Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
The People's Hospital of Gaozhou, Maoming 525200, China.
J Mater Chem B. 2023 Oct 25;11(41):10003-10018. doi: 10.1039/d3tb01736b.
Radiotherapy (RT) is dominantly used in breast cancer therapy but is facing fierce side effects because of the limited difference between tumor and normal tissues in response to ionizing radiation. Herein, we construct a core-shell nanoparticle of UiO-66-NH@AuNS. Then the solid gold shell was etched into hollow AuNS (HAuNS) and further modified with biotin-PEG-SH (PEG-bio) to obtain HAuNS@PEG-bio. HAuNS@PEG-bio demonstrates effective near infrared II (NIR-II) region photothermal therapy (PTT) performance, and the increase of temperature at the tumor site promotes the blood circulation to alleviate the hypoxia in the tumor microenvironment (TME). Meanwhile, HAuNS exhibits strong X-ray absorption and deposition ability due to the high atomic coefficient of elemental Au ( = 79) and hollowed-out structure. Through the dual radiosensitization of the high atomic coefficient of Au and the hypoxia alleviation from PTT of HAuNS, the breast cancer cells could undergo immunogenic cell death (ICD) to activate the immune response. At the level, HAuNS@PEG-bio performs NIR-II photothermal, radiosensitization, and ICD therapies through cellular targeting, guided by infrared heat and CT imaging. This work highlights that the constructed biotin-decorated hollow gold nanoshell has a promising potential as a diagnostic and treatment integration reagents for the breast cancer.
放射治疗(RT)在乳腺癌治疗中占主导地位,但由于肿瘤和正常组织对电离辐射的反应有限,因此面临着强烈的副作用。在此,我们构建了 UiO-66-NH@AuNS 的核壳纳米粒子。然后将实心金壳刻蚀成空心 AuNS(HAuNS),并进一步用生物素-PEG-SH(PEG-bio)修饰,得到 HAuNS@PEG-bio。HAuNS@PEG-bio 表现出有效的近红外二区(NIR-II)光热治疗(PTT)性能,肿瘤部位温度的升高促进血液循环,缓解肿瘤微环境(TME)中的缺氧。同时,由于元素金( = 79)的高原子系数和中空结构,HAuNS 表现出很强的 X 射线吸收和沉积能力。通过 HAuNS 的高原子系数的双重放射增敏作用和 PTT 缓解缺氧作用,乳腺癌细胞可以发生免疫原性细胞死亡(ICD),从而激活免疫反应。在体内水平上,HAuNS@PEG-bio 通过细胞靶向,在红外热和 CT 成像的引导下,进行 NIR-II 光热、放射增敏和 ICD 治疗。这项工作强调了构建的生物素修饰的空心金纳米壳作为一种有前途的诊断和治疗一体化试剂,用于乳腺癌。