Polymeric dual-modal imaging nanoprobe with two-photon aggregation-induced emission for fluorescence imaging and gadolinium-chelation for magnetic resonance imaging

• Published in: Bioactive materials 2023-01, Vol.19, p.538-549
• Main Authors: Xiao, Xueyang, Cai, Hao, Huang, Qiaorong, Wang, Bing, Wang, Xiaoming, Luo, Qiang, Li, Yinggang, Zhang, Hu, Gong, Qiyong, Ma, Xuelei, Gu, Zhongwei, Luo, Kui
• Format: Article
• Language: English
• Subjects: Amphiphilic block polymers; Magnetic resonance/fluorescence dual-modal imaging; RAFT polymerization; Tumor/vascular imaging; Two-photon AIE fluorescent contrast agent
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2022.04.026

Nanoprobes that offer both fluorescence imaging (FI) and magnetic resonance imaging (MRI) can provide supplementary information and hold synergistic advantages. However, synthesis of such dual-modality imaging probes that simultaneously exhibit tunability of functional groups, high stability, great biocompatibility and desired dual-modality imaging results remains challenging. In this study, we used an amphiphilic block polymer from (ethylene glycol) methyl ether methacrylate (OEGMA) and N-(2-hydroxypropyl) methacrylamide (HPMA) derivatives as a carrier to conjugate a MR contrast agent, Gd-DOTA, and a two-photon fluorophore with an aggregation-induced emission (AIE) effect, TPBP, to construct a MR/two-photon fluorescence dual-modality contrast agent, Gd-DOTA-TPBP. Incorporation of gadolinium in the hydrophilic chain segment of the OEGMA-based carrier resulted in a high r1 value for Gd-DOTA-TPBP, revealing a great MR imaging resolution. The contrast agent specifically accumulated in the tumor region, allowing a long enhancement duration for vascular and tumor contrast-enhanced MR imaging. Meanwhile, coupling TPBP with AIE properties to the hydrophobic chain segment of the carrier not only improved its water solubility and reduced its cytotoxicity, but also significantly enhanced its imaging performance in an aqueous phase. Gd-DOTA-TPBP was also demonstrated to act as an excellent fluorescence probe for two-photon-excited bioimaging with higher resolution and greater sensitivity than MRI. Since high-resolution, complementary MRI/FI dual-modal images were acquired at both cellular and tissue levels in tumor-bearing mice after application of Gd-DOTA-TPBP, it has great potential in the early phase of disease diagnosis. A highly stable amphiphilic polymer-based magnetic resonance/two-photon AIE fluorescent dual-modality imaging probe Gd-DOTA-TPBP is prepared by RAFT polymerization and copper-free click chemistry. The contrast agent has good biosafety and excellent contrast agent performance. The magnetic resonance/fluorescence dual-modality imaging allows Gd-DOTA-TPBP to acquire complementary information at the tissue and cellular levels in vivo. Therefore, Gd-DOTA-TPBP could be a good candidate for multimodal imaging contrast agents in biomedical applications. [Display omitted] •A highly stable and biocompatibility MR/two-photon AIE fluorescent dual-modality imaging probe Gd-DOTA-TPBP is prepared.•Gd-DOTA and TPBP are conjugated to the hydrophilic and hydrophob