Nanoparticles: Cellular Uptake and Cytotoxicity

Abstract

Understanding the interactions of nanoparticles (NPs) with cells and how these interactions influence their cellular uptake is essential to exploring the biomedical applications of NPs, particularly for drug delivery. Various factors, whether differences in physical properties of NPs or variations in cell-membrane characteristics, influence NP-cell interactions and uptake processes. NP-cell membrane interactions may also influence intracellular trafficking of NPs, their sorting into different intracellular compartments, cellular retention, and hence the efficacy of encapsulated therapeutics. A crucial consideration is whether such interactions might cause any toxicity, starting with how NPs interact in transit with the biological environment prior to their interactions with targeted cells and tissues. Understanding the effects of various NP characteristics on cellular and biological processes could help in designing NPs that are efficient but also nontoxic.

Uptake and bioconversion of stereoisomeric dipeptide prodrugs of ganciclovir by nanoparticulate carriers in corneal epithelial cells

“…The uptake of prodrug-loaded PLGA NP can be taken up by this predominant pathway of cellular internalization of NP without direct interaction of NP with the cell membrane, because the bulk extracellular fluid is internalized (Yameen et al, 2014;Adjei et al, 2014). However, NPs that interact with cell membranes enable higher uptake through this mechanism than NPs that do not (Adjei et al, 2014). During the process of cellular internalization of NP, surface energy may facilitate by lowering bending energy to induce curvature of the lipid bilayer.…”

Development of an iron quantification method using nuclear magnetic resonance relaxometry

“…15,21,[32][33][34] NMR offers an alternative method for iron quantification when using IONPs as MRI contrast agents, such as r 1 and r 2 relaxivity measurements. Here, an iron quantification method based on NMR relaxometry using a Bruker minispec (mq 60, 60 MHz, 1.4 T) was developed and compared with ICP analysis and ferrozine iron assays.…”

Aggregation is a critical cause of poor transfer into the brain tissue of intravenously administered cationic PAMAM dendrimer nanoparticles

“…In vitro studies carried out by us and others have demonstrated that cationic PAMAM dendrimer particles are rapidly captured by cultured cells and trapped within endosomal vesicles. 10,13 As PAMAM dendrimers are considered to have no counteracting antibodies, receptors, or transporter molecules on the cell surface, the main mechanism for BBB permeation of these particles would be adhesion-induced cellular pinocytosis and succeeding exocytosis, the so-called process of adhesive transcytosis. 22,23 In this study, we measured the in vitro BBB permeability of dendrimer nanoparticles, which revealed a permeability coefficient of 8.0×10…”

“…Owing to the cationic surface, amine-terminated PAMAM dendrimer particles tend to be easily adsorbed on to cell membranes and are consequently internalized promptly by the cells and trapped within endosomal vesicles, finally succumbing to lysosomal digestion. 10 However, PAMAM dendrimer particles have many tertiary amines within the particles, and these amines act as buffers against invasion by protons outside the lysosomes, aiding in their lysosomal escape, which process is called "proton sponge effect". 11,12 For all the merits of PAMAM dendrimer particles as nanocarriers to target cells, they have the disadvantage of exerting explicit cytotoxicity.…”