Yang Emmy, Qian Weiping, Cao Zehong, Wang Liya, Bozeman Erica N, Ward Christina, Yang Bin, Selvaraj Periasamy, Lipowska Malgorzata, Wang Y Andrew, Mao Hui, Yang Lily
1. Departments of Surgery, Emory University School of Medicine, Atlanta, GA 30322;
2. Departments of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322.
Theranostics. 2015 Jan 1;5(1):43-61. doi: 10.7150/thno.10350. eCollection 2015.
Understanding the effects of immune responses on targeted delivery of nanoparticles is important for clinical translations of new cancer imaging and therapeutic nanoparticles. In this study, we found that repeated administrations of magnetic iron oxide nanoparticles (IONPs) conjugated with mouse or human derived targeting ligands induced high levels of ligand specific antibody responses in normal and tumor bearing mice while injections of unconjugated mouse ligands were weakly immunogenic and induced a very low level of antibody response in mice. Mice that received intravenous injections of targeted and polyethylene glycol (PEG)-coated IONPs further increased the ligand specific antibody production due to differential uptake of PEG-coated nanoparticles by macrophages and dendritic cells. However, the production of ligand specific antibodies was markedly inhibited following systemic delivery of theranostic nanoparticles carrying a chemotherapy drug, doxorubicin. Targeted imaging and histological analysis revealed that lack of the ligand specific antibodies led to an increase in intratumoral delivery of targeted nanoparticles. Results of this study support the potential of further development of targeted theranostic nanoparticles for the treatment of human cancers.
了解免疫反应对纳米颗粒靶向递送的影响对于新型癌症成像和治疗性纳米颗粒的临床转化至关重要。在本研究中，我们发现，重复给予与小鼠或人源靶向配体偶联的磁性氧化铁纳米颗粒（IONP）会在正常小鼠和荷瘤小鼠中诱导高水平的配体特异性抗体反应，而注射未偶联的小鼠配体免疫原性较弱，在小鼠中诱导的抗体反应水平非常低。接受静脉注射靶向且聚乙二醇（PEG）包被的IONP的小鼠，由于巨噬细胞和树突状细胞对PEG包被纳米颗粒的不同摄取，进一步增加了配体特异性抗体的产生。然而，携带化疗药物阿霉素的治疗诊断纳米颗粒全身递送后，配体特异性抗体的产生受到明显抑制。靶向成像和组织学分析表明，缺乏配体特异性抗体导致靶向纳米颗粒在肿瘤内的递送增加。本研究结果支持进一步开发靶向治疗诊断纳米颗粒用于治疗人类癌症的潜力。
