The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles

Abstract

Many types of nanoparticles (NPs) are tested for use in medical products, particularly in imaging and gene and drug delivery. For these applications, cellular uptake is usually a prerequisite and is governed in addition to size by surface characteristics such as hydrophobicity and charge. Although positive charge appears to improve the efficacy of imaging, gene transfer, and drug delivery, a higher cytotoxicity of such constructs has been reported. This review summarizes findings on the role of surface charge on cytotoxicity in general, action on specific cellular targets, modes of toxic action, cellular uptake, and intracellular localization of NPs. Effects of serum and intercell type differences are addressed. Cationic NPs cause more pronounced disruption of plasma-membrane integrity, stronger mitochondrial and lysosomal damage, and a higher number of autophagosomes than anionic NPs. In general, nonphagocytic cells ingest cationic NPs to a higher extent, but charge density and hydrophobicity are equally important; phagocytic cells preferentially take up anionic NPs. Cells do not use different uptake routes for cationic and anionic NPs, but high uptake rates are usually linked to greater biological effects. The different uptake preferences of phagocytic and nonphagocytic cells for cationic and anionic NPs may influence the efficacy and selectivity of NPs for drug delivery and imaging.

MiR-29a Assists in Preventing the Activation of Human Stellate Cells and Promotes Recovery From Liver Fibrosis in Mice

“…31,32 Surface charge is important for cellular uptake of nanoparticles, and positively charged nanoparticles show higher cell uptake than negatively charged particles. 33 We confirmed the presence of pharmacodynamics in miR-29a in mouse liver model using atelocollagen. We surmised that miR-29a reached the liver in the early phase of treatment (Figure 5a).…”

Nanoparticle–membrane interactions

“…There are also other important NP characteristics that can be experimentally controlled and which can influence the NP-membrane adhesion beside the size. Cationic NPs, for example, are often cytotoxic due to their attractive interaction with negatively charged membranes that leads to their rapid internalisation [66,67]. On the other hand, anionic NPs are generally less cytotoxic but they can easily undergo protein fouling when exposed to biological media.…”

Neurotoxicity of pre-incubated alpha-synuclein with neutral nanoliposomes on PC12 and SHSY5Y cell lines

“…Therefore, there is an essential requisite to assess the toxicity of nanoparticles before applying them as safe components in medical and pharmaceutical industries. The cytotoxicity of nanoparticles is mainly associated with particle parameters containing size, shape, chemical composition (purity, electronic properties, or crystallinity), surface structure (surface coatings-inorganic or organic), charge, hydrophobicity, and aggregation behavior [51,52]. Nevertheless, biological factors, including type of cells, and culture circumstances, such as temperature, culture medium components and cell density, can a ect cytotoxicity [52].…”