Abstract：
Liposome formulations of the cancer drug doxorubicin have been developed to address the severe side effects that result from administration of this drug in a conventional formulation. Among them, thermosensitive liposomal doxorubicin presents enhanced tumor targeting and efficient drug release when combined with mild hyperthermia localized to the tumor site. Exploiting the radiosensitizing benefits of localized thermal therapy, the integration of radiation therapy with the thermally activated liposomal system is posited to amplify the anti-tumor efficacy. This study explored a synergistic therapeutic strategy that combines thermosensitive liposomal doxorubicin, mild hyperthermia, and radiotherapy, using an orthotopic murine model of breast cancer. The protocol of sequential multi-modal treatment, incorporating low-dose chemotherapy and radiotherapy, substantially postponed the progression of primary tumor growth in comparison to the application of monotherapy at elevated dosages. Improvements in unheated distant lesions were also observed. Furthermore, the toxicity associated with the combination treatment was comparable to that of either thermosensitive liposome treatment or radiation alone at low doses. These outcomes underscore the potential of multi-modal therapeutic strategies to refine treatment efficacy while concurrently diminishing adverse effects in the management of breast cancer, providing valuable insight for the future refinement of thermosensitive liposomal doxorubicin applications.
摘要：
已经开发了癌症药物多柔比星的脂质体制剂以解决在常规制剂中施用该药物导致的严重副作用。其中,热敏脂质体多柔比星与局部肿瘤部位的轻度热疗结合时，可增强肿瘤靶向性和有效的药物释放。利用局部热疗的放射增敏益处，放射治疗与热激活脂质体系统的整合被认为可以增强抗肿瘤功效。本研究探索了一种联合热敏脂质体阿霉素的协同治疗策略，轻度高热,和放射治疗，使用原位小鼠乳腺癌模型。序贯多模式治疗方案，结合低剂量化疗和放疗，与以升高的剂量应用单药治疗相比，实质上推迟了原发性肿瘤生长的进展。还观察到未加热的远处病变的改善。此外，联合治疗的毒性与热敏脂质体治疗或低剂量单独放疗的毒性相当.这些结果强调了多模式治疗策略在改善治疗效果同时减少乳腺癌治疗中的不良反应的潜力。为热敏脂质体阿霉素应用的未来改进提供有价值的见解。
