Theranostics 2019; 9(5):1264-1279. doi:10.7150/thno.29101

Research Paper

Theranostic Nanodots with Aggregation-Induced Emission Characteristic for Targeted and Image-Guided Photodynamic Therapy of Hepatocellular Carcinoma

Yang Gao1*, Qi Chang Zheng1*, Shidang Xu2*, Youyong Yuan2, Xiang Cheng1, Shuai Jiang1, Kenry2, Qihong Yu1, Zifang Song1, Bin Liu2✉, Min Li1,3✉

1. Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
2. Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585
3. State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China
*These authors contributed equally to this work.


Photosensitizer (PS) serves as the central element of photodynamic therapy (PDT). The use of common nanoparticles (NPs) for PDT has typically been rendered less effective by the undesirable aggregation-caused quenching (ACQ) effect, resulting in quenched fluorescence and reduced reactive oxygen species (ROS) generation that diminish the imaging quality and PDT efficacy. To overcome the ACQ effect and to enhance the overall efficacy of PDT, herein, integrin ανβ3-targeted organic nanodots for image-guided PDT were designed and synthesized based on a red emissive aggregation-induced emission (AIE) PS.

Methods: The TPETS nanodots were prepared by nano-precipitation method and further conjugated with thiolated cRGD (cRGD-SH) through a click reaction to yield the targeted TPETS nanodots (T-TPETS nanodots). Nanodots were characterized for encapsulation efficiency, conjugation rate, particle size, absorption and emission spectra and ROS production. The targeted fluorescence imaging and antitumor efficacy of T-TPETS nanodot were evaluated both in vitro and in vivo. The mechanism of cell apoptosis induced by T-TPETS nanodot mediated-PDT was explored. The biocompatibility and toxicity of the nanodots was examined using cytotoxicity test, hemolysis assay, blood biochemistry test and histological staining.

Results: The obtained nanodots show bright red fluorescence and highly effective 1O2 generation in aggregate state. Both in vitro and in vivo experiments demonstrate that the nanodots exhibit excellent tumor-targeted imaging performance, which facilitates image-guided PDT for tumor ablation in a hepatocellular carcinoma model. Detailed analysis reveals that the nanodot-mediated PDT is able to induce time- and concentration-dependent cell death. The use of PDT at a high PDT intensity leads to direct cell necrosis, while cell apoptosis via the mitochondria-mediated pathway is achieved under low PDT intensity.

Conclusion: Our results suggest that well-designed AIE nanodots are promising for image-guided PDT applications.

Keywords: aggregation-induced emission (AIE), hepatocellular carcinoma, photodynamic therapy (PDT), integrin ανβ3, theranostics

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How to cite this article:
Gao Y, Zheng QC, Xu S, Yuan Y, Cheng X, Jiang S, Kenry , Yu Q, Song Z, Liu B, Li M. Theranostic Nanodots with Aggregation-Induced Emission Characteristic for Targeted and Image-Guided Photodynamic Therapy of Hepatocellular Carcinoma. Theranostics 2019; 9(5):1264-1279. doi:10.7150/thno.29101. Available from