Magnetic liposome-mediated combined chemotherapy and hyperthermia is gaining importance as an effective therapeutic modality for cancer. However, control and maintenance of optimum hyperthermia are major challenges in clinical settings due to the overheating of tissues. To overcome this problem, we developed a novel magnetic liposomes formulation co-entrapping a dextran coated biphasic suspension of La0.75Sr0.25MnO3 (LSMO) and iron oxide (Fe3O4) nanoparticles for self-controlled hyperthermia and chemotherapy. However, the general apprehension about biocompatibility and safety of the newly developed formulation needs to be addressed. In this work, in vitro and in vivo biocompatibility and therapeutic evaluation studies of the novel magnetic liposomes are reported. Biocompatibility study of the magnetic liposomes formulation was carried out to evaluate the signs of preliminary systemic toxicity, if any, following intravenous administration of the magnetic liposomes in Swiss mice. Therapeutic efficacy of the magnetic liposomes formulation was evaluated in the fibrosarcoma tumour bearing mouse model. Fibrosarcoma tumour-bearing mice were subjected to hyperthermia following intratumoral injection of single or double doses of the magnetic liposomes with or without chemotherapeutic drug paclitaxel. Hyperthermia (three spurts, each at 3 days interval) with drug loaded magnetic liposomes following single dose administration reduced the growth of tumours by 2.5 fold (mean tumour volume 2356 ± 550 mm3) whereas the double dose treatment reduced the tumour growth by 3.6 fold (mean tumour volume 1045 ± 440 mm3) compared to their corresponding control (mean tumour volume 3782 ± 515 mm3). At the end of the tumour efficacy studies, the presence of MNPs was studied in the remnant tumour tissues and vital organs of the mice. No significant leaching or drainage of the magnetic liposomes during the study was observed from the tumour site to the other vital organs of the body, suggesting again the potential of the novel magnetic liposomes formulation for possibility of developing as an effective modality for treatment of drug resistant or physiologically vulnerable cancer.

中文翻译：

---

磁性脂质体的生物相容性和治疗性评估设计用于自我控制的癌症热疗和化疗。

磁性脂质体介导的联合化疗和热疗作为一种有效的癌症治疗方法正变得越来越重要。然而，由于组织过热，控制和维持最佳热疗是临床环境中的主要挑战。为克服此问题，我们开发了一种新型磁性脂质体制剂，可共包埋葡聚糖包被的La0.75Sr0.25MnO3（LSMO）和氧化铁（Fe3O4）纳米颗粒的双相悬浮液，用于自控高温和化学疗法。然而，需要解决关于新开发制剂的生物相容性和安全性的普遍忧虑。在这项工作中，报道了新型磁性脂质体的体外和体内生物相容性和治疗评估研究。在瑞士小鼠中静脉内施用磁性脂质体后，进行了磁性脂质体制剂的生物相容性研究，以评估初步全身毒性（如果有）的迹象。在患有纤维肉瘤的小鼠模型中评估了磁性脂质体制剂的治疗功效。肿瘤内注射单剂量或双剂量的磁性脂质体（含或不含化疗药物紫杉醇）后，对纤维肉瘤肿瘤小鼠进行高温治疗。单次给药后用载有药物的磁性脂质体进行的高热治疗（每3天喷出3次），使肿瘤的生长减少了2.5倍（平均肿瘤体积2356±550 mm3），而双剂量治疗使肿瘤的生长减少了3倍。与相应的对照（平均肿瘤体积3782±515 mm3）相比，其抗癌能力提高了6倍（平均肿瘤体积1045±440 mm3）。在肿瘤功效研究结束时，研究了小鼠残余肿瘤组织和重要器官中MNP的存在。在研究过程中，没有观察到磁性脂质体从肿瘤部位到人体其他重要器官的明显浸出或引流，这再次表明了新型磁性脂质体制剂潜在的潜力，有望发展成为治疗耐药性的有效方法或生理上脆弱的癌症。