Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles.
Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles.
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DOI：
10.1016/j.jconrel.2013.09.013
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发表时间：
2013-12-28
期刊：
影响因子：
--
通讯作者：
Li SD
中科院分区：
文献类型：
--
作者：
Ernsting MJ;Murakami M;Roy A;Li SD
纳米颗粒向肿瘤的药物递送受到多种因素的影响：纳米颗粒必须逃避肾过滤和网状内皮系统的清除，通过肿瘤中扩大的内皮间隙渗出，穿透肿瘤微环境中的致密基质到达肿瘤细胞，在肿瘤组织中停留较长时间，并最终释放活性剂以诱导药理作用。纳米颗粒的物理化学性质，如尺寸、形状、表面电荷、表面化学（聚乙二醇化、配体缀合）和组成影响药代动力学、生物分布、肿瘤内渗透和肿瘤生物利用度。另一方面，肿瘤生物学（血流、灌注、渗透性、间质液压力和基质含量）和患者特征（年龄、性别、肿瘤类型、肿瘤位置、身体组成和先前治疗）也对纳米颗粒的药物递送有影响。现在认为，纳米颗粒和肿瘤微环境都必须优化或调整以实现最佳递送。本文综述了这些纳米颗粒和生物因素如何影响纳米颗粒向肿瘤的递送，并讨论了如何调整肿瘤微环境以及如何通过成像方法对患者进行分层以获得纳米医学的最大益处。展望和未来的方向也提供了。
Nanoparticle drug delivery to the tumor is impacted by multiple factors: nanoparticles must evade clearance by renal filtration and the reticuloendothelial system, extravasate through the enlarged endothelial gaps in tumors, penetrate through dense stroma in the tumor microenvironment to reach the tumor cells, remain in the tumor tissue for a prolonged period of time, and finally release the active agent to induce pharmacological effect. The physicochemical properties of nanoparticles such as size, shape, surface charge, surface chemistry (PEGylation, ligand conjugation) and composition affect the pharmacokinetics, biodistribution, intratumoral penetration and tumor bioavailability. On the other hand, tumor biology (blood flow, perfusion, permeability, interstitial fluid pressure and stroma content) and patient characteristics (age, gender, tumor type, tumor location, body composition and prior treatments) also have impact on drug delivery by nanoparticles. It is now believed that both nanoparticles and the tumor microenvironment have to be optimized or adjusted for optimal delivery. This review provides a comprehensive summary of how these nanoparticle and biological factors impact nanoparticle delivery to tumors, with discussion on how the tumor microenvironment can be adjusted and how patients can be stratified by imaging methods to receive the maximal benefit of nanomedicine. Perspectives and future directions are also provided.
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影响因子：
4.9
作者：
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通讯作者：
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DOI：
10.1073/pnas.241655998
发表时间：
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