Gogoi Manashjit, Jaiswal Manish K, Sarma Haladhar Dev, Bahadur Dhirendra, Banerjee Rinti
Nanomedicine Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai-400076, India.
Integr Biol (Camb). 2017 Jun 19;9(6):555-565. doi: 10.1039/c6ib00234j.
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 LaSrMnO (LSMO) and iron oxide (FeO) 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 mm) whereas the double dose treatment reduced the tumour growth by 3.6 fold (mean tumour volume 1045 ± 440 mm) compared to their corresponding control (mean tumour volume 3782 ± 515 mm). 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.
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式正变得越来越重要。然而，由于组织过热，在临床环境中控制和维持最佳热疗是主要挑战。为克服这一问题，我们开发了一种新型磁性脂质体制剂，共包封了葡聚糖包被的LaSrMnO（LSMO）和氧化铁（FeO）纳米颗粒的双相悬浮液，用于自我控制热疗和化疗。然而，需要解决对新开发制剂的生物相容性和安全性的普遍担忧。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及治疗评估研究。对磁性脂质体制剂进行生物相容性研究，以评估在瑞士小鼠静脉注射磁性脂质体后是否有初步全身毒性迹象。在携带纤维肉瘤肿瘤的小鼠模型中评估磁性脂质体制剂的治疗效果。携带纤维肉瘤肿瘤的小鼠在瘤内注射单剂量或双剂量的磁性脂质体（有或没有化疗药物紫杉醇）后接受热疗。单剂量给药后用载药磁性脂质体进行热疗（三次脉冲，每次间隔3天）使肿瘤生长减少了2.5倍（平均肿瘤体积2356±550立方毫米），而双剂量治疗使肿瘤生长减少了3.6倍（平均肿瘤体积1045±440立方毫米），相比相应对照组（平均肿瘤体积3782±515立方毫米）。在肿瘤疗效研究结束时，研究了小鼠残余肿瘤组织和重要器官中磁性纳米颗粒的存在情况。在研究期间未观察到磁性脂质体从肿瘤部位向身体其他重要器官有明显的浸出或排出，这再次表明新型磁性脂质体制剂有可能发展成为治疗耐药或生理脆弱癌症的有效方式。
