Dombroski Jenna A, Jyotsana Nidhi, Crews Davis W, Zhang Zhenjiang, King Michael R
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States.
Langmuir. 2020 Jun 16;36(23):6531-6539. doi: 10.1021/acs.langmuir.0c00947. Epub 2020 Jun 5.
Breast cancer is the most common cancer among women in the United States, with late stages associated with the lowest survival rates. The latest stage, defined as metastasis, accounts for 90% of all cancer-related deaths. There is a strong need to develop antimetastatic therapies. TRAIL, or TNF-related apoptosis inducing ligand, has been used as an antimetastatic therapy in the past, and conjugating TRAIL to nanoscale liposomes has been shown to enhance its targeting efficacy. When circulating tumor cells (CTCs) released during metastasis are exposed to TRAIL-conjugated liposomes and physiologically relevant fluid shear stress, this results in rapid cancer cell destruction into cell fragments. We sought to artificially recreate this phenomenon using probe sonication to mechanically disrupt cancer cells and characterized the resulting cell fragments, termed "tumor nano-lysate", with respect to size, charge, morphology, and composition. Furthermore, an in vivo pilot study was performed to investigate the efficacy of tumor nano-lysate as a preventative vaccine for breast cancer in an immunocompetent mouse model.
乳腺癌是美国女性中最常见的癌症，晚期乳腺癌的生存率最低。最新阶段定义为转移，占所有癌症相关死亡的90%。迫切需要开发抗转移疗法。TRAIL，即肿瘤坏死因子相关凋亡诱导配体，过去一直被用作抗转移疗法，并且已证明将TRAIL与纳米级脂质体结合可提高其靶向疗效。当转移过程中释放的循环肿瘤细胞（CTC）暴露于TRAIL偶联脂质体和生理相关的流体剪切应力时，这会导致癌细胞迅速破坏成细胞碎片。我们试图通过探针超声处理人工重现这一现象，以机械破坏癌细胞，并对产生的细胞碎片（称为“肿瘤纳米裂解物”）的大小、电荷、形态和组成进行表征。此外，还进行了一项体内初步研究，以调查肿瘤纳米裂解物作为免疫活性小鼠模型中乳腺癌预防性疫苗的疗效。
