Gold Nanocage-Based Multifunctional Nanosensitizers for Programmed Photothermal /Radiation/Chemical Coordinated Therapy Guided by FL/MR/PA Multimodal Imaging

Abstract

Xinni Pan,1 Yi Lu,2 Shanshan Fan,1 Hao Tang,2 Haisong Tan,3 Cheng Cao,2 Yingsheng Cheng,1 Yanlei Liu2 1Department of Radiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Instrument Science and Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Urology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Yingsheng Cheng, Department of Radiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200235, People’s Republic of China, Tel [phone], Email [email protected] Yanlei Liu, Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People’s Republic of China, Tel [phone], Email [email protected]: Radiotherapy is one of the main clinical methods for the treatment of malignant tumors at present. However, its application is limited by the radiation resistance of some tumor cells and the irradiation damage to the surrounding normal tissues, and the limitation of radiotherapy dose also affects the therapeutic effect. Therefore, developing diagnostic and therapeutic agents with imaging and radiosensitizing functions is urgently needed to improve the accuracy and efficacy of radiotherapy.Materials and Strategy: Herein, we synthesized multifunctional nanotheranostic FRNPs nanoparticles based on gold nanocages (GNCs) and MnO2 for magnetic resonance (MR)/photoacoustic (PA) imaging and combined photothermal, radiosensitive and chemical therapy. A programmed therapy strategy based on FRNPs is proposed. First, photothermal therapy is applied to ablate large tumors and increase the sensitivity of the tumor tissue to radiotherapy, then X-ray radiation is performed to further reduce the tumor size, and finally chemotherapeutic agents are used to eliminate smaller residual tumors and distant metastases.Results: As revealed by fluorescence, MR and PA imaging, FRNPs achieved efficient aggregation and retention at tumor sites of mice after intravenous injection. In vivo studies have shown that the programmed treatment of FRNPs-injected nude mice which were exposed to X-ray after 808 laser irradiation achieved the greatest inhibition of tumor growth compared with other treatment groups. Moreover, no obvious systemic toxicity was observed in all groups of mice, indicating the good biocompatibility of FRNPs and the safety of the treatment scheme.Conclusion: To sum up, our work not only showed a new radiosensitizer, but also provided a promising theranostic strategy for cancer treatment.Keywords: gold nanoparticles, MnO2, radiosensitizing, multimodal imaging, cancer therapy

Keywords

• gold nanoparticles
• mno2
• radiosensitizing
• multimodal imaging
• cancer therapy