Brain-penetrating nanoparticles improve paclitaxel efficacy in malignant glioma following local administration.
Brain-penetrating nanoparticles improve paclitaxel efficacy in malignant glioma following local administration.
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DOI：
10.1021/nn504210g
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发表时间：
2014-10-28
期刊：
影响因子：
17.1
通讯作者：
Hanes, Justin
中科院分区：
文献类型：
--
作者：
Nance, Elizabeth;Zhang, Clark;Shih, Ting-Yu;Xu, Qingguo;Schuster, Benjamin S.;Hanes, Justin
肿瘤内药物分布差和药物半衰期短严重限制了化疗在大多数癌症（包括原发性脑肿瘤）中的疗效。通过控释聚合物的局部或靶向药物递送是治疗浸润性脑肿瘤的一种有前途的策略，这种肿瘤不能通过手术完全切除。然而，传统的局部疗法限制了药物的渗透，因为小分子药物经常进入它们遇到的第一个细胞，并且仅从给药部位行进很短的距离。避免与肿瘤细胞外基质的粘附相互作用的纳米颗粒可以改善药物分布并在应用于肿瘤区域时维持药物释放。我们之前已经表明，直径高达114 nm的模型聚苯乙烯纳米颗粒能够在正常脑组织中快速扩散，但只有在涂覆有异常致密的聚乙二醇（PEG）层以减少粘附相互作用的情况下。在这里，我们证明，紫杉醇（PTX）负载，聚（乳酸-共-乙醇酸）（PLGA）-co-PEG嵌段共聚物纳米粒子的平均直径为70 nm的扩散速度比类似大小的PTX负载PLGA颗粒（无PEG涂层）快100倍。与载有PTX的PLGA纳米颗粒或未包封的PTX相比，载有密集PEG化PTX的纳米颗粒在局部给药于已建立的脑肿瘤后显著延迟肿瘤生长。延迟的肿瘤生长与载药的PLGA-PEG纳米颗粒向肿瘤浸润前沿的增强分布相结合证明了颗粒在脑肿瘤实质内的渗透提高了治疗功效。使用载药的脑穿透纳米颗粒是一种很有前途的方法，以实现持续和更均匀的药物输送，以治疗侵袭性胶质瘤和潜在的其他脑部疾病。
Poor drug distribution and short drug half-life within tumors strongly limit efficacy of chemotherapies in most cancers, including primary brain tumors. Local or targeted drug delivery via controlled-release polymers is a promising strategy to treat infiltrative brain tumors, which cannot be completely removed surgically. However, drug penetration is limited with conventional local therapies since small-molecule drugs often enter the first cell they encounter and travel only short distances from the site of administration. Nanoparticles that avoid adhesive interactions with the tumor extracellular matrix may improve drug distribution and sustain drug release when applied to the tumor area. We have previously shown model polystyrene nanoparticles up to 114 nm in diameter were able to rapidly diffuse in normal brain tissue, but only if coated with an exceptionally dense layer of poly(ethylene glycol) (PEG) to reduce adhesive interactions. Here, we demonstrate that paclitaxel (PTX)-loaded, poly(lactic-co-glycolic acid) (PLGA)-co-PEG block copolymer nanoparticles with an average diameter of 70 nm were able to diffuse 100-fold faster than similarly sized PTX-loaded PLGA particles (without PEG coatings). Densely PEGylated PTX-loaded nanoparticles significantly delayed tumor growth following local administration to established brain tumors, as compared to PTX-loaded PLGA nanoparticles or unencapsulated PTX. Delayed tumor growth combined with enhanced distribution of drug-loaded PLGA-PEG nanoparticles to the tumor infiltrative front demonstrates that particle penetration within the brain tumor parenchyma improves therapeutic efficacy. The use of drug-loaded brain-penetrating nanoparticles is a promising approach to achieve sustained and more uniform drug delivery to treat aggressive gliomas and potentially other brain disorders.
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影响因子：
15.9
作者：
Inoue, Tomoo;Yamashita, Yoji;Tominaga, Teiji
通讯作者：
Tominaga, Teiji
影响因子：
4.1
作者：
Degen, JW;Walbridge, S;Lonser, RR
通讯作者：
Lonser, RR
影响因子：
15.9
作者：
Krauze, Michal T.;Noble, Charles O.;Bankiewicz, Krystof S.
通讯作者：
Bankiewicz, Krystof S.
影响因子：
1.9
作者：
Lopez, Kim A.;Waziri, Allen E.;Bruce, Jeffrey N.
通讯作者：
Bruce, Jeffrey N.
DOI：
10.1073/pnas.0604318103
发表时间：
2006-08-01
影响因子：
11.1
作者：
Kinoshita, Manabu;McDannold, Nathan;Hynynen, Kullervo
通讯作者：
Hynynen, Kullervo