In Vivo Distribution of Polymeric Nanoparticles at the Whole-Body, Tumor, and Cellular Levels
In Vivo Distribution of Polymeric Nanoparticles at the Whole-Body, Tumor, and Cellular Levels
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DOI：
10.1007/s11095-010-0068-z
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发表时间：
2010-11-01
影响因子：
3.7
通讯作者：
Allen, Christine
中科院分区：
文献类型：
--
作者：
Lee, Helen;Hoang, Bryan;Allen, Christine
嵌段共聚物胶束 (BCM) 用铟-111 和/或表皮生长因子 (EGF) 进行功能化，从而能够研究被动和主动靶向 BCM 的体内转运。传统技术和基于图像的技术的整合提供了新的定量方法，以深入了解聚合物纳米粒子在体内的命运。在携带人乳腺异种移植物的无胸腺小鼠中进行药代动力学和生物分布研究，以评估 NT-BCM（非靶向，EGF-）和 T-BCM（靶向，EGF+）的全身转运。使用 MicroSPECT/CT 和放射自显影成像研究 BCM 的瘤内分布，并辅以定量 MATLABA (R) 分析。通过伽玛计数对肿瘤进行分级，以量化 BCM 的细胞内摄取。NT-BCM 和 T-BCM 的肿瘤内分布被发现是异质的，并且与肿瘤血管化呈正相关（r > 0.68 +/- 0.04）。研究发现，T-BCM 体内细胞摄取和细胞膜结合的增强延迟了其从过度表达 EGFR 的肿瘤中的清除，因此与 NT-BCM 相比，导致 T-BCM 的肿瘤积累增强。为了实现有效的主动靶向，需要充分的被动靶向。肿瘤生理学对被动和主动靶向 BCM 的跨血管和瘤内转运具有重大影响。
Block copolymer micelles (BCMs) were functionalized with indium-111 and/or epidermal growth factor (EGF), which enabled investigation of the in vivo transport of passively and actively targeted BCMs. The integration of conventional and image-based techniques afforded novel quantitative means to achieve an in-depth insight into the fate of polymeric nanoparticles in vivo.Pharmacokinetics and biodistribution studies were performed in athymic mice bearing human breast xenografts to evaluate the whole-body transport of NT-BCMs (non-targeted, EGF-) and T-BCMs (targeted, EGF+). The intratumoral distribution of BCMs was investigated using MicroSPECT/CT and autoradiographic imaging, complemented with quantitative MATLABA (R) analyses. Tumors were fractionated for quantifying intracellular uptake of BCMs via gamma-counting.The intratumoral distribution of NT-BCMs and T-BCMs were found to be heterogeneous, and positively correlated with tumor vascularization (r > 0.68 +/- 0.04). The enhanced in vivo cell uptake and cell membrane binding of T-BCMs were found to delay their clearance from tumors overexpressing EGFR, and therefore resulted in enhanced tumor accumulation for the T-BCMs in comparison to the NT-BCMs.Adequate passive targeting is required in order to achieve effective active targeting. Tumor physiology has a significant impact on the transvascular and intratumoral transport of passively and actively targeted BCMs.