Zhou Lanzhu, Wu Jun, Sun Zhe, Wang Wenzhong
Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
Front Pharmacol. 2022 Jul 22;13:934632. doi: 10.3389/fphar.2022.934632. eCollection 2022.
Laryngeal carcinoma is the most common head and neck malignancy globally, and chemotherapy is still the most common treatment for this type of carcinoma. Monotherapy has become powerless because of the lack of drugs in the anticancer agent library, the difficult process of new drug discovery, and the widespread drug resistance. Combination therapy with two agents, in particular Chinese herbal medicines with chemotherapy drugs, is a potential alternative to chemotherapy alone. However, combination therapy faces difficulties in delivering multiple drugs to tumor tissue in a precise ratio. Here, a cocktail polymeric prodrug micelle (PHPPM) was developed using an oxidation and reduction dual-responsive polymeric paclitaxel (PTX) and polymeric honokiol (HK) prodrugs. Both of them were obtained by covalently conjugating the drug to dextran diselenium bonds. Following optimization and characterization, the PHPPM with the precise mass ratio of PTX and HK was obtained, enabling ratiometric drug loading, synchronized drug release in response to tumor high-level reactive oxygen species and glutathione environment, long blood circulation, and high tumor accumulation. This co-delivery system can effectively inhibit laryngeal carcinoma growth and . Codelivery of chemotherapy agents and Chinese herbal medicine with a precise ratio and controlled release of the two drugs at the tumor site provides an effective approach to clinical therapy for other laryngeal carcinomas.
喉癌是全球最常见的头颈部恶性肿瘤，化疗仍是这类癌症最常用的治疗方法。由于抗癌药物库中缺乏药物、新药研发过程困难以及广泛存在的耐药性，单一疗法已无能为力。两种药物的联合治疗，特别是中药与化疗药物的联合治疗，是单独化疗的一种潜在替代方案。然而，联合治疗在以精确比例将多种药物递送至肿瘤组织方面面临困难。在此，利用氧化还原双响应性聚合物紫杉醇（PTX）和厚朴酚（HK）前药开发了一种鸡尾酒式聚合物前药胶束（PHPPM）。它们均通过将药物共价连接到葡聚糖二硒键上获得。经过优化和表征，得到了PTX和HK质量比精确的PHPPM，实现了比例式载药、响应肿瘤高水平活性氧和谷胱甘肽环境的同步药物释放、长循环以及高肿瘤蓄积。这种共递送系统能有效抑制喉癌生长。以精确比例共同递送化疗药物和中药，并在肿瘤部位实现两种药物的控释，为其他喉癌的临床治疗提供了一种有效方法。
