State Key Laboratory of Targeting Oncology, National Center for International Research of Bio-Targeting Theranostics, Guangxi Key Laboratory of Bio-Targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning 530021, China.
Int J Mol Sci. 2024 Feb 16;25(4):2353. doi: 10.3390/ijms25042353.
Oncolytic Newcastle disease virus is a new type of cancer immunotherapy drug. This paper proposes a scheme for delivering oncolytic viruses using hydrogel microneedles. Gelatin methacryloyl (GelMA) was synthesized by chemical grafting, and GelMA microneedles encapsulating oncolytic Newcastle disease virus (NDV) were prepared by micro-molding and photocrosslinking. The release and expression of NDV were tested by immunofluorescence and hemagglutination experiments. The experiments proved that GelMA was successfully synthesized and had hydrogel characteristics. NDV was evenly dispersed in the allantoic fluid without agglomeration, showing a characteristic virus morphology. NDV particle size was 257.4 ± 1.4 nm, zeta potential was -13.8 ± 0.5 mV, virus titer TCID50 was 10/mL, and PFU was 2 × 10/mL, which had a selective killing effect on human liver cancer cells in a dose and time-dependent manner. The NDV@GelMA microneedles were arranged in an orderly cone array, with uniform height and complete needle shape. The distribution of virus-like particles was observed on the surface. GelMA microneedles could successfully penetrate 5% agarose gel and nude mouse skin. Optimal preparation conditions were freeze-drying. We successfully prepared GelMA hydrogel microneedles containing NDV, which could effectively encapsulate NDV but did not detect the release of NDV.
溶瘤 Newcastle 疾病病毒是一种新型癌症免疫疗法药物。本文提出了一种使用水凝胶微针传递溶瘤病毒的方案。通过化学接枝合成明胶甲基丙烯酰(GelMA),通过微成型和光交联制备包封溶瘤 Newcastle 疾病病毒(NDV)的 GelMA 微针。通过免疫荧光和血凝实验测试 NDV 的释放和表达。实验证明成功合成了 GelMA 并具有水凝胶特性。NDV 在鸡胚尿囊液中均匀分散,没有聚集,呈现出特征性病毒形态。NDV 粒径为 257.4 ± 1.4nm,Zeta 电位为-13.8 ± 0.5mV,病毒滴度 TCID50 为 10/mL,PFU 为 2×10/mL,对人肝癌细胞具有剂量和时间依赖性的选择性杀伤作用。NDV@GelMA 微针呈有序的锥形阵列排列,高度均匀,针形完整。在表面观察到病毒样颗粒的分布。GelMA 微针能够成功穿透 5%琼脂糖凝胶和裸鼠皮肤。最佳制备条件为冷冻干燥。我们成功制备了含有 NDV 的 GelMA 水凝胶微针,能够有效包封 NDV,但未检测到 NDV 的释放。
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