Surface engineered polymeric nanocarriers mediate the delivery of transferrin-methotrexate conjugates for an improved understanding of brain cancer
Surface engineered polymeric nanocarriers mediate the delivery of transferrin-methotrexate conjugates for an improved understanding of brain cancer
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DOI：
10.1016/j.actbio.2015.06.027
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发表时间：
2015-09-15
影响因子：
9.7
通讯作者：
Soni, Vandana
中科院分区：
文献类型：
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作者：
Jain, Atul;Jain, Ashay;Soni, Vandana
本研究的目的是增强生物活性分子通过聚山梨醇酯80（Polysorbate 80）包覆的聚乳酸-羟基乙酸共聚物（PLGA）纳米粒（NPs）与甲氨蝶呤-转铁蛋白（Tw-Mtx-Tf-NP）缀合物（Mtx-Tf）的渗透穿过血脑屏障（BBB）。通过Pluronic F-68和/或聚山梨酯80（Tween 80/Tw）确定了开发制剂通过内吞作用的易跨BBB迁移以及对脑中存在的P-gp外排泵的抑制。转铁蛋白（Tf）受体在癌细胞表面的过表达允许通过受体介导的内吞作用靶向和持续递送与脑癌细胞缀合的Mtx-Tf。与非靶向实验NP对照相比，开发的制剂显示出改善的渗透。通过静脉途径向白化病大鼠施用FITC标记的载药NP，进行了这种纳米级聚合物载体的转运潜力和生物分布研究，显示成功的迁移和跨BBB通道。我们已经在实验诱导的携带肿瘤的大鼠模型中验证了新配制的和载药的NP与对照相比的抗肿瘤效率。本研究表明，由于其在癌症治疗干预中的靶向和持续递送潜力，开发的制剂具有更大的相容性、更小的器官毒性和更高的抗肿瘤活性。总之，我们的研究结果的靶向和持续的药物输送潜力的纳米粒子在体外和体内的证据得到证实，并制定新的交付车辆显示其在开发新的工具，用于治疗脑癌的价值。(C)2015 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
The objective of present study was to enhance permeation of bioactive molecules across blood brain barrier (BBB) through polysorbate 80 coated poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with methotrexate-transferrin (Tw-Mtx-Tf-NP) conjugates (Mtx-Tf). The easy trans-BBB migration of developed formulations through endocytosis, and inhibition of P-gp efflux pump present in brain were established by Pluronic F-68 and/or polysorbate 80 (Tween 80/Tw). The over-expression of transferrin (Tf) receptors on cancer cell surface allowed targeted and sustained delivery of Mtx-Tf conjugated to brain cancer cells by receptor mediated endocytosis. The developed formulations showed improved penetration in comparison to non-targeting experimental NP controls. The transportation potential and bio-distribution studies of such nanosized polymeric carriers showing successful migration and trans-BBB passage was carried out by administering FITC labeled drug loaded NPs to albino rats through intravenous route. We have validated anti-tumor efficiency of newly formulated and drug loaded NPs compared to controls in experimentally induced tumor-harboring rat model. The present study suggests greater compatibility, less organ toxicity and higher anti-tumor activity of developed formulations due to their targeting and sustained delivery potential in cancer therapeutic interventions. In conclusion, our findings of targeted and sustained drug delivery potential of NPs for are corroborated with in vitro and in vivo evidence, and formulated novel delivery vehicle shows its value in developing new tools for treating brain cancer. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.