Doxorubicin loaded Polymeric Nanoparticulate Delivery System to overcome drug resistance in osteosarcoma.
Doxorubicin loaded Polymeric Nanoparticulate Delivery System to overcome drug resistance in osteosarcoma.
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DOI：
10.1186/1471-2407-9-399
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发表时间：
2009-11-16
期刊：
影响因子：
3.8
通讯作者：
Duan Z
中科院分区：
文献类型：
--
作者：
Susa M;Iyer AK;Ryu K;Hornicek FJ;Mankin H;Amiji MM;Duan Z
耐药性是骨肉瘤化疗有效性的主要障碍。尽管在20世纪80年代早期引入新辅助治疗后，化疗显著改善了骨肉瘤患者的预后，但其结果已经达到约70%的5年生存率。其余30%的患者最终对多种类型的化疗产生耐药性。为了克服传统化疗药物的剂量限制性副作用和多药耐药（MDR）肿瘤细胞引起的治疗失败，我们探索了将阿霉素负载到生物相容性，脂质修饰的葡聚糖基聚合物纳米颗粒上的可能性，并评估了疗效。将多柔比星装载到基于脂质改性葡聚糖的聚合物纳米系统上。分析了各种浓度的单独的阿霉素或纳米颗粒负载的阿霉素对KHOS、KH 0 SR 2、U-2 OS和U-20 SR 2细胞的作用。还分析了对药物保留、免疫荧光、Pgp表达和诱导细胞凋亡的影响。载阿霉素的葡聚糖纳米粒通过Pgp非依赖性途径增加多药耐药骨肉瘤细胞核内药物蓄积量，对骨肉瘤多药耐药细胞株具有治疗作用。与单独使用阿霉素相比，装载阿霉素的纳米颗粒也显示骨肉瘤细胞凋亡增加。载阿霉素的脂质修饰葡聚糖纳米粒对骨肉瘤细胞系显示出明显的抗增殖作用。这些发现可能为MDR骨肉瘤提供新的治疗选择。
Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the efficacy. Doxorubicin was loaded onto a lipid-modified dextran based polymeric nano-system. The effect of various concentrations of doxorubicin alone or nanoparticle loaded doxorubicin on KHOS, KHOSR2, U-2OS, and U-2OSR2 cells was analyzed. Effects on drug retention, immunofluorescence, Pgp expression, and induction of apoptosis were also analyzed. Dextran nanoparticles loaded with doxorubicin had a curative effect on multidrug resistant osteosarcoma cell lines by increasing the amount of drug accumulation in the nucleus via Pgp independent pathway. Nanoparticles loaded with doxorubicin also showed increased apoptosis in osteosarcoma cells as compared with doxorubicin alone. Lipid-modified dextran nanoparticles loaded with doxorubicin showed pronounced anti-proliferative effects against osteosarcoma cell lines. These findings may lead to new treatment options for MDR osteosarcoma.
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影响因子：
10.3
作者：
BERNSTEIN, A;HURWITZ, E;WILCHEK, M
通讯作者：
WILCHEK, M
影响因子：
5.3
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影响因子：
5.5
作者：
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通讯作者：
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影响因子：
45.3
作者：
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通讯作者：
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