Synthesis of a Thermal‐Responsive Dual‐Modal Supramolecular Probe for Magnetic Resonance Imaging and Fluorescence Imaging

• Published in: Macromolecular rapid communications. 2021-08, Vol.42 (16), p.e2100248-n/a
• Main Authors: Zhou, Mi, Li, Li, Xie, Wensheng, He, Zejian, Li, Jie
• Format: Article
• Language: English
• Subjects: Acrylamide; Addition polymerization; aggregation‐induced emission; Biocompatibility; Chemical synthesis; Contrast agents; Copolymerization; Copolymers; Cyclodextrin; Cyclodextrins; dual‐modal imaging; Fluorescence; Gadolinium; Gadopentetate dimeglumine; Graft copolymers; Magnetic resonance imaging; Medical imaging; Monomers; MRI; Polymers; Resonance; Supramolecular polymers; temperature response; Toxicity
• ISSN: 1022-1336; 1521-3927
• DOI: 10.1002/marc.202100248

Dual‐modal imaging can integrate the advantages of different imaging technologies, which could improve the accuracy and efficiency of clinical diagnosis. Herein, a novel amphiphilic thermal‐responsive copolymer obtained from three types of monomers, N‐isopropyl acrylamide, 2‐(acetoacetoxy) ethyl methacrylate, and propargyl methacrylate, by RAFT copolymerization, is reported. It can be grafted with β‐cyclodextrin and aggregation‐induced emission (AIE) luminogens tetraphenylethylene by click chemistry and Biginelli reaction. The multifunctional supramolecular polymer (P4) can be constructed by host–guest inclusion between the copolymer and the Gd‐based contrast agent (CA) modified by adamantane [Ad‐(DOTA‐Gd)]. And it can form vesicles with a bilayer structure in aqueous which will enhance the AIE and magnetic resonance imaging effects. As fluorescent thermometer, P4 can enter HeLa cells for intracellular fluorescence imaging (FI) and is sensitive to temperature with detection limit value of 1.5 °C. As magnetic resonance CA, P4 exhibits higher relaxation compared to Magnevist, which can prolong the circulation time in vivo. In addition, Gd3+ in the polymer can be quickly released from the body by disassembly that reduced the biological toxicity. This work introduces new synthetic ideas for dual‐modal probe, which has great potential for clinical diagnostic applications in bioimaging. Vesicles formed by self‐assembly are thermally responsive and can be used as a fluorescent probe and magnetic resonance contrast agent (CA) when they are chelated with Gd3+. In particular, Gd3+ can be quickly removed by disassembly, which effectively reduces harmful effects on the human body.