Department of Pharmacy, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Mol Pharm. 2020 Sep 8;17(9):3151-3164. doi: 10.1021/acs.molpharmaceut.0c00077. Epub 2020 Aug 24.
Due to the abnormal tumor vasculature and dense stroma, there is limited tumor perfusion in the immunosuppressive tumor microenvironment (TME). In order to reshape tumor blood vessels and enhance the penetration of anticancer drugs into the tumor tissue, an anionic liposome nanosystem with a "sandwich" structure was prepared. The chemotherapeutic agent topotecan (TPT) was encapsulated in the lipid hydrophilic layer, and the sensitizer indocyanine green (ICG) was loaded into the hydrophobic layer. In addition, the positively charged vascular normalization drug erlotinib (ERL) was adsorbed to the outermost layer of the microenvironment. The nanosystem showed superior tumor permeability / experiments compared with the ERL-treated group. The nanosystem entered the tumor through normalization of blood vessels after the action of ERL. Ultrasound treatment improves the vascular permeability, allowing the nanoparticles to penetrate blood vessels and reach tumor cells. Finally, in addition to cytotoxic effects, TPT can also down-regulate the expression of HIF-1α and so prolong the vascular normalization time. These experimental results showed that the nanosystem effectively improves the tumor microenvironment. This work indicates the great potential of vascular normalization combined with sonodynamic therapy and chemotherapy to enhance efficiency.
由于肿瘤血管异常和基质致密，肿瘤在免疫抑制的肿瘤微环境（TME）中的灌注有限。为了重塑肿瘤血管并增强抗癌药物渗透到肿瘤组织中，制备了一种具有“三明治”结构的阴离子脂质体纳米系统。化疗药物拓扑替康（TPT）被包裹在脂质亲水层中，敏化剂吲哚菁绿（ICG）被装载在疏水性层中。此外，带正电荷的血管正常化药物厄洛替尼（ERL）被吸附到微环境的最外层。与 ERL 处理组相比，纳米系统显示出优异的肿瘤通透性/实验。纳米系统在 ERL 的作用下通过血管正常化进入肿瘤。超声处理可提高血管通透性，使纳米颗粒穿透血管并到达肿瘤细胞。最后，除了细胞毒性作用外，TPT 还可以下调 HIF-1α 的表达，从而延长血管正常化时间。这些实验结果表明，纳米系统有效地改善了肿瘤微环境。这项工作表明，血管正常化联合声动力学疗法和化疗具有提高效率的巨大潜力。
