Wang Xuehan, Allen Christine
Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada.
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada.
Drug Deliv Transl Res. 2025 Mar;15(3):1011-1022. doi: 10.1007/s13346-024-01654-2. Epub 2024 Jul 8.
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.
已经开发出癌症药物阿霉素的脂质体制剂，以解决使用传统制剂给药该药物时产生的严重副作用。其中，热敏脂质体阿霉素与局限于肿瘤部位的轻度热疗相结合时，具有增强的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，将放射治疗与热激活脂质体系统相结合被认为可以增强抗肿瘤疗效。本研究使用原位乳腺癌小鼠模型，探索了一种将热敏脂质体阿霉素、轻度热疗和放射治疗相结合的协同治疗策略。与高剂量单一疗法相比，纳入低剂量化疗和放射治疗的序贯多模式治疗方案显著延缓了原发性肿瘤生长的进展。在未加热的远处病灶中也观察到了改善。此外，联合治疗的毒性与低剂量热敏脂质体治疗或单独放疗的毒性相当。这些结果强调了多模式治疗策略在提高乳腺癌治疗效果同时减少不良反应方面的潜力，为未来改进热敏脂质体阿霉素的应用提供了有价值的见解。
