Xu Li, Wan Caifeng, Du Jing, Li Hongli, Liu Xuesong, Yang Hong, Li Fenghua
a Department of Ultrasound , Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , PR China.
b The Key Laboratory of Resource Chemistry of Ministry of Education and the Shanghai Key Laboratory of the Rare Earth Functional Materials, Department of Chemistry , College of Life and Environmental Science, Shanghai Normal University , Shanghai , PR China.
J Biomater Sci Polym Ed. 2017 Mar;28(4):415-430. doi: 10.1080/09205063.2016.1277828. Epub 2017 Jan 16.
Breast cancer is the leading cause of cancer-related deaths in women and earlier detection can substantially reduce deaths from breast cancer. Polymers with targeted ligands are widely used in the field of molecular ultrasound imaging and targeted tumor therapy. In our study, the nanotheranostic agent was fabricated through filling perfluoropropane (CF) into poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NPs), followed by the formation of gold nanoshell on the surface, then conjugated with anti p53 antibody which has high specificity with the p53 protein overexpressing in breast cancer. The average diameter of the gold nanoshelled PLGA NPs carrying anti p53 antibody (p53-PLGA@Au NPs) was 247 ± 108.2 nm. The p53-PLGA@Au NPs had well-defined spherical morphology and hollow interiors observed by electron microscope, and had a good photothermal effect under the irradiation of an 808 nm laser. The results of laser scanning confocal microscope (LSCM) and flow cytometer (FCM) indicated the specific targeting of p53-PLGA@Au NPs conjugating with breast cancer MCF-7 cells overexpressing p53 protein in vitro. Also the ultrasound imaging experiments in vitro showed that p53-PLGA@Au NPs were suitable for ultrasound contrast imaging. In conclusion, the p53-PLGA@Au NPs are demonstrated to be novel targeted UCAs and may have potential applications in the early diagnosis and targeted near-infrared (NIR) photothermal therapy of breast cancer in the future.
乳腺癌是女性癌症相关死亡的主要原因，早期检测可大幅降低乳腺癌死亡率。带有靶向配体的聚合物广泛应用于分子超声成像和靶向肿瘤治疗领域。在我们的研究中，通过将全氟丙烷（CF）填充到聚（d，l-乳酸-共-乙醇酸）纳米颗粒（PLGA NPs）中制备纳米诊疗剂，随后在其表面形成金纳米壳，然后与对乳腺癌中过表达的p53蛋白具有高特异性的抗p53抗体偶联。携带抗p53抗体的金纳米壳PLGA NPs（p53-PLGA@Au NPs）的平均直径为247±108.2 nm。通过电子显微镜观察，p53-PLGA@Au NPs具有明确的球形形态和中空内部结构，并且在808 nm激光照射下具有良好的光热效应。激光扫描共聚焦显微镜（LSCM）和流式细胞仪（FCM）的结果表明，p53-PLGA@Au NPs在体外可特异性靶向与过表达p53蛋白的乳腺癌MCF-7细胞结合。体外超声成像实验也表明p53-PLGA@Au NPs适用于超声造影成像。总之，p53-PLGA@Au NPs被证明是新型靶向超声造影剂，未来可能在乳腺癌的早期诊断和靶向近红外（NIR）光热治疗中具有潜在应用。
