Effect of shape, size, and aspect ratio on nanoparticle penetration and distribution inside solid tissues using 3D spheroid models.
Effect of shape, size, and aspect ratio on nanoparticle penetration and distribution inside solid tissues using 3D spheroid models.
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DOI：
10.1002/adhm.201500441
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发表时间：
2015-10-28
影响因子：
10
通讯作者：
Roy, Krishnendu
中科院分区：
文献类型：
--
作者：
Agarwal, Rachit;Jurney, Patrick;Raythatha, Mansi;Singh, Vikramjit;Sreenivasan, Sidlgata. V.;Shi, Li;Roy, Krishnendu
纳米粒子（NP）在实体组织和肿瘤内的有效渗透和均匀分布对于其治疗和诊断的成功至关重要。虽然许多研究报道了纳米粒子大小和电荷对组织内分布的影响，但形状和纵横比对纳米粒子在实体组织内运输的作用仍不清楚。本文报道了喷射和闪光压印光刻技术制造的基于聚乙二醇的阴离子纳米水凝胶的纳米级几何形状如何影响其在 3D 球体（代表实体肿瘤样组织的血管间区域的模型）内的渗透和分布的实验和理论研究。出乎意料的是，与纳米棒或相同形状的较小纳米颗粒相比，低纵横比圆柱形纳米颗粒（H/D ≈0.3；盘状颗粒，高度为100 nm，直径为325 nm）显示出最大的组织内输送（输送的总货物量增加>50%）和更均匀的渗透。这与球形纳米颗粒相反，球形纳米颗粒尺寸越小，渗透越深、越均匀。我们的研究结果提供了关于固体组织内纳米粒子运输的基本新知识，并进一步确立了形状和纵横比作为开发更有效、更好渗透的药物或造影剂输送纳米载体的重要设计参数。
Efficient penetration and uniform distribution of nanoparticles (NPs) inside solid tissues and tumors is paramount to their therapeutic and diagnostic success. While many studies have reported the effect of NP size and charge on intratissue distribution, role of shape, and aspect ratio on NP transport inside solid tissues remain unclear. Here experimental and theoretical studies are reported on how nanoscale geometry of Jet and Flash Imprint Lithography-fabricated, polyethylene-glycol-based anionic nanohydrogels affect their penetration and distribution inside 3D spheroids, a model representing the intervascular region of solid, tumor-like tissues. Unexpectedly, low aspect ratio cylindrical NPs (H/D ≈0.3; disk-like particles, 100 nm height, and 325 nm diameter) show maximal intratissue delivery (>50% increase in total cargo delivered) and more uniform penetration compared to nanorods or smaller NPs of the same shape. This is in contrast to spherical NPs where smaller NP size resulted in deeper, more uniform penetration. Our results provide fundamental new knowledge on NP transport inside solid tissues and further establish shape and aspect ratio as important design parameters in developing more efficient, better penetrating, nanocarriers for drug, or contrast-agent delivery.
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