Abstract：
The aberrant tumor microenvironment (TME), especially immature and leaky vessels, prevents the penetration and accumulation of chemotherapeutics and results in the failure of chemotherapy to treat gynecologic cancer. Herein, dexamethasone (Dex), a glucocorticoid steroid used to moderate tumor extracellular matrix and normalize vessels, was enclosed within a biocompatible material known as poly(lactic-co-glycolic acid) (PLGA), and the obtained Dex@PLGA was further coated with a mouse cervical cancer cell membrane (CM). The formulated Dex@PLGA-CM nanoparticles showed efficient extravascular diffusion within the tumor owing to the homologous targeting abilities inherited from the source cancer cells. The Dex@PLGA-CM nanoparticles greatly reshaped the TME, enhancing the penetration of Doxil and thus markedly improving the therapeutic effect of this drug against cervical cancers. Excitingly, the Dex@PLGA-CM nanoparticles coated with mouse ovarian cancer cell membranes also promoted Doxil-mediated chemotherapy effects in metastatic ovarian cancer when administered intraperitoneally. This work presents an effective nanomedicine for the efficient modification of the TME to enhance the effects of gynecologic cancer chemotherapy.
摘要：
异常肿瘤微环境（TME），尤其是不成熟和漏水的血管，防止化疗药物的渗透和积累，并导致化疗治疗妇科癌症的失败。在这里，地塞米松（Dex），一种用于缓解肿瘤细胞外基质和使血管正常化的糖皮质激素类固醇，被封闭在生物相容性材料中，称为聚（乳酸-共-乙醇酸）（PLGA），并将获得的Dex@PLGA进一步用小鼠宫颈癌细胞膜(CM)包被。由于从源癌细胞遗传的同源靶向能力，配制的Dex@PLGA-CM纳米颗粒在肿瘤内显示出有效的血管外扩散。Dex@PLGA-CM纳米粒子极大地重塑了TME，增强Doxil的渗透，从而显着提高该药物对宫颈癌的治疗效果。令人兴奋的是,当腹膜内给药时,涂有小鼠卵巢癌细胞膜的Dex@PLGA-CM纳米颗粒也促进了Doxil介导的转移性卵巢癌化疗效果.这项工作提出了一种有效的纳米药物，用于有效修饰TME以增强妇科癌症化疗的效果。
