Theranostic Nanoparticles with Aggregation-Induced Emission and MRI Contrast Enhancement Characteristics as a Dual-Modal Imaging Platform for Image-Guided Tumor Photodynamic Therapy

Abstract

Huikang Yang,1,* Yufang He,1,* Yan Wang,2,* Ruimeng Yang,1 Nianhua Wang,1 Li-Ming Zhang,3,* Meng Gao,4 Xinqing Jiang1 1Department of Radiology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province 510640, People’s Republic of China; 2Department of Urology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province 510640, People’s Republic of China; 3School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, Guangdong Province 510275, People’s Republic of China; 4National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong Province 510006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinqing JiangDepartment of Radiology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Yuexiu District, Guangzhou, Guangdong Province 510640, People’s Republic of ChinaTel/Fax [phone]Email [email protected] GaoNational Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Tianhe District, Guangzhou, Guangdong Province 510006, People’s Republic of ChinaTel/Fax [phone]Email [email protected]: Advanced tumor-targeted theranostic nanoparticles play a key role in tumor diagnosis and treatment research. In this study, we developed a multifunctional theranostic platform based on an amphiphilic hyaluronan/poly-(N-ϵ-carbobenzyloxy-L-lysine) derivative (HA-g-PZLL), superparamagnetic iron oxide (SPIO) and aggregation-induced emission (AIE) nanoparticles for tumor-targeted magnetic resonance (MR) and fluorescence (FL) dual-modal image-guided photodynamic therapy (PDT).Materials and Methods: The amphiphilic hyaluronan acid (HA) derivative HA-g-PZLL was synthesized by grafting hydrophobic poly-(N-ϵ-carbobenzyloxy-L-lysine) (PZLL) blocks onto hyaluronic acid by a click conjugation reaction. The obtained HA-g-PZLLs self-assembled into nanoparticles in the presence of AIE molecules and SPIO nanoparticles to produce tumor-targeted theranostic nanoparticles (SPIO/AIE@HA-g-PZLLs) with MR/FL dual-modal imaging ability. Cellular uptake of the theranostic nanoparticles was traced by confocal laser scanning microscopy (CLSM), flow cytometry and Prussian blue staining. The intracellular reactive oxygen species (ROS) generation characteristics of the theranostic nanoparticles were evaluated with CLSM and flow cytometry. The effect of PDT was evaluated by cytotoxicity assay. The dual-mode imaging ability of the nanoparticles was evaluated by a real-time near-infrared fluorescence imaging system and magnetic resonance imaging scanning.Results: The resulting theranostic nanoparticles not only emit red fluorescence for high-quality intracellular tracing but also effectively produce singlet oxygen for photodynamic tumor therapy. In vitro cytotoxicity experiments showed that these theranostic nanoparticles can be efficiently taken up and are mainly present in the cytoplasm of HepG2 cells. After internalization, these theranostic nanoparticles showed serious cytotoxicity to the growth of HepG2 cells after white light irradiation.Discussion: This work provides a simple method for the preparation of theranostic nanoparticles with AIE characteristics and MR contrast enhancement, and serves as a dual-modal imaging platform for image-guided tumor PDT.Keywords: aggregation-induced emission, MR imaging, dual-modal imaging, photodynamic therapy

Keywords

• aggregation induced emission
• mr imaging
• dual-modal imaging
• photodynamic therapy