Human Serum Albumin Decorated Indocyanine Green Improves Fluorescence-Guided Resection of Residual Lesions of Breast Cancer in Mice

Abstract

ObjectiveAchieving negative resection margin is critical but challenging in breast-conserving surgery. Fluorescence-guided surgery allows the surgeon to visualize the tumor bed in real-time and to facilitate complete resection. We envisioned that intraoperative real-time fluorescence imaging with a human serum albumin decorated indocyanine green probe could enable complete surgical removal of breast cancer in a mouse model.MethodsWe prepared the probe by conjugating indocyanine green (ICG) with human serum albumin (HSA). In vitro uptake of the HSA-ICG probe was compared between human breast cancer cell line MDA-MB-231 and normal breast epithelial cell line MCF 10A. In vivo probe selectivity for tumors was examined in nude mice bearing MDA-MB-231-luc xenografts and the FVB/N-Tg (MMTV-PyMT) 634Mul/J mice model with spontaneous breast cancer. A positive-margin resection mice model bearing MDA-MB-231-luc xenograft was established and the performance of the probe in assisting surgical resection of residual lesions was examined.ResultsA significantly stronger fluorescence intensity was detected in MDA-MB-231 cells than MCF 10A cells incubated with HSA-ICG. In vivo fluorescence imaging showed that HSA-ICG had an obvious accumulation at tumor site at 24 h with tumor-to-normal tissue ratio of 8.19 ± 1.30. The same was true in the transgenic mice model. The fluorescence intensity of cancer tissues was higher than that of non-cancer tissues (58.53 ± 18.15 vs 32.88 ± 11.34). During the surgical scenarios, the residual tumors on the surgical bed were invisible with the naked eye, but were detected and resected with negative margin under HSA-ICG guidance in all the mice (8/8). Recurrence rate among mice that underwent resection with HSA-ICG (0/8) was significantly lower than the rates among mice with ICG (4/8), as well as the control group under white light (7/7).ConclusionsThis study suggests that real-time in vivo visualization of breast cancer with an HSA-ICG fluorescent probe facilitates complete surgical resection of breast cancer in a mouse xenograft model.

Glutathione-Exhausting Nanoprobes for NIR-II Fluorescence Imaging-Guided Surgery and Boosting Radiation Therapy Efficacy via Ferroptosis in Breast Cancer

“…We have always been exploring strategies to visualize the tumor margins when conducting BCS. Human Serum Albumin-ICG (HSA-ICG) was applied to guide surgical resection, and the signal on the surgical bed could be used to guide surgery while the tumor-to-noise ratio was low (approximately 2.5) . On the other hand, R&HV–Gd allowed complete tumor excision under NIR-II fluorescent imaging guiding by reducing aqueous instability and improving target specificity of ICG, but the biosafety of rare-earth-based nanoprobes merited attention .…”

“…Human Serum Albumin-ICG (HSA-ICG) was applied to guide surgical resection, and the signal on the surgical bed could be used to guide surgery while the tumor-to-noise ratio was low (approximately 2.5). 58 On the other hand, R&HV−Gd allowed complete tumor excision under NIR-II fluorescent imaging guiding by reducing aqueous instability and improving target specificity of ICG, but the biosafety of rare-earth-based nanoprobes merited attention. 21 Most recently, our group developed a self-assembled multifunctional nanoprobe Gd DTPA-HSA@ICG-Bevacizumab to improve the efficacy of NIR-II fluorescence image-guided breast cancer surgery, but the photobleaching of ICG is a hurdle to overcome.…”

Indocyanine Green Imaging in Laparoscopic Cholecystectomy Plus Laparoscopic Common Bile Duct Exploration: A Suitable Option for Patients With Difficult Exploration (With Videos)

“…It was introduced in clinical practice early to evaluate liver function and cardiac output and for retinal angiography. 11,12 ICG is metabolized in vivo by liver microsomes and is excreted by the liver into the bile ducts. This property makes it suitable for use as a cholangiocontrast agent.…”

“…ICG is a nontoxic dye that exhibits fluorescent properties when excited by light at near-infrared wavelengths (700 to 900 nm). It was introduced in clinical practice early to evaluate liver function and cardiac output and for retinal angiography 11,12. ICG is metabolized in vivo by liver microsomes and is excreted by the liver into the bile ducts.…”

Radionuclide 131I-labeled albumin-indocyanine green nanoparticles for synergistic combined radio-photothermal therapy of anaplastic thyroid cancer

“…HSA-ICG NPs could stay in the tumor site for a long time. Through fluorescence imaging and photoacoustic imaging, it was helpful to guide the surgical resection of the tumor and the photothermal treatment of the tumor cells ( 43 , 44 ). However, PTT with ICG-HSA had some drawbacks: unnecessary damage to normal tissues led by overheating ( 45 ), lower temperature in deep tumors due to limited laser penetration ( 46 ), limited dosage of HSA to prevent blood pressure drop and immune response ( 47 ), and increased quenching ability of ICG when binding with more HSA ( 47 ).…”