Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province 110042, China.
The Graduate School, Dalian Medical University, Dalian, Liaoning Province 116044, China.
Biomed Pharmacother. 2017 Jun;90:872-879. doi: 10.1016/j.biopha.2017.04.004. Epub 2017 Apr 23.
The present work is an effort to explore the poloxamer-modified trimethyl chitosan (TMC) encapsulated MTX for osteosarcoma treatment in order to improve the therapeutic efficacy and minimize severe toxicity associated with the clinical usage of MTX. The methotrexate-loaded pluronic-chitosan nanoparticles (MTCN) was nanosized and exhibited a controlled release of drug from the carrier system. The MTCN showed higher accumulation in cell cytoplasm region evident by the high red fluorescence indicating its uptake through energy-dependent endocytosis process. MTCN exhibited the increased cytotoxicity in MG63 cells compared free MTX due to its enhanced cellular uptake. Especially, MTCN exhibited a superior apoptosis effect with bright chromatin condensation and nuclear fragmentation was observed and showed remarkably higher apoptosis (∼48%) compared to that of free drug. The results of this investigation clearly demonstrate that the poloxamer-modified trimethyl chitosan (TMC) seems to have a great potential as a drug carrier in cancer chemotherapy. The present research work offers immense scope for further exploitation of poloxamer-modified trimethyl chitosan (TMC) in future for the development of nanoparticulate drug delivery system for cancer chemotherapy.
本研究旨在探索泊洛沙姆修饰的三甲基壳聚糖（TMC）包载 MTX 用于骨肉瘤治疗，以提高治疗效果并降低 MTX 临床应用相关的严重毒性。载 MTX 的泊洛沙姆-壳聚糖纳米粒（MTCN）呈纳米级并表现出药物从载体系统的控制释放。MTCN 显示出更高的细胞内积聚，这可以通过高红色荧光来证明，表明其通过能量依赖的内吞作用过程被摄取。与游离 MTX 相比，MTCN 在 MG63 细胞中表现出更高的细胞毒性，这是由于其增强的细胞摄取。特别是，MTCN 表现出优越的凋亡作用，观察到明显的染色质浓缩和核片段化，与游离药物相比，凋亡率显著提高（约 48%）。本研究结果清楚地表明，泊洛沙姆修饰的三甲基壳聚糖（TMC）作为癌症化疗的药物载体具有很大的潜力。本研究工作为进一步开发泊洛沙姆修饰的三甲基壳聚糖（TMC）在未来癌症化疗的纳米药物递送系统中的应用提供了广阔的前景。
