Research Institute, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi-Do 10408, Republic of Korea.
Research Institute, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi-Do 10408, Republic of Korea.
J Control Release. 2024 Dec;376:108-122. doi: 10.1016/j.jconrel.2024.10.008. Epub 2024 Oct 10.
Immune checkpoint inhibitors (ICIs) are innovative immunotherapeutic agents for cancer. However, their low therapeutic efficacy in patients with large or rapidly growing tumors, along with their high cost, represents a notable limitation in their clinical applications. Therefore, new and safe strategies must be developed to enhance the therapeutic efficacy of ICIs in clinical settings. In this study, we developed a near-infrared (NIR) fluorescent dye-loaded activatable theranostic nanogel (NATNgel) for precision imaging-guided photodynamic therapy (PDT) and combined immunotherapy for rapidly growing tumors. Although NIR fluorescence and phototoxicity of NATNgel are strongly quenched, these can be selectively activated inside target tumor cells. A high tumor-to-background ratio (7.31 ± 1.40) in NIR fluorescence imaging could be achieved in NATNgel-treated mice, enabling real-time image-guided PDT. The combination of PDT and anti-PD-1 antibody therapy resulted in complete tumor regression. Histopathological evaluation of major organs and blood chemistry analysis revealed no side effects of the combined treatment regimen. In addition, the combination treatment completely suppressed the growth of rechallenged tumors. Overall, NATNgel is a safe and promising theranostic material for precision imaging-guided PDT and enhanced immunotherapy.
免疫检查点抑制剂（ICIs）是癌症的创新性免疫治疗药物。然而，它们在大肿瘤或快速生长的肿瘤患者中的治疗效果较低，加上其高昂的成本，这是它们在临床应用中的一个显著限制。因此，必须开发新的、安全的策略，以提高 ICI 在临床环境中的治疗效果。在本研究中，我们开发了一种近红外（NIR）荧光染料负载的可激活治疗性纳米凝胶（NATNgel），用于精确成像引导的光动力疗法（PDT）和联合免疫治疗快速生长的肿瘤。尽管 NATNgel 的近红外荧光和光毒性被强烈猝灭，但这些可以在靶肿瘤细胞内被选择性激活。在接受 NATNgel 治疗的小鼠中，NIR 荧光成像可实现高肿瘤与背景比（7.31±1.40），从而实现实时图像引导的 PDT。PDT 联合抗 PD-1 抗体治疗导致肿瘤完全消退。对主要器官的组织病理学评估和血液化学分析显示联合治疗方案无副作用。此外，联合治疗完全抑制了复发性肿瘤的生长。总的来说，NATNgel 是一种安全且有前途的用于精确成像引导 PDT 和增强免疫治疗的治疗诊断材料。
