-I (800 to 900 nm) range with systemically administrated fluorophore/tumor-targeting antibody conjugates have been introduced to improve tumor margin delineation, tumor removal accuracy, and patient survival. Here, we show Au25 molecular clusters functionalized with phosphorylcholine ligands (AuPC, ~2 nm in size) as a preclinical intratumorally injectable agent for NIR-II/SWIR (1,000 to 3,000 nm) fluorescence imaging-guided tumor resection. The AuPC clusters were found to be uniformly distributed in the 4T1 murine breast cancer tumor upon intratumor (i.t.) injection. The phosphocholine coating afforded highly stealth clusters, allowing a high percentage of AuPC to fill the tumor interstitial fluid space homogeneously. Intra-operative surgical navigation guided by imaging of the NIR-II fluorescence of AuPC allowed for complete and non-excessive tumor resection. The AuPC in tumors were also employed as a photothermal therapy (PTT) agent to uniformly heat up and eradicate tumors. Further, we performed in vivo NIR-IIb (1,500 to 1,700 nm) molecular imaging of the treated tumor using a quantum dot-Annexin V (QD-P3-Anx V) conjugate, revealing cancer cell apoptosis following PTT. The therapeutic functionalities of AuPC clusters combined with rapid renal excretion, high biocompatibility, and safety make them promising for clinical translation.
Insights
Gold-based molecular clusters (AuPC) offer precise, image-guided tumor removal and photothermal therapy. This novel agent shows promise for improved cancer treatment and clinical translation due to its safety and efficacy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Traditional cancer surgery relies on visual inspection, often leading to incomplete resection or excessive tissue removal.
- Near-infrared (NIR) fluorescence imaging has improved tumor margin delineation but faces limitations in penetration depth and resolution.
- Advanced imaging agents are needed for more accurate surgical guidance and effective cancer therapy.
Purpose of the Study:
- To evaluate gold-based molecular clusters (AuPC) as an intratumorally injectable agent for NIR-II/SWIR fluorescence imaging-guided tumor resection.
- To assess the therapeutic potential of AuPC for photothermal therapy (PTT) and monitor treatment response using advanced molecular imaging.
Main Methods:
- Synthesis and characterization of Au25 molecular clusters functionalized with phosphorylcholine ligands (AuPC).
- Intratumoral injection of AuPC into 4T1 murine breast cancer models for NIR-II fluorescence imaging.
- Evaluation of AuPC for photothermal therapy (PTT) and subsequent in vivo NIR-IIb imaging of apoptosis using QD-P3-Anx V.
Main Results:
- AuPC demonstrated uniform distribution within tumors after intratumoral injection, facilitated by the stealthy phosphorylcholine coating.
- NIR-II fluorescence imaging of AuPC enabled precise, intra-operative guidance for complete and non-excessive tumor resection.
- AuPC effectively eradicated tumors via PTT, with subsequent NIR-IIb imaging confirming cancer cell apoptosis.
Conclusions:
- AuPC molecular clusters are a promising preclinical agent for image-guided cancer surgery and photothermal therapy.
- The agent's properties, including homogeneous tumor distribution, stealth characteristics, and therapeutic capabilities, support its potential for clinical translation.
- Rapid renal excretion, high biocompatibility, and safety further enhance the clinical prospects of AuPC for cancer treatment.

