Longjiang Zhou,Haitao Xiang,Susu Liu,Honglin Chen,Yuanwei Yang,Jianyong Zhang,Wei Cai
Purpose 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.
Immunotherapy holds significant promise to completely eliminate tumor, yet lack of timely evaluation of immune responses, which challenged by inherent lagging and pseudoprogression during immunotherapy. Immune-vascular crosstalk (IVC), an enhancement ring for the mutual regulation linking tumor vascular normalization with immune remodeling forms, emerging as a systematic indicator for immunotherapy outcomes, necessitates timely, non-invasive, and early detection of its status to enhance clinical benefits. Herein, positive and negative loop models of tumor IVC were established using different degree of photothermal therapy (PTT) based on NaBiF 4 :Gd@PDA@PEG nanoprobes. Multi-functional magnetic resonance imaging, including fast spoiled gradient-recalled (FSPGR), time-resolved imaging of contrast kinetics (TRICKs) and dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI), was applied to dynamically reflect normalized/ablated tumor vasculature, well-matched increased/decreased immune response corresponding to different status of IVC, confirmed by pathology results. This study proposes a novel biological method to noninvasively detect the positive/negative IVC loop, paving the visualized way for immunotherapy assessed benefits, which is expected to be extended to clinical translation.
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