Sun Yifu, Li Ke, Li Chen, Zhang Ying, Zhao Duoyi
Department of Orthopedics, The Second Hospital of Jilin University, Changchun, China.
Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
Front Bioeng Biotechnol. 2020 Sep 15;8:573962. doi: 10.3389/fbioe.2020.573962. eCollection 2020.
The therapeutic effect of osteosarcoma (OS) has not made extraordinary progress in the past few decades. Oxaliplatin (OXA) is a widely used clinical anti-tumor drug. Recent studies have shown that OXA can trigger anti-tumor immunity by inducing immunogenic death (ICD). Alendronate (ALN) has been used to threaten the skeletal system tumors because of the unique bone affinity and the ability to inhibit bone destruction. In this study, we co-loaded OXA and ALN on mPEG45-PLV19 thermo-sensitive hydrogel to perform treatment on the mouse OS model. Slowly released OXA can induce immunogenic death of tumor cells. At the same time, thermo-sensitive hydrogels can induce the accumulation of cytotoxic T lymphocytes. Besides, ALN could synergistically diminish tumors and prevent bone destruction. This system could synergistically inhibit the progression of OS and lung metastasis and has no toxicity to various organs throughout the body.
在过去几十年中,骨肉瘤(OS)的治疗效果并未取得显著进展。奥沙利铂(OXA)是一种广泛应用于临床的抗肿瘤药物。最近的研究表明,OXA可通过诱导免疫原性细胞死亡(ICD)引发抗肿瘤免疫。阿仑膦酸盐(ALN)因其独特的骨亲和力和抑制骨破坏的能力,已被用于治疗骨骼系统肿瘤。在本研究中,我们将OXA和ALN共同负载于mPEG45 - PLV19热敏水凝胶上,对小鼠OS模型进行治疗。缓慢释放的OXA可诱导肿瘤细胞发生免疫原性死亡。同时,热敏水凝胶可诱导细胞毒性T淋巴细胞的聚集。此外,ALN可协同缩小肿瘤并防止骨破坏。该系统可协同抑制OS的进展和肺转移,且对全身各器官均无毒性。