International Journal of Nanomedicine (Apr 2024)
Folic Acid Functionalized AQ4N/Gd@PDA Nanoplatform with Real-Time Monitoring of Hypoxia Relief and Enhanced Synergistic Chemo/Photothermal Therapy in Glioma
Abstract
Longjiang Zhou,1,* Haitao Xiang,2,* Susu Liu,3 Honglin Chen,4 Yuanwei Yang,4 Jianyong Zhang,4 Wei Cai4 1Department of Neurology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225012, People’s Republic of China; 2Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, 215028, People’s Republic of China; 3School of Life Science and Technology, Xidian University and Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi’an, 710126, People’s Republic of China; 4Department of Neurosurgery, Suqian First Hospital, Suqian, 223800, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Cai; Jianyong Zhang, Department of Neurosurgery, Suqian First Hospital, No. 120, Suzhi Road, Sucheng District, Suqian, Jiangsu Province, People’s Republic of China, Tel +86 15162908957 ; +86 15261296169, Fax +86 527 80766363 ; +86 527 80766155, Email [email protected]; [email protected]: Hypoxia is often associated with glioma chemoresistance, and alleviating hypoxia is also crucial for improving treatment efficacy. However, although there are already some methods that can improve efficacy by alleviating hypoxia, real-time monitoring that can truly achieve hypoxia relief and efficacy feedback still needs to be explored.Methods: AQ4N/Gd@PDA-FA nanoparticles (AGPF NPs) were synthesized using a one-pot method and were characterized. The effects of AGPF NPs on cell viability, cellular uptake, and apoptosis were investigated using the U87 cell line. Moreover, the effectiveness of AGPF NPs in alleviating hypoxia was explored in tumor-bearing mice through photoacoustic imaging. In addition, the diagnosis and treatment effect of AGPF NPs were evaluated by magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) on orthotopic glioma mice respectively.Results: In vitro experiments showed that AGPF NPs had good dispersion, stability, and controlled release. AGPF NPs were internalized by cells through endocytosis, and could significantly reduce the survival rate of U87 cells and increase apoptosis under irradiation. In addition, we monitored blood oxygen saturation at the tumor site in real-time through photoacoustic imaging (PAI), and the results showed that synergistic mild-photothermal therapy/chemotherapy effectively alleviated tumor hypoxia. Finally, in vivo anti-tumor experiments have shown that synergistic therapy can effectively alleviate hypoxia and inhibit the growth of orthotopic gliomas.Conclusion: This work not only provides an effective means for real-time monitoring of the dynamic feedback between tumor hypoxia relief and therapeutic efficacy, but also offers a potential approach for the clinical treatment of gliomas.Keywords: gliomas, hypoxia relief, photothermal therapy, real-time monitoring, photoacoustic imaging
