Ji Chao, Zhao Maoru, Wang Chengyan, Liu Ruixue, Zhu Shuang, Dong Xinghua, Su Chunjian, Gu Zhanjun
Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology of China, Chinese Academy of Sciences, Beijing 100049, China.
College of Mechanical and Electronic Engineering, Shandong University of Science and Technology, Qingdao 266590, China.
ACS Nano. 2022 Jun 28;16(6):9428-9441. doi: 10.1021/acsnano.2c02314. Epub 2022 Jun 6.
Metastasis of breast carcinoma is commonly realized through lymphatic circulation, which seriously threatens the lives of breast cancer patients. Therefore, efficient therapy for both primary tumor and metastatic sentinel lymph nodes (SLNs) is highly desired to inhibit cancer growth and metastasis. During breast cancer treatment, radiotherapy (RT) is a common clinical method. However, the efficacy of RT is decreased by the radioresistance to a hypoxic microenvironment and inevitable side effects for healthy issues at high radiation doses. Considering the above-mentioned, we provide high biocompatible poly(vinylpyrrolidone) coated Ta nanoparticles (Ta@PVP NPs) for photothermal therapy (PTT) assisted RT for primary tumor and metastatic SLNs. On the one hand, for primary tumor treatment, Ta@PVP NPs with a high X-ray mass attenuation coefficient (4.30 cm/kg at 100 keV) can deposit high radiation doses within tumors. On the other hand, for metastatic SLNs treatment, the effective delivery of Ta@PVP NPs from the primary tumor into SLNs is monitored by computed tomography and photoacoustic imaging, which greatly benefit the prognosis and treatment for metastatic SLNs. Moreover, Ta@PVP NPs-mediated PTT could enhance the RT effect, and immunogenic cell death caused by RT/PTT could induce an immune response to improve the therapeutic effect of metastatic SLNs. This study not only explores the potential of Ta@PVP NPs as effective radiosensitizers and photothermal agents for combined RT and PTT but also offers an efficient strategy to cure both primary tumor and metastatic SLNs in breast carcinoma.
乳腺癌转移通常通过淋巴循环实现，这严重威胁着乳腺癌患者的生命。因此，人们迫切需要对原发性肿瘤和转移性前哨淋巴结（SLN）进行有效治疗，以抑制癌症生长和转移。在乳腺癌治疗过程中，放射治疗（RT）是一种常见的临床方法。然而，由于对缺氧微环境的放射抗性以及高辐射剂量对健康问题不可避免的副作用，RT的疗效会降低。考虑到上述情况，我们提供了具有高生物相容性的聚乙烯吡咯烷酮包覆钽纳米颗粒（Ta@PVP NPs），用于对原发性肿瘤和转移性SLN进行光热疗法（PTT）辅助RT。一方面，对于原发性肿瘤治疗，具有高X射线质量衰减系数（在100 keV时为4.30 cm/kg）的Ta@PVP NPs可在肿瘤内沉积高辐射剂量。另一方面，对于转移性SLN治疗，通过计算机断层扫描和光声成像监测Ta@PVP NPs从原发性肿瘤到SLN的有效递送，这对转移性SLN的预后和治疗大有裨益。此外，Ta@PVP NPs介导的PTT可增强RT效果，RT/PTT引起的免疫原性细胞死亡可诱导免疫反应，从而提高转移性SLN的治疗效果。本研究不仅探索了Ta@PVP NPs作为联合RT和PTT的有效放射增敏剂和光热剂的潜力，还提供了一种治疗乳腺癌原发性肿瘤和转移性SLN的有效策略。
