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Facile Synthesis of Gadolinium Chelate-Conjugated Polymer Nanoparticles for Fluorescence/Magnetic Resonance Dual-Modal Imaging
Analytical Chemistry ( IF 6.7 ) Pub Date : 2018-01-17 00:00:00 , DOI: 10.1021/acs.analchem.7b04078
Yi Pan 1 , Wandi Chen 1 , Jun Yang 2 , Junhui Zheng 2 , Mengsu Yang 3 , Changqing Yi 1
Affiliation  

Fluorescence (FL)/magnetic resonance (MR) dual-modal imaging nanoprobes are significant not only for cutting edge research in molecular imaging, but also for clinical diagnosis with high precision and accuracy. However, synthesis of FL/MR dual-modal imaging nanoprobes that simultaneously exhibit strong fluorescent brightness and high MR response, long-term colloidal stability with uniform sizes, good biocompatibility and a versatile surface functionality has proven challenging. In this study, the well-defined core–shell structured Gd3+ chelate-conjugated fluorescent polymer nanoparticles (Gd-FPNPs) that consist of rhodamine B (RB)-encapsulated poly(methyl methacrylate) (PMMA) cores and Gd3+ chelate-conjugated branched polyethylenimine (PEI) shells, are facilely synthesized via a one-step graft copolymerization of RB-encapsulated MMA from PEI-DTPA-Gd induced by tert-butyl hydroperoxide (TBHP) at 80 °C for 2 h. The mild synthesis route not only preserves the chemical environment for Gd3+ coordination, but also improves optical properties and chemo-/photostability of RB. A high local concentration of outer surface-chelated Gd3+ and their direct interactions with hydrogen protons endow Gd-FPNPs high longitudinal relaxivity (26.86 mM–1 s–1). The uniform spherical structure of Gd-FPNPs facilitates their biotransfer, and their surface carboxyl and amine groups afford them both long-term colloidal stability and cell-membrane permeability. The excellent biocompatibility and FL/MR dual-modal imaging capability of Gd-FPNPs are demonstrated using HeLa cells and mice as models. All the results confirm that Gd-FPNPs fulfill the design criteria for a high-performance imaging nanoprobe. In addition, this study enables such probes to be prepared also by those not skilled in nanomaterial synthesis, and thus promoting the development of novel functional imaging nanoprobes.

中文翻译:

Synthesis /螯合物共轭聚合物纳米粒子的荧光/磁共振双模态成像的简便合成

荧光(FL)/磁共振(MR)双模态成像纳米探针不仅对分子成像的前沿研究具有重要意义,而且对高精度和高精度的临床诊断也具有重要意义。然而,已证明同时显示强荧光亮度和高MR响应,具有统一尺寸的长期胶体稳定性,良好的生物相容性和通用的表面功能的FL / MR双峰成像纳米探针的合成具有挑战性。在这项研究中,由罗丹明B(RB)封装的聚甲基丙烯酸甲酯(PMMA)核和Gd 3+组成的定义明确的核-壳结构Gd 3+螯合物共轭的荧光聚合物纳米粒子(Gd-FPNPs)通过丁基过氧化氢(TBHP)在80°C下诱导的PEI-DTPA-Gd的RB包埋的MMA的一步接枝共聚合,轻松合成了螯合共轭的支链聚乙烯亚胺(PEI)壳。温和的合成路线不仅保留了Gd 3+配位的化学环境,而且还改善了RB的光学性质和化学/光稳定性。外表面螯合的Gd 3+的高局部浓度及其与氢质子的直接相互作用赋予Gd-FPNPs高纵向弛豫性(26.86 mM –1 s –1)。Gd-FPNPs的均匀球形结构促进了它们的生物转移,并且它们的表面羧基和胺基为它们提供了长期的胶体稳定性和细胞膜通透性。Gd-FPNPs的出色的生物相容性和FL / MR双模成像能力已证明使用HeLa细胞和小鼠作为模型。所有结果证实,Gd-FPNPs符合高性能成像纳米探针的设计标准。此外,这项研究还使纳米材料合成领域的技术人员也可以制备此类探针,从而促进了新型功能成像纳米探针的发展。
更新日期:2018-01-17
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