Mechanistic understanding of nanoparticles' interactions with extracellular matrix: the cell and immune system

Abstract

Extracellular matrix (ECM) is an extraordinarily complex and unique meshwork composed of structural proteins and glycosaminoglycans. The ECM provides essential physical scaffolding for the cellular constituents, as well as contributes to crucial biochemical signaling. Importantly, ECM is an indispensable part of all biological barriers and substantially modulates the interchange of the nanotechnology products through these barriers. The interactions of the ECM with nanoparticles (NPs) depend on the morphological characteristics of intercellular matrix and on the physical characteristics of the NPs and may be either deleterious or beneficial. Importantly, an altered expression of ECM molecules ultimately affects all biological processes including inflammation. This review critically discusses the specific behavior of NPs that are within the ECM domain, and passing through the biological barriers. Furthermore, regenerative and toxicological aspects of nanomaterials are debated in terms of the immune cells-NPs interactions.

Keywords: Biological barriers; Extracellular matrix; Inflammation; Nanoparticle.

Fig. 1

Classification of ECM molecules

Fig. 2

Components of ECM

Fig. 3

Schematic presentation of localization of basic ECM structures

Fig. 4

Anti-Gal antibody/ alpha-gal liposome interaction promotes wound healing by recruiting and activating macrophages

Fig. 5

Effect of metal NPs and hyaluronan oligomers on the elastic fiber formation in the ECM. Initially, the tropoelastin molecule is secreted from the cell and binds to the elastin binding protein (EBP) on the cell membrane. Tropoelastin deposition and crosslinking by LOX on the glycoprotein microfibrils form mature tropoelastin fibers. (ROS: reactive oxygen species, MMP: matrix metalloproteinase, TIMP: tissue inhibitors of matrix proteases, IL-1beta: interleukin-1beta, TGF-beta: transforming growth factor beta, BMP-1: Bone morphogenetic protein-1/Tolloid metalloproteinase, PI3Kinase: Phosphoinositide 3-kinase, LOX: Lysyl oxidase)

Fig. 6

Transport mechanisms within tissue. Small molecules can be transported either transcellularly or paracellularly, while macromolecules and NPs use transcytosis [121]

Fig. 7

Endothelial cell interaction with ECM. Barrier function is maintained by endothelial cells inter-cellular interactions and adherence to ECM. Occludin, claudins, and junctional adhesion molecules (JAMs) comprise the tight junctions, while VE-cadherin interactions stabilize adherens junctions. Connexins develop gap junctions. Junctional stability is intracellularly maintained by linking with the actin cytoskeleton intermediated by catenins (e,g, β-catenin, α-catenin; γ-catenin;) or zona occluden-1 protein. Endothelial cells interact with ECM matrix protein (fibronectin or vitronectin) through integrin receptors. Proteins like talin and vinculin link integrins’ cytosolic domains with actin cytoskeleton, these proteins are also involved in integrin-mediated signaling

Fig. 8

Drug-loaded G5-N-Acetylgalactosamine (NAcGal) conjugate that can bind to the asialoglycoprotein receptor (ASGPR) expressed on the surface of hepatic cancer cells. Binding of the drug-loaded conjugate to ASGPR triggers receptor-mediated endocytosis followed by endosomal escape and release of the drug, ASPGR recycles to be again expressed on the cell’s surface