Effect of Flow-Induced Shear Stress in Nanomaterial Uptake by Cells: Focus on Targeted Anti-Cancer Therapy

Abstract

Recently, nanomedicines have gained a great deal of attention in diverse biomedical applications, including anti-cancer therapy. Being different from normal tissue, the biophysical microenvironment of tumor cells and cancer cell mechanics should be considered for the development of nanostructures as anti-cancer agents. Throughout the last decades, many efforts devoted to investigating the distinct cancer environment and understanding the interactions between tumor cells and have been applied bio-nanomaterials. This review highlights the microenvironment of cancer cells and how it is different from that of healthy tissue. We gave special emphasis to the physiological shear stresses existing in the cancerous surroundings, since these stresses have a profound effect on cancer cell/nanoparticle interaction. Finally, this study reviews relevant examples of investigations aimed at clarifying the cellular nanoparticle uptake behavior under both static and dynamic conditions.

Keywords: anti-cancer; flow; in vitro; nanomedicine; nanoparticle; shear stress; targeted therapy.

Figure 1

Mechanism in which normal cells get their nutrients and excrete their wastes.

Figure 2

Shear stresses experienced by cells in solid tumor and circulating tumor cells.

Figure 3

A typical flow chamber setup. (A) depicts a closed-circuit chamber, in which the chamber is connected to a peristaltic pump and a reservoir (cell media). (B) illustrates the flow chamber assembly where coverslip containing the cells is allowed for fluid flow. Adapted from bioptechs [42].

Figure 4

Microfluidic devices as models in which they provide conditions similar to in-vivo animal models and in-vivo models still retaining the simplicity of in-vitro testing. Adapted from Björnmalm et al. [41].

Figure 5

Comparison between distributions of nanomaterials under static (A) and dynamic (B) conditions. In static culture, nanoparticles tend to sediment and aggregate due to their high surface energy. This condition create physiochemical stress on cells, which might alter cells viability as well as particles uptake On the other hand, in dynamic culture, the particles will be uniformly distributed allowing better cellular interaction, which can be charge-dependent as the direction of the negatively-charged particles will be away from the cell surface, unlike positively-charged particles, where the particle direction will be towards the cell surface. Adapted from Mahto et al. [43].

Figure 6

Filamentations or 2D nanomaterials align differently when there is fluid flow in cancer microenvironment. This flow-aligning effect can change the way that the cells interact with nanoparticles thus their cellular uptake would be influenced. Adapted from Björnmalm et al. [41].

Figure 7

Cell internalization pathways of particles with different elasticity. Soft NLP-45KPa (a) enters the cell via two pathways: fusion and endocytosis. Hard NLG-19MPa (b) enters cell via only endocytosis. Adapted from Guo et al. [50].