Agarwal Rachit, Jurney Patrick, Raythatha Mansi, Singh Vikramjit, Sreenivasan Sidlgata V, Shi Li, Roy Krishnendu
The Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Department of Mechanical EngineeringThe University of Texas at Austin, Austin, TX, 78712, USA.
Adv Healthc Mater. 2015 Oct 28;4(15):2269-80. doi: 10.1002/adhm.201500441. Epub 2015 Sep 16.
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.
纳米颗粒(NPs)在实体组织和肿瘤内部的高效渗透及均匀分布对其治疗和诊断的成功至关重要。虽然许多研究报道了NP大小和电荷对组织内分布的影响,但形状和纵横比对NP在实体组织内运输的作用仍不清楚。本文报道了关于喷射和闪光压印光刻制造的基于聚乙二醇的阴离子纳米水凝胶的纳米级几何结构如何影响其在三维球体(一种代表实体肿瘤样组织血管间区域的模型)内的渗透和分布的实验和理论研究。出乎意料的是,与相同形状的纳米棒或较小的NP相比,低纵横比的圆柱形NP(H/D≈0.3;盘状颗粒,高度100nm,直径325nm)显示出最大的组织内递送(总递送货物增加>50%)和更均匀的渗透。这与球形NP相反,在球形NP中,较小的NP尺寸导致更深、更均匀的渗透。我们的结果提供了关于NP在实体组织内运输的重要新知识,并进一步确立了形状和纵横比作为开发更高效、穿透性更好的用于药物或造影剂递送的纳米载体的重要设计参数。