CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
Int J Pharm. 2021 Feb 1;594:120183. doi: 10.1016/j.ijpharm.2020.120183. Epub 2020 Dec 18.
Lymph node metastases in cancer patients are associated with high aggressiveness, poor prognosis, and short survival time. The chemokine receptor 4 (CXCR4)/stroma derived factor 1α (CXCL12) biological axis plays a critical role in the spread of cancer cells. Designing effective delivery systems that can successfully deliver CXCR4 antagonists to lymph nodes, which are rich in CXCR4-overexpressing cancer cells, for controlling cancer metastasis remain challenging. In this study, we demonstrated that such a challenge may be alleviated by developing nanometer-sized polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles for the co-delivery of the CXCR4 antagonistic peptide E5 and doxorubicin (M-E5-Dox). This nanomicelle platform enables the preferential accumulation of cargos into lymph nodes and thus can better inhibit cancer metastasis and enhance antitumor efficacy than either free drugs or single drug-loaded micelles in breast cancer-bearing mouse models. Hence, M-E5-Dox is expected to be a potential therapeutic agent that would improve the clinical benefits of breast cancer therapy and treatment of various CXCR4-overexpressing malignancies.
癌症患者的淋巴结转移与侵袭性高、预后差和生存时间短有关。趋化因子受体 4（CXCR4）/基质衍生因子 1α（CXCL12）生物轴在癌细胞的扩散中起着关键作用。设计有效的递药系统，成功地将 CXCR4 拮抗剂递送到富含过表达 CXCR4 的癌细胞的淋巴结中，以控制癌症转移仍然具有挑战性。在这项研究中，我们通过开发纳米级聚乙二醇-磷脂酰乙醇胺（PEG-PE）胶束来共递送 CXCR4 拮抗肽 E5 和阿霉素（M-E5-Dox），证明了这一挑战可能会得到缓解。这种纳米胶束平台使载药优先积累到淋巴结中，从而比游离药物或单载药胶束在乳腺癌荷瘤小鼠模型中更好地抑制癌症转移并增强抗肿瘤疗效。因此，M-E5-Dox 有望成为一种潜在的治疗剂，将提高乳腺癌治疗和治疗各种过表达 CXCR4 的恶性肿瘤的临床获益。
