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1, 3β-葡聚糖锚定、紫杉醇负载壳聚糖纳米载体赋予增强的血液相容性和高效的抗神经胶质瘤干细胞治疗效果。

1, 3β-Glucan anchored, paclitaxel loaded chitosan nanocarrier endows enhanced hemocompatibility with efficient anti-glioblastoma stem cells therapy.

机构信息

Institute of Nano Science and Technology, Mohali, Punjab, India.

Institute of Nano Science and Technology, Mohali, Punjab, India.

出版信息

Carbohydr Polym. 2018 Jan 15;180:365-375. doi: 10.1016/j.carbpol.2017.10.030. Epub 2017 Oct 12.

DOI:10.1016/j.carbpol.2017.10.030
PMID:29103516
Abstract

Recurrence of glioblastoma is one of the major concerns due to its heterogeneous nature and association of Glioma Initiating stem-like Cells (GICs). Nanoparticles mediated delivery of chemotherapeutic agent targeting both cancer and glioma stem cells could provide a solution to recurrent malignancies of the glioblastoma tumor. The approach described here provides enhanced chemotherapeutic potency utilizing 1,3β-Glucan as an outer shell to the chitosan nanoparticles (Cs-NPs) loaded with paclitaxel to prevent hemolysis with, the core-shell nano-structure (Cs-PTX-NP) enabling effective chemotherapy against malignant glioblastoma. The prepared nanoparticles (1,3β-Cs-PTX-NPs) with sustained release of the paclitaxel provide a targeted therapeutic approach that overcome systemic toxicities with the 1,3β-Glucan shell and improve drug bioavailability. Hemolysis investigation indicated that 1,3β-Cs-PTX-NP was significantly less hemolytic than paclitaxel enabling intravenous delivery. Also, 1,3β-Cs-PTX-NPs were considerably more cytotoxic (IC50) against glioma cancer LN18 cells and C6 stem-like cells compared with the PTX. In conclusion, this study found that 1,3β-Cs-PTX-NP addressed serious limitation with systemic delivery of paclitaxel by preventing hemolysis and providing chemotherapeutic delivery with significant anti-cancer efficacy against recurrent glioblastoma.

摘要

由于其异质性和胶质瘤起始干细胞样细胞(GICs)的关联,复发性脑胶质瘤是主要关注点之一。针对癌症和神经胶质瘤干细胞的纳米颗粒介导的化疗药物传递,可能为复发性脑胶质瘤肿瘤的恶性肿瘤提供解决方案。这里描述的方法利用 1,3β-葡聚糖作为壳聚糖纳米颗粒(Cs-NPs)的外壳,负载紫杉醇,以防止溶血,具有核壳纳米结构(Cs-PTX-NP),从而对恶性神经胶质瘤提供有效的化疗。具有紫杉醇持续释放的制备的纳米颗粒(1,3β-Cs-PTX-NPs)提供了一种靶向治疗方法,该方法克服了 1,3β-葡聚糖壳的全身毒性并提高了药物的生物利用度。溶血研究表明,与紫杉醇相比,1,3β-Cs-PTX-NP 的溶血作用明显较小,从而可以进行静脉内给药。此外,与 PTX 相比,1,3β-Cs-PTX-NP 对神经胶质瘤 LN18 细胞和 C6 干细胞的细胞毒性(IC50)要强得多。总之,这项研究发现,1,3β-Cs-PTX-NP 通过防止溶血并提供具有显著抗癌功效的化学疗法来解决紫杉醇全身递送的严重局限性,从而针对复发性脑胶质瘤。

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