Ifosfamide-loaded poly (lactic-co-glycolic acid) PLGA-dextran polymeric nanoparticles to improve the antitumor efficacy in Osteosarcoma.
Ifosfamide-loaded poly (lactic-co-glycolic acid) PLGA-dextran polymeric nanoparticles to improve the antitumor efficacy in Osteosarcoma.
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DOI：
10.1186/s12885-015-1735-6
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发表时间：
2015-10-21
期刊：
影响因子：
3.8
通讯作者：
Lin XJ
中科院分区：
文献类型：
--
作者：
Chen B;Yang JZ;Wang LF;Zhang YJ;Lin XJ
骨肉瘤是一种典型的骨癌，主要影响青少年。药物的治疗活性受到其严重的药物相关毒性的限制，因此，在肿瘤中毒性较小且高效的治疗方法是至关重要的。在这项研究中，异环磷酰胺负载聚（乳酸-羟基乙酸）（PLGA）-葡聚糖聚合物纳米粒（PD/IFS）的开发和研究其对多种骨肉瘤癌细胞的抗癌疗效。对载药纳米粒进行了物理和生物学表征。配制的PD/IFS显示出高的载药量，并显示出pH敏感的释放模式，具有IFS的持续释放曲线。PD/IFS纳米粒在MG 63和Saos-2癌细胞中以浓度依赖性方式显示出与游离IFS溶液相当的显著体外抗癌活性。PLGA-葡聚糖本身不影响癌细胞的细胞活力，表明其具有优异的生物相容性。该制剂在两种癌细胞中均表现出显著更高的PARP和半胱天冬酶-3/7表达。我们的研究成功地证明了抗肿瘤剂的纳米颗粒包封将增加治疗功效并表现出更大的凋亡和细胞死亡诱导。
Osteosarcoma is a typical bone cancer that primarily affects adolescents. The therapeutic activity of drugs is limited by their severe drug-related toxicities, therefore, a therapeutic approach which is less toxic and highly effective in tumor is of utmost importance. In this study, ifosfamide-loaded poly (lactic-co-glycolic acid) (PLGA)-dextran polymeric nanoparticles (PD/IFS) was developed and studied its anticancer efficacy against multiple osteosarcoma cancer cells. The drug-loaded nanoparticle was characterized for physical and biological characterizations. The formulated PD/IFS showed a high drug loading capacity and displayed a pH-sensitive release pattern, with a sustained release profile of the IFS. PD/IFS nanoparticles exhibited remarkable in vitro anticancer activity comparable to that of free IFS solution in a concentration dependent manner in MG63 and Saos-2 cancer cells. PLGA-dextran by itself did not affect cell viability of cancer cells indicating its excellent biocompatibility. The formulation exhibited significantly higher PARP and caspase-3/7 expression in both the cancer cells. Our study successfully demonstrated that nanoparticulate encapsulation of antitumor agent will increase the therapeutic efficacy and exhibit a greater induction of apoptosis and cell death.