Novel Self-Assembled Multifunctional Nanoprobes for Second-Near-Infrared-Fluorescence-Image-Guided Breast Cancer Surgery and Enhanced Radiotherapy Efficacy

新型自组装多功能纳米探针用于二次近红外荧光图像引导乳腺癌手术和增强放射治疗效果

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作者:Yong-Qu Zhang, Wan-Ling Liu, Xiang-Jie Luo, Jun-Peng Shi, Yun-Zhu Zeng, Wei-Ling Chen, Wen-He Huang, Yuan-Yuan Zhu, Wen-Liang Gao, Rong-Hui Li, Zi-He Ming, Li-Xin Zhang, Rui-Qin Yang, Jia-Zheng Wang, Guo-Jun Zhang

Abstract

Breast-conserving surgery (BCS) is the predominant treatment approach for initial breast cancer. However, due to a lack of effective methods evaluating BCS margins, local recurrence caused by positive margins remains an issue. Accordingly, radiation therapy (RT) is a common modality in patients with advanced breast cancer. However, while RT also protects normal tissue and enhances tumor bed doses to improve therapeutic effects, current radiosensitizers cannot meet these urgent clinical needs. To address this, a novel self-assembled multifunctional nanoprobe (NP) gadolinium (Gd)-diethylenetriaminepentaacetic acid-human serum albumin (HSA)@indocyanine green-Bevacizumab (NPs-Bev) is synthesized to improve the efficacy of fluorescence-image-guided BCS and RT. Fluorescence image guidance of the second near infrared NP improves complete resection in tumor-bearing mice and accurately discriminates between benign and malignant mammary tissue in transgenic mice. Moreover, targeting tumors with NPs induces more reactive oxygen species under X-ray radiation therapy, which not only increases RT sensitivity, but also reduces tumor progression in mice. Interestingly, self-assembled NPs-Bev using HSA, the magnetic resonance contrast agent and Bevacizumab-targeting vascular growth factor A, which are clinically safe reagents, are safe in vitro and in vivo. Therefore, the novel self-assembled NPs provide a solid precision therapy platform to treat breast cancer.

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