Department of Central Laboratory, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, Huai'an 223300, China.
Department of Clinical Oncology, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, Huai'an 223300, China.
ACS Appl Mater Interfaces. 2020 Oct 21;12(42):47330-47341. doi: 10.1021/acsami.0c15419. Epub 2020 Sep 30.
Poor prognosis of esophageal cancer is associated with limited clinical treatment efficacy and lack of targeted therapies. With advances in nanomedicine, nanoparticle drug delivery systems play increasingly important roles in tumor treatment by enabling the simultaneous delivery of multiple therapeutic agents. We here propose a novel nanovector for targeted combination gene therapy and chemotherapy in esophageal cancer. A novel lipid nanovector (EYLN) was designed to carry the chemotherapy drug doxorubicin (Dox) and small interfering RNA against the lipid anabolic metabolism gene , which we previously showed to be significantly overexpressed in esophageal cancer tissues, and its interference inhibited the proliferation, invasion, and metastasis of esophageal cancer cells. This vector, EYLN-Dox/siLPCAT1, was further coated with leukocyte membranes to obtain mEYLNs-Dox/siLPCAT1. The particle size of the coated nanovector was approximately 136 nm, and the surface zeta potential was -21.18 mV. Compared with EYLNs-Dox/siLPCAT1, mEYLNs-Dox/siLPCAT1 were more easily internalized by esophageal cancer cells due to the LFA-1 highly expressed leukocyte membrane coating and showed significant inhibition of the proliferation, migration, and metastasis of esophageal cancer cells, along with their LPCAT1 expression, through more effective delivery of the drugs. Moreover, the nanovectors showed improved blood circulation time, tissue distribution, tumor targeting, and tumor suppression in a mouse model. Thus, combining chemo and gene therapy with this new nanodelivery system achieved greater therapeutic efficacy, providing a new strategy for the treatment of esophageal cancer.
食管癌预后不良与临床疗效有限和缺乏靶向治疗有关。随着纳米医学的进步，纳米颗粒药物递送系统通过同时递送多种治疗剂，在肿瘤治疗中发挥着越来越重要的作用。我们在此提出了一种用于食管癌靶向联合基因治疗和化疗的新型纳米载体。设计了一种新型脂质纳米载体（EYLN），用于携带化疗药物阿霉素（Dox）和针对脂质合成代谢基因的小干扰 RNA，我们之前的研究表明该基因在食管癌组织中显著过表达，其干扰抑制了食管癌细胞的增殖、侵袭和转移。该载体 EYLN-Dox/siLPCAT1 进一步用白细胞膜包被以获得 mEYLNs-Dox/siLPCAT1。包被纳米载体的粒径约为 136nm，表面 zeta 电位为-21.18mV。与 EYLN-Dox/siLPCAT1 相比，由于高表达的 LFA-1 白细胞膜包被，mEYLNs-Dox/siLPCAT1 更容易被食管癌细胞内化，并通过更有效地递送药物，显著抑制食管癌细胞的增殖、迁移和转移及其 LPCAT1 表达。此外，该纳米载体在小鼠模型中表现出改善的血液循环时间、组织分布、肿瘤靶向性和肿瘤抑制作用。因此，通过这种新的纳米递药系统将化疗和基因治疗相结合，取得了更大的治疗效果，为食管癌的治疗提供了一种新策略。
