Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Institute of Pharmacy, Pharmaceutical College of Henan University, Kaifeng 475004, China.
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Department of Chemical Defense, Institute of NBC Defense, Beijing 102205, China.
Int J Pharm. 2021 May 15;601:120572. doi: 10.1016/j.ijpharm.2021.120572. Epub 2021 Apr 5.
Sonodynamic therapy (SDT) has been tried for cancer treatment; however, sonosensitizers are usually administered by injection, leading to low distribution in the tumor tissue and compromised therapeutic effect, even serious side effect. Here, we combined cationic liposomal hydroxycamptothecin (CLH) and 5-aminolevulinic acid (5-ALA) via intratracheal (i.t.) administration for the chemo-sonodynamic (Chemo-SDT) therapy of metastatic lung cancer. CLH was prepared from HCPT and the lipid mixture of soybean lecithin/cholesterol/octadecylamine with a film method. The optimal pre-incubation time of 5-ALA with tumor cells before ultrasound exposure was 4 h, for sake of sonosensitizer accumulation, i.e., protoporphyrin IX, the metabolite of 5-ALA. In vitro studies showed the higher cytotoxicity of Chemo-SDT compared to the other treatments, including i.t. CLH, intravenous (i.v.) CLH, and SDT alone. The combination of pulmonary delivery and Chemo-SDT showed the highest anticancer effect among the treatments on the metastatic lung tumor-bearing mice, which was judged according to the tumor appearance and pathological sections. The major anticancer mechanism of Chemo-SDT included the improved apoptosis of cancer cells and the enhanced production of reactive oxygen species, and more importantly, the synergy of chemotherapy and SDT. Pulmonary delivery of chemotherapeutics and sonosensitizers is a promising strategy for the treatment of lung cancer.
声动力学疗法 (SDT) 已被尝试用于癌症治疗；然而，声敏剂通常通过注射给药，导致在肿瘤组织中的分布较低，并降低治疗效果，甚至导致严重的副作用。在这里，我们通过气管内 (i.t.) 给药将阳离子脂质体羟基喜树碱 (CLH) 和 5-氨基酮戊酸 (5-ALA) 联合用于转移性肺癌的化疗-声动力学 (Chemo-SDT) 治疗。CLH 是通过薄膜法由 HCPT 和大豆卵磷脂/胆固醇/十八胺的脂质混合物制备的。为了声敏剂积聚，即 5-ALA 的代谢物原卟啉 IX，在超声暴露前，肿瘤细胞与 5-ALA 的最佳预孵育时间为 4 小时。体外研究表明，与其他治疗方法（包括气管内 CLH、静脉内 (i.v.) CLH 和单独 SDT）相比，Chemo-SDT 的细胞毒性更高。与其他治疗方法相比，肺部给药与 Chemo-SDT 的联合治疗在转移性肺肿瘤荷瘤小鼠中表现出最高的抗癌效果，这是根据肿瘤外观和病理切片判断的。Chemo-SDT 的主要抗癌机制包括增强癌细胞的凋亡和增加活性氧的产生，更重要的是，化疗和 SDT 的协同作用。化疗药物和声敏剂的肺部给药是治疗肺癌的一种有前途的策略。
