Peng Yucheng, Wang Xiaomeng, Wang Yue, Gao Yue, Guo Rui, Shi Xiangyang, Cao Xueyan
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China.
Department of Radiology, Shanghai Songjiang District Central Hospital, Shanghai 201600, China.
Pharmaceutics. 2021 Jun 30;13(7):995. doi: 10.3390/pharmaceutics13070995.
The design of multimodal imaging nanoplatforms with improved tumor accumulation represents a major trend in the current development of precision nanomedicine. To this end, we report herein the preparation of macrophage (MA)-laden gold nanoflowers (NFs) embedded with ultrasmall iron oxide nanoparticles (USIO NPs) for enhanced dual-mode computed tomography (CT) and magnetic resonance (MR) imaging of tumors. In this work, generation 5 poly(amidoamine) (G5 PAMAM) dendrimer-stabilized gold (Au) NPs were conjugated with sodium citrate-stabilized USIO NPs to form hybrid seed particles for the subsequent growth of Au nanoflowers (NFs). Afterwards, the remaining terminal amines of dendrimers were acetylated to form the dendrimer-stabilized FeO/Au NFs (for short, FeO/Au DSNFs). The acquired FeO/Au DSNFs possess an average size around 90 nm, display a high r relaxivity (1.22 mM s), and exhibit good colloidal stability and cytocompatibility. The created hybrid DSNFs can be loaded within MAs without producing any toxicity to the cells. Through the mediation of MAs with a tumor homing and immune evasion property, the FeO/Au DSNFs can be delivered to tumors more efficiently than those without MAs after intravenous injection, thus significantly improving the MR/CT imaging performance of tumors. The developed MA-mediated delivery system may hold great promise for enhanced tumor delivery of other contrast agents or nanomedicines for precision cancer nanomedicine applications.
设计具有改善肿瘤蓄积能力的多模态成像纳米平台是当前精准纳米医学发展的一个主要趋势。为此，我们在此报告制备负载巨噬细胞（MA）的金纳米花（NFs），其嵌入了超小氧化铁纳米颗粒（USIO NPs），用于增强肿瘤的双模态计算机断层扫描（CT）和磁共振（MR）成像。在这项工作中，第5代聚（酰胺胺）（G5 PAMAM）树枝状聚合物稳定的金（Au）纳米颗粒与柠檬酸钠稳定的USIO纳米颗粒共轭，形成混合种子颗粒，用于随后金纳米花（NFs）的生长。之后，树枝状聚合物剩余的末端胺被乙酰化，形成树枝状聚合物稳定的FeO/Au NFs（简称为FeO/Au DSNFs）。所获得的FeO/Au DSNFs平均尺寸约为90 nm，显示出高的r弛豫率（1.22 mM s），并表现出良好的胶体稳定性和细胞相容性。所制备的混合DSNFs可以负载在巨噬细胞内，而不会对细胞产生任何毒性。通过具有肿瘤归巢和免疫逃逸特性的巨噬细胞的介导，静脉注射后，FeO/Au DSNFs比没有巨噬细胞的纳米颗粒能更有效地递送至肿瘤，从而显著提高肿瘤的MR/CT成像性能。所开发的巨噬细胞介导的递送系统对于增强其他造影剂或纳米药物在肿瘤中的递送可能具有巨大潜力，可用于精准癌症纳米医学应用。
