Damasco Jossana A, Ohulchanskyy Tymish Y, Mahajan Supriya, Chen Guanying, Singh Ajay, Kutscher Hilliard L, Huang Haoyuan, Turowski Steven G, Spernyak Joseph A, Singh Anurag K, Lovell Jonathan F, Seshadri Mukund, Prasad Paras N
Department of Chemistry and Institute for Lasers, Photonics and Biophotonics, University At Buffalo, The State University of New York, Buffalo, NY 14260 USA.
Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA.
Cancer Nanotechnol. 2021;12(1):4. doi: 10.1186/s12645-021-00075-x. Epub 2021 Feb 5.
In this study, we report on the synthesis, imaging, and radiosensitizing properties of ultrasmall β-NaGdF:Yb50% nanoparticles as a multifunctional theranostic platform. The synthesized nanoparticles act as potent bimodal contrast agents with superior imaging properties compared to existing agents used for magnetic resonance imaging (MRI) and computed tomography (CT). Clonogenic assays demonstrated that these nanoparticles can act as effective radiosensitizers, provided that the nanoparticles are taken up intracellularly.
Our ultrasmall β-NaGdF:Yb50% nanoparticles demonstrate improvement in T1-weighted contrast over the standard clinical MR imaging agent Gd-DTPA and similar CT signal enhancement capabilities as commercial agent iohexol. A 2 Gy dose of X-ray induced ~ 20% decrease in colony survival when C6 rat glial cells were incubated with non-targeted nanoparticles (NaGdF:Yb50%), whereas the same X-ray dose resulted in a ~ 60% decrease in colony survival with targeted nanoparticles conjugated to folic acid (NaGdF:Yb50%-FA). Intravenous administration of nanoparticles resulted in clearance through urine and feces within a short duration, based on the ex vivo analysis of Gd ions via ICP-MS.
These biocompatible and in vivo clearable ultrasmall NaGdF:Yb50% are promising candidates for further evaluation in image-guided radiotherapy applications.
在本研究中,我们报告了超小β-NaGdF:Yb50%纳米颗粒作为多功能诊疗平台的合成、成像及放射增敏特性。与用于磁共振成像(MRI)和计算机断层扫描(CT)的现有造影剂相比,合成的纳米颗粒作为有效的双模态造影剂,具有卓越的成像特性。克隆形成试验表明,只要纳米颗粒被细胞内摄取,它们就可以作为有效的放射增敏剂。
我们的超小β-NaGdF:Yb50%纳米颗粒在T1加权对比度方面比标准临床MR成像剂钆喷酸葡胺有所改善,并且与商业造影剂碘海醇具有相似的CT信号增强能力。当C6大鼠神经胶质细胞与非靶向纳米颗粒(NaGdF:Yb50%)孵育时,2 Gy剂量的X射线导致集落存活率降低约20%,而相同X射线剂量与叶酸偶联的靶向纳米颗粒(NaGdF:Yb50%-FA)导致集落存活率降低约60%。基于通过电感耦合等离子体质谱(ICP-MS)对钆离子的离体分析,纳米颗粒静脉给药后在短时间内通过尿液和粪便清除。
这些具有生物相容性且可在体内清除的超小NaGdF:Yb50%纳米颗粒有望在图像引导放射治疗应用中进行进一步评估。