Cancer Center and Department of Breast and Thyroid Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361100, China.
Key Laboratory for Endocrine-Related Cancer Precision Medicine of Xiamen, Xiang'an Hospital of Xiamen University, Xiamen, Fujian, 361100, China.
Adv Sci (Weinh). 2022 Apr;9(12):e2104728. doi: 10.1002/advs.202104728. Epub 2022 Feb 16.
Positive resection margin frequently exists in breast-conserving treatment (BCT) of early-stage breast cancer, and insufficient therapeutic efficacy is common during radiotherapy (RT) in advanced breast cancer patients. Moreover, a multimodal nanotherapy platform is urgently required for precision cancer medicine. Therefore, a biodegradable cyclic RGD pentapeptide/hollow virus-like gadolinium (Gd)-based indocyanine green (R&HV-Gd@ICG) nanoprobe is developed to improve fluorescence image-guided surgery and breast cancer RT efficacy. R&HV-Gd exhibits remarkably improved aqueous stability, tumor retention, and target specificity of ICG, and achieves outstanding magnetic resonance/second near-infrared (NIR-II) window multimodal imaging in vivo. The nanoprobe-based NIR-II fluorescence image guidance facilitates complete tumor resection, improves the overall mouse survival rate, and effectively discriminates between benign and malignant breast tissues in spontaneous breast cancer transgenic mice (area under the curve = 0.978; 95% confidence interval: 0.952, 1.0). Moreover, introducing the nanoprobe to tumors generated more reactive oxygen species under X-ray irradiation, improved RT sensitivity, and reduced mouse tumor progression. Notably, the nanoprobe is biodegradable in vivo and exhibits accelerated bodily clearance, which is expected to reduce the potential long-term inorganic nanoparticle toxicity. Overall, the nanoprobe provides a basis for developing precision breast cancer treatment strategies.
保乳治疗（BCT）早期乳腺癌常存在阳性切缘，晚期乳腺癌患者放疗（RT）疗效往往不足。此外，精准癌症医学迫切需要一种多模式纳米治疗平台。因此，开发了一种可生物降解的环状 RGD 五肽/中空病毒样钆（Gd）基吲哚菁绿（R&HV-Gd@ICG）纳米探针，以提高荧光图像引导手术和乳腺癌 RT 疗效。R&HV-Gd 表现出明显提高的水稳定性、肿瘤保留和 ICG 的靶向特异性，并在体内实现了出色的磁共振/近红外二区（NIR-II）窗口多模态成像。基于纳米探针的 NIR-II 荧光图像引导有助于完全切除肿瘤，提高整体小鼠存活率，并有效区分自发性乳腺癌转基因小鼠的良性和恶性乳腺组织（曲线下面积 = 0.978；95%置信区间：0.952, 1.0）。此外，在 X 射线照射下，将纳米探针引入肿瘤中会产生更多的活性氧，提高 RT 敏感性并减少小鼠肿瘤进展。值得注意的是，纳米探针在体内可生物降解，并表现出加速的体内清除率，有望降低潜在的长期无机纳米颗粒毒性。总体而言，该纳米探针为开发精准乳腺癌治疗策略提供了依据。
