Engineered nanoparticles interacting with cells: size matters

Abstract

With the rapid advancement of nanoscience and nanotechnology, detailed knowledge of interactions between engineered nanomaterials and cells, tissues and organisms has become increasingly important, especially in regard to possible hazards to human health. This review intends to give an overview of current research on nano-bio interactions, with a focus on the effects of NP size on their interactions with live cells. We summarize common techniques to characterize NP size, highlight recent work on the impact of NP size on active and passive cellular internalization and intracellular localization. Cytotoxic effects are also discussed.

Figure 1

Nanoparticle uptake. NPs may enter the human body via inhalation, ingestion or through the skin. In the extracellular fluid, NPs are coated by proteins and other biomolecules. The so-called protein corona determines how the NP interacts with a cell. Cellular internalization may involve active (receptor-mediated) or passive transport across the cell membrane.

Figure 2

Active NP uptake. (a – d) Internalization of DPA-QDs (8 nm) by HeLa cells [60]. (e – h) Uptake of DHLA-AuNCs (3.3 nm) by HeLa cells [61]. (i – l) Uptake of polystyrene NPs (100 nm, coated with carboxylic groups) by mesenchymal stem cells (MSCs) [63]. Reproduced with permission from the American Chemical Society and the Royal Chemical Society.

Figure 3

Passive NP uptake by red blood cells. (a – d) Internalization of DPA-QDs (8 nm) [77]. (e – l) Scanning electron micrographs (SEM) of RBCs (5% hematocrit) incubated with 100 μg mL^–1 of (e – h) small (~100 nm) and (i – l) large (~600 nm) mesoporous silica particles (MSN) [79]. Reproduced with permission from the American Chemical Society.

Figure 4

Cytotoxic effects of NPs. In the biological environment, NPs may trigger the production of reactive oxygen species (ROS). Elevated ROS levels may lead to (i) activation of cellular stress-dependent signaling pathways, (ii) direct damage of subcellular organelles such as mitochondria and (iii) DNA fragmentation in the nucleus, resulting in cell cycle arrest, apoptosis, and inflammatory response. NPs may interact with membrane-bound cellular receptors, e.g., growth factor (GF) receptors and integrins, inducing cellular phenotypes such as proliferation, apoptosis, differentiation, and migration. After internalization via endocytic pathways, NPs are trafficked along the endolysosomal network within vesicles with the help of motor proteins and cytoskeletal structures. To access cytoplasmic or nuclear targets, NPs must escape from the endolysosomal network and traverse through the crowded cytoplasm.