Simovic Spomenka, Song Yunmei, Nann Thomas, Desai Tejal A
Ian Wark Research Institute, University of South Australia, Mawson Lakes SA, Australia.
Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, City East Campus, Reid Building, Adelaide SA, Australia.
Nanomedicine. 2015 Jul;11(5):1169-78. doi: 10.1016/j.nano.2015.02.016. Epub 2015 Mar 16.
Characterization of intestinal absorption of nanoparticles is critical in the design of noninvasive anticancer, protein-based, and gene nanoparticle-based therapeutics. Here we demonstrate a general approach for the characterization of the intestinal absorption of nanoparticles and for understanding the mechanisms active in their processing within healthy intestinal cells. It is generally accepted that the cellular processing represents a major drawback of current nanoparticle-based therapeutic systems. In particular, endolysosomal trafficking causes degradation of therapeutic molecules such as proteins, lipids, acid-sensitive anticancer drugs, and genes. To date, investigations into nanoparticle processing within intestinal cells have studied mass transport through Caco-2 cells or everted rat intestinal sac models. We developed an approach to visualize directly the mechanisms of nanoparticle processing within intestinal tissue. These results clearly identify a mechanism by which healthy intestinal cells process nanoparticles and point to the possible use of this approach in the design of noninvasive nanoparticle-based therapies.
Advances in nanomedicine have resulted in the development of new therapies for various diseases. Intestinal route of administration remains the easiest and most natural. The authors here designed experiments to explore and characterize the process of nanoparticle transport across the intestinal tissue. In so doing, further insights were gained for future drug design.
纳米颗粒肠道吸收的特性对于非侵入性抗癌、基于蛋白质和基于基因的纳米颗粒疗法的设计至关重要。在此,我们展示了一种用于表征纳米颗粒肠道吸收以及理解其在健康肠道细胞内加工过程中起作用机制的通用方法。人们普遍认为细胞加工是当前基于纳米颗粒的治疗系统的一个主要缺点。特别是,内溶酶体运输会导致蛋白质、脂质、酸敏性抗癌药物和基因等治疗分子降解。迄今为止,对肠道细胞内纳米颗粒加工的研究是通过Caco-2细胞或外翻大鼠肠囊模型来研究物质运输。我们开发了一种直接可视化肠道组织内纳米颗粒加工机制的方法。这些结果清楚地确定了健康肠道细胞加工纳米颗粒的一种机制,并指出了这种方法在基于纳米颗粒的非侵入性疗法设计中的可能用途。
纳米医学的进展导致了针对各种疾病的新疗法的开发。肠道给药途径仍然是最简单和最自然的。本文作者设计实验来探索和表征纳米颗粒跨肠道组织运输的过程。这样做,为未来的药物设计获得了进一步的见解。