Decreased circulation time offsets increased efficacy of PEGylated nanocarriers targeting folate receptors of glioma
Decreased circulation time offsets increased efficacy of PEGylated nanocarriers targeting folate receptors of glioma
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DOI：
10.1088/0957-4484/18/38/385101
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发表时间：
2007-09-26
期刊：
影响因子：
3.5
通讯作者：
Bellamkonda, Ravi V.
中科院分区：
文献类型：
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作者：
McNeeley, Kathleen M.;Annapragada, Ananth;Bellamkonda, Ravi V.
脂质体和其他基于纳米载体的药物递送载体可以通过被动和/或主动靶向定位到肿瘤。被动靶向脂质体纳米载体通过增强的渗透性和保留（EPR）效应经由“渗漏”脉管系统在肿瘤中积累。被动蓄积取决于循环时间和肿瘤血管“渗漏”的程度。渗出后，主动靶向脂质体纳米载体通过受体介导的吸收有效地递送其有效负载。然而，由于网状内皮系统的识别和清除，靶向部分的掺入可损害血液中的循环时间，从而减少被动积累。在这里，我们比较了被动靶向阿霉素负载的聚乙二醇化脂质体纳米载体的有效性，主动靶向脂质体纳米载体在大鼠9 L脑肿瘤模型。尽管与PEG化脂质体纳米载体相比，叶酸受体（FR）靶向脂质体纳米载体显著缩短了血液循环时间;但两种治疗在给药后20和50 h的肿瘤内药物浓度相等。与未处理的对照相比，两种处理均使肿瘤接种的动物存活率显著增加60-80%，但在FR靶向和被动靶向纳米载体之间未观察到存活率差异。因此，允许主动靶向而不损害循环时间的替代方法对于充分实现受体介导的胶质瘤主动靶向的益处可能是重要的。
Liposomal and other nanocarrier based drug delivery vehicles can localize to tumours through passive and/ or active targeting. Passively targeted liposomal nanocarriers accumulate in tumours via ' leaky' vasculature through the enhanced permeability and retention ( EPR) effect. Passive accumulation depends upon the circulation time and the degree of tumour vessel ' leakiness'. After extravasation, actively targeted liposomal nanocarriers efficiently deliver their payload by receptor-mediated uptake. However, incorporation of targeting moieties can compromise circulation time in the blood due to recognition and clearance by the reticuloendothelial system, decreasing passive accumulation. Here, we compare the efficacy of passively targeted doxorubicin-loaded PEGylated liposomal nanocarriers to that of actively targeted liposomal nanocarriers in a rat 9L brain tumour model. Although folate receptor ( FR)-targeted liposomal nanocarriers had significantly reduced blood circulation time compared to PEGylated liposomal nanocarriers; intratumoural drug concentrations both at 20 and 50 h after administration were equal for both treatments. Both treatments significantly increased tumour inoculated animal survival by 60-80% compared to non-treated controls, but no difference in survival was observed between FR-targeted and passively targeted nanocarriers. Therefore, alternate approaches allowing for active targeting without compromising circulation time may be important for fully realizing the benefits of receptor-mediated active targeting of gliomas.