Transferrin Adsorption onto PLGA Nanoparticles Governs Their Interaction with Biological Systems from Blood Circulation to Brain Cancer Cells
Transferrin Adsorption onto PLGA Nanoparticles Governs Their Interaction with Biological Systems from Blood Circulation to Brain Cancer Cells
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DOI：
10.1007/s11095-011-0624-1
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发表时间：
2012-06-01
影响因子：
3.7
通讯作者：
Garcion, Emmanuel
中科院分区：
文献类型：
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作者：
Chang, Jiang;Paillard, Archibald;Garcion, Emmanuel
纳米药物代表了治疗侵袭性胶质母细胞瘤的替代方案。这里研究了PLGA-纳米颗粒（NPs）的行为，作为它们在它们预期要面对的不同生物界面处的蛋白质吸附特性的函数，以到达脑癌细胞。在健康大鼠脑和脑肿瘤内的内吞行为和积累。通过牛血清白蛋白（BSA）或转铁蛋白（Tf）对PLGA-NP进行蛋白质包被（80至90 nm）和ζ电位（-44至-32 mV），当静脉内注射到大鼠和小鼠中时，大大延长了它们的血液半衰期。与THP-1单核细胞相反，分化的THP-1巨噬细胞、F98胶质瘤细胞和星形胶质细胞内化BSA-和Tf-纳米颗粒。通过小窝和网格蛋白介导的途径增加F98细胞对Tf-NP的摄取支持Tf和过表达的Tf受体之间的特异性相互作用。最后，发现Tf-NPs对健康大脑的靶向作用高于BSA-NPs，而两种NPs均大量进入脑发育的肿瘤中，这些数据共同证明Tf-NPs代表了一种有趣的纳米药物，可在肿瘤早期和晚期通过全身或局部策略将抗癌药物递送至胶质瘤细胞。
Nanomedicines represent an alternative for the treatment of aggressive glioblastoma tumors. Behaviour of PLGA-nanoparticles (NPs) was here investigated as a function of their protein adsorption characteristics at the different biological interfaces they are expected to face in order to reach brain cancer cells.NPs were studied for size, zeta potential, blood half-life, endocytic behavior and accumulation within healthy rat brain and brain tumors.While slightly modifying size (80 to 90 nm) and zeta potential (-44 to -32 mV) protein coating of PLGA-NPs by bovine serum albumin (BSA) or transferrin (Tf) greatly prolonged their blood half-life when intravenously injected in rats and mice. In contrast with THP-1 monocytes, differentiated THP-1 macrophages, F98 glioma cells and astrocytes internalized BSA- and Tf-NPs . Increase of Tf-NP uptake by F98 cells through caveolae- and clathrin-mediated pathways supports specific interaction between Tf and overexpressed Tf-receptor. Finally, targeting of healthy brain was found higher with Tf-NPs than with BSA-NPs while both NPs entered massively within brain-developed tumors.Taken together, those data evidence that Tf-NPs represent an interesting nanomedicine to deliver anticancer drugs to glioma cells through systemic or locoregional strategies at early and late tumor stages.