Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma.

Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma.
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阿霉素和长春新碱的双重修饰脂质体共递送可提高神经胶质瘤的靶向和治疗效果。

DOI:
10.1080/10717544.2017.1344334
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发表时间:
2017-11
期刊:
影响因子:
6
通讯作者:
Mei X
Mei X
中科院分区:
医学2区
文献类型:
--
作者:
Zhang Y;Zhai M;Chen Z;Han X;Yu F;Li Z;Xie X;Han C;Yu L;Yang Y;Mei X

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由于耐药性和药物穿过多种生理屏障(包括血脑屏障(BBB)和血肿瘤屏障(BTB))的低渗透性,用于治疗胶质瘤的治疗结果通常是有限的。为了克服这些障碍,我们设计了T7和DA 7 R双肽修饰的脂质体(简称T7/DA 7 R-LS),以有效地将阿霉素(DOX)和长春新碱(VCR)共递送到胶质瘤中。T7是转铁蛋白受体(transferrin receptor,TfR)的七肽配体,能够绕过血脑屏障,靶向胶质瘤。DA 7 R是血管内皮生长因子受体2(VEGFR 2)的d肽配体,其在血管生成中过表达,表现出优异的胶质瘤归巢特性。通过结合双靶向递送效应,双修饰脂质体显示出比单配体修饰脂质体或游离药物更高的胶质瘤定位。T7/DA 7 R-LS负载DOX和VCR后,体内抗胶质瘤效果最好。总之,这种双靶向共递送策略为改善脑药物递送和抗胶质瘤治疗效果提供了潜在的方法。
Therapeutic outcome for the treatment of glioma was often limited due to drug resistance and low permeability of drug across the multiple physiological barriers, including the blood-brain barrier (BBB), and the blood-tumor barrier (BTB). In order to overcome these hurdles, we designed T7 and DA7R dual peptides-modified liposomes (abbreviated as T7/DA7R-LS) to efficiently co-delivery doxorubicin (DOX) and vincristine (VCR) to glioma in this study. T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma. DA7R is a d-peptide ligand of vascular endothelial growth factor receptor 2 (VEGFR 2) overexpressed on angiogenesis, presenting excellent glioma-homing property. By combining the dual-targeting delivery effect, the dual-modified liposomes displayed higher glioma localization than that of single ligand-modified liposomes or free drug. After loading with DOX and VCR, T7/DA7R-LS showed the most favorable antiglioma effect in vivo. In conclusion, this dual-targeting, co-delivery strategy provides a potential method for improving brain drug delivery and antiglioma treatment efficacy.
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