Related Experiment Video
Updated: Aug 7, 2026
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
Clinically accessible drug-based nano-assemblies with self-targeting ability for NIR-II fluorescence imaging-guided
Ruiqin Yang1, Kangliang Lou2, Shuangyan Bao3
1Department of Breast Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China.
Rationale:
Accurate intraoperative visualization is critical for reducing margin positivity during breast-conserving surgery for triple-negative breast cancer (TNBC). Second near-infrared (NIR-II) fluorescence imaging represents a promising approach for precision surgery by combining lesion detection with real-time guidance. Nevertheless, the clinical translation of most fluorescence agents remains hampered by carrier-related toxicity and complex synthesis. Therefore, a "green" drug-repurposing strategy was adopted here to construct carrier-free pure-drug nano-assemblies (PDNAs), aiming to provide a biocompatible and precise intraoperative navigation tool for TNBC resection.
Methods:
We developed a novel PDNA system (CF-ICG) formed by the simple self-assembly of two clinically employed drugs: calcium folinate and indocyanine green. The targeting specificity of CF-ICG and the feasibility of NIR-II fluorescence-guided surgery were validated using MDA-MB-231-Luc xenograft and MMTV-PyVT transgenic models. A rapid ex vivo incubation protocol was developed to differentiate breast cancer from para-cancer tissues.
Results:
Driven by intrinsic Ca2+ from CF, CF-ICG was assembled through π-π stacking and electrostatic interactions, demonstrating stable physicochemical properties and FRα self-targeting ability. In vivo imaging provided high-contrast NIR-II signals for real-time surgical navigation and enabled precise identification of residual submillimeter tumor lesions (diameter ~0.9 mm) in MDA-MB-231-Luc xenograft models. It also clearly differentiated malignant from normal breast tissues in MMTV-PyVT transgenic mice (AUC = 0.941). Furthermore, the diagnostic performance of the rapid ex vivo incubation protocol was preliminarily validated using surgical specimens from TNBC patients (n = 11). Notably, this approach effectively differentiated tumors from para-cancer tissues within 12 min (AUC = 0.926).
Conclusions:
By combining a "green" fabrication process with a drug-repurposing strategy, we developed CF-ICG as a carrier-free PDNA with tumor self-targeting capability, enabling precise intraoperative navigation in preclinical models and ex vivo tissues. These findings support the further development of this approach for more accurate tumor visualization and surgical decision-making in TNBC.
Insights
This study developed a novel, carrier-free nano-assembly (CF-ICG) from existing drugs for precise intraoperative navigation in triple-negative breast cancer (TNBC) surgery. The CF-ICG system enables accurate tumor visualization and margin assessment, improving surgical outcomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Accurate intraoperative visualization is crucial for reducing positive margins in breast-conserving surgery for triple-negative breast cancer (TNBC).
- Second near-infrared (NIR-II) fluorescence imaging offers potential for precision surgery, but clinical translation is limited by carrier toxicity and complex synthesis of agents.
- A green, drug-repurposing strategy is needed to develop biocompatible and precise intraoperative navigation tools for TNBC resection.
Purpose of the Study:
- To develop a carrier-free pure-drug nano-assembly (PDNA) for biocompatible and precise intraoperative navigation in TNBC surgery.
- To evaluate the efficacy of the developed PDNA system (CF-ICG) in targeting specificity and NIR-II fluorescence-guided surgery.
- To establish a rapid ex vivo incubation protocol for differentiating breast cancer from para-cancer tissues.
Main Methods:
- A novel PDNA system, CF-ICG, was created by self-assembling calcium folinate and indocyanine green.
- Targeting specificity and NIR-II fluorescence-guided surgery feasibility were validated in MDA-MB-231-Luc xenograft and MMTV-PyVT transgenic models.
- A rapid ex vivo incubation protocol was developed and validated for differentiating cancerous from normal tissues.
Main Results:
- CF-ICG demonstrated stable physicochemical properties and FRα self-targeting ability, assembled via π-π stacking and electrostatic interactions.
- In vivo imaging revealed high-contrast NIR-II signals for real-time surgical navigation, identifying submillimeter tumor lesions (~0.9 mm).
- The system effectively differentiated malignant from normal breast tissues (AUC = 0.941) and tumors from para-cancer tissues within 12 min (AUC = 0.926) in patient samples.
Conclusions:
- CF-ICG, a carrier-free PDNA with tumor self-targeting capability, was successfully developed using a green fabrication process and drug repurposing.
- This approach enables precise intraoperative navigation in preclinical models and ex vivo tissues, supporting accurate tumor visualization and surgical decision-making in TNBC.
- The findings suggest CF-ICG as a promising tool for enhancing surgical accuracy and patient outcomes in TNBC treatment.
