Jia Siyu, Chen Yaohui, Zhuo Can, Hu Ming, Zhang Chengwei, Cai Huili, Li Xinzhi, Chen Haidan, Yu Xiang
The First College of Clinical Medical Science, China Three Gorges University, Yichang, China; Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China; Department of Spinal Surgery, Yichang Central People's Hospital, Yichang, China.
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China.
Colloids Surf B Biointerfaces. 2025 May;249:114512. doi: 10.1016/j.colsurfb.2025.114512. Epub 2025 Jan 13.
Osteosarcoma (OS) is the most common primary bone malignancy characterized by deposition of an immature osteoid matrix. OS treatment has proven challenging because of the high risk of metastatic progression and recurrence after chemotherapy. Melittin (MLT) is recognized as a potential antitumor candidate to overcome chemotherapy resistance and provoke superior immunostimulatory effects. However, the application of MLT to OS is hampered by severe toxic side effects and a lack of tumor-targeting ability. Herein, a self-assembled nanopolymer named LC09-MLT@F127 was developed by binding MLT with F127 micelles and then modifying an aptamer (LC09) for targeted drug delivery during OS treatment. LC09-MLT@F127 exhibited significant OS-targeting ability in vitro and in vivo owing to the aptamer LC09 decoration. Moreover, LC09-MLT@F127 significantly reduced the hemolytic toxicity of MLT while maintaining its tumor-killing ability. In an orthotopic transplantation model of OS, LC09-MLT@F127 induced immunogenic cell death and facilitated the maturation of dendritic cells (DCs), thereby resulting in the activation of tumor-specific immune responses and the inhibition of OS deterioration. Taken together, these finding suggest that LC09-MLT@F127 may be an encouraging MLT-based immunotherapy option for OS.
骨肉瘤（OS）是最常见的原发性骨恶性肿瘤，其特征是不成熟类骨质基质的沉积。由于化疗后转移进展和复发的高风险，OS治疗已被证明具有挑战性。蜂毒肽（MLT）被认为是一种潜在的抗肿瘤候选物，可克服化疗耐药性并引发卓越的免疫刺激作用。然而，MLT在OS中的应用受到严重毒副作用和缺乏肿瘤靶向能力的阻碍。在此，通过将MLT与F127胶束结合，然后修饰一种适配体（LC09）以在OS治疗期间进行靶向药物递送，开发了一种名为LC09-MLT@F127的自组装纳米聚合物。由于适配体LC09的修饰，LC09-MLT@F127在体外和体内均表现出显著的OS靶向能力。此外，LC09-MLT@F127在保持其肿瘤杀伤能力的同时，显著降低了MLT的溶血毒性。在OS的原位移植模型中，LC09-MLT@F127诱导免疫原性细胞死亡并促进树突状细胞（DC）的成熟，从而导致肿瘤特异性免疫反应的激活和OS恶化的抑制。综上所述，这些发现表明LC09-MLT@F127可能是一种令人鼓舞的基于MLT的OS免疫治疗选择。
