Department of Surgery, Stanford University, 453 Quarry Road, Palo Alto, CA, 94304, USA.
Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA, 02155, USA.
Pediatr Surg Int. 2023 Jul 27;39(1):241. doi: 10.1007/s00383-023-05523-w.
Tumor-associated macrophages are present within neuroblastoma, and interferon-gamma (IFN-γ) can polarize macrophages into cancer-inhibiting M1 type. We hypothesize that treating neuroblastoma with interferon-gamma (IFN-γ) can suppress tumor growth, and the concurrent treatment with IFN-γ and vincristine can lead to enhanced tumor killing as compared to vincristine alone.
We loaded IFN-γ or vincristine into silk biomaterials and recorded the amount released over time. Orthotopic, syngeneic neuroblastoma xenografts were generated by injecting 9464D cells into adrenal gland of C57BL/6 mice, and IFN-γ-loaded and/or vincristine-loaded silk biomaterials were implanted into the tumor once the tumors reached 100 mm. Drug release at different timepoints was measured and tumor growth after different treatments were compared.
1-2% of IFN-γ and 70% of vincristine were released from the biomaterials by the fifth day. Combining IFN-γ and vincristine significantly slowed tumor growth as compared to the controls (12.2 ± 2.7 days to reach 800 mm versus 5.7 ± 1.2 days, p = 0.01), and IFN-γ alone also delayed tumor growth as compared to the controls (10.9 ± 1.5 days versus 5.7 ± 1.2 days, p = 0.001). Hematoxylin and eosin staining demonstrated tumor necrosis adjacent to the drug-loaded silk biomaterials.
Local delivery of sustained release IFN-γ can inhibit neuroblastoma tumor growth by itself and in combination with vincristine.
神经母细胞瘤中存在肿瘤相关巨噬细胞，干扰素-γ（IFN-γ）可以将巨噬细胞极化为抑制癌症的 M1 型。我们假设用干扰素-γ（IFN-γ）治疗神经母细胞瘤可以抑制肿瘤生长，并且与单独使用长春新碱相比，IFN-γ 与长春新碱同时治疗可以导致更强的肿瘤杀伤作用。
我们将 IFN-γ 或长春新碱载入丝素生物材料中，并记录随时间的释放量。通过将 9464D 细胞注射到 C57BL/6 小鼠的肾上腺中来生成原位、同基因神经母细胞瘤异种移植物，并且一旦肿瘤达到 100mm 就将 IFN-γ 负载和/或长春新碱负载的丝素生物材料植入肿瘤中。测量不同时间点的药物释放情况，并比较不同治疗后的肿瘤生长情况。
第 5 天，生物材料中释放了 1-2%的 IFN-γ 和 70%的长春新碱。与对照组相比，联合使用 IFN-γ 和长春新碱显著减缓了肿瘤生长（达到 800mm 的时间为 12.2±2.7 天，而对照组为 5.7±1.2 天，p=0.01），并且与对照组相比，IFN-γ 单独使用也延迟了肿瘤生长（达到 800mm 的时间为 10.9±1.5 天，而对照组为 5.7±1.2 天，p=0.001）。苏木精和伊红染色显示药物负载丝素生物材料附近的肿瘤坏死。
局部持续释放 IFN-γ 可以单独或与长春新碱联合抑制神经母细胞瘤肿瘤生长。
