PEGylated squalenoyl-gemcitabine nanoparticles for the treatment of glioblastoma.
PEGylated squalenoyl-gemcitabine nanoparticles for the treatment of glioblastoma.
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DOI：
10.1016/j.biomaterials.2016.07.037
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发表时间：
2016-10
期刊：
影响因子：
14
通讯作者：
Saltzman, W. Mark
中科院分区：
文献类型：
--
作者：
Gaudin, Alice;Song, Eric;King, Amanda R.;Saucier-Sawyer, Jennifer K.;Bindra, Ranjit;Desmaele, Didier;Couvreur, Patrick;Saltzman, W. Mark
多形性胶质母细胞瘤（GBM）的新治疗是迫切需要的，因为GBM预后仍然很差，主要是由于治疗抗性、治疗剂在肿瘤组织中的不良分布以及化疗药物在脑细胞外空间中的快速代谢。纳米颗粒（NP）的对流增强递送（CED）已被证明可改善化疗药物向肿瘤床的递送，提供持续释放，并提高患有颅内肿瘤的动物的存活率。在这里，我们使用CED在基于角鲨烯的NP内施用吉西他滨（一种用作多种颅外实体瘤的一线治疗的核苷类似物），以克服GBM治疗的上述挑战。通过CED给药后，小百分比的聚乙二醇（PEG）显著增强了角鲨烯-吉西他滨纳米颗粒（SQ-Gem NPs）在健康动物和荷瘤动物中的分布。当在GBM的原位模型中进行测试时，SQ-Gem-PEG NP与游离吉西他滨相比，作为化疗药物和放射增敏剂，显示出显著改善的治疗功效。此外，将MR造影剂掺入SQ-Gem NP制剂中，提供了一种在输注期间非侵入性跟踪NP的方法。
New treatments for glioblastoma multiforme (GBM) are desperately needed, as GBM prognosis remains poor, mainly due to treatment resistance, poor distribution of therapeutics in the tumor tissue, and fast metabolism of chemotherapeutic drugs in the brain extracellular space. Convection-enhanced delivery (CED) of nanoparticles (NPs) has been shown to improve the delivery of chemotherapeutic drugs to the tumor bed, providing sustained release, and enhancing survival of animals with intracranial tumors. Here we administered gemcitabine, a nucleoside analog used as a first line treatment for a wide variety of extracranial solid tumors, within squalene-based NPs using CED, to overcome the above-mentioned challenges of GBM treatment. Small percentages of poly(ethylene) glycol (PEG) dramatically enhanced the distribution of squalene-gemcitabine nanoparticles (SQ-Gem NPs) in healthy animals and tumor-bearing animals after administration by CED. When tested in an orthotopic model of GBM, SQ-Gem-PEG NPs demonstrated significantly improved therapeutic efficacy compared to free gemcitabine, both as a chemotherapeutic drug and as a radiosensitizer. Furthermore, MR contrast agents were incorporated into the SQ-Gem NP formulation, providing a way to non-invasively track the NPs during infusion.
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影响因子：
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Ishida, T;Ichihara, M;Kiwada, H
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