College of Materials Science and Opto-Electronic Technology, University of Chinese Academy of Sciences, Beijing 100049, China.
Department of Nanomedicine, Houston Methodist Hospital Research Institute, Houston, TX 77030, USA.
Theranostics. 2018 Jan 1;8(1):31-44. doi: 10.7150/thno.21342. eCollection 2018.
Aptamers have the potential to be used as targeting ligands for cancer treatment as they form unique spatial structures. In this study, a DNA aptamer (T1) that accumulates in the tumor microenvironment was identified through selection and validation in breast cancer models. The use of T1 as a targeting ligand was evaluated by conjugating the aptamer to liposomal doxorubicin. T1 exhibited a high affinity for both tumor cells and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Treatment with T1 targeted doxorubicin liposomes triggered apoptosis of breast cancer cells and PMN-MDSCs. Suppression of PMN-MDSCs, which serve an immunosuppressive function, leads to increased intratumoral infiltration of cytotoxic T cells. The cytotoxic and immunomodulatory effects of T1-liposomes resulted in superior therapeutic efficacy compared to treatment with untargeted liposomes, highlighting the promise of T1 as a targeting ligand in cancer therapy.
适体具有作为癌症治疗的靶向配体的潜力，因为它们形成独特的空间结构。在这项研究中，通过在乳腺癌模型中的选择和验证，鉴定了一种在肿瘤微环境中积累的 DNA 适体（T1）。通过将适体与脂质体阿霉素缀合来评估 T1 作为靶向配体的用途。T1 表现出对肿瘤细胞和多形核髓系来源的抑制性细胞（PMN-MDSCs）的高亲和力。用 T1 靶向的阿霉素脂质体处理触发乳腺癌细胞和 PMN-MDSC 的细胞凋亡。PMN-MDSC 的抑制作用，其具有免疫抑制功能，导致细胞毒性 T 细胞在肿瘤内的浸润增加。T1-脂质体的细胞毒性和免疫调节作用导致比用非靶向脂质体治疗具有更好的治疗效果，突出了 T1 作为癌症治疗的靶向配体的潜力。
