Cellular Uptake, Cytotoxicity, and Innate Immune Response of Silica−Titania Hollow Nanoparticles Based on Size and Surface Functionality

Abstract

Silica-titania hollow nanoparticles (HNPs) with uniform diameters of 25, 50, 75, 100, and 125 nm were fabricated by dissolution and redeposition method in order to evaluate size dependent cellular response. Surface-modified HNPs with cationic, anionic, and neutral functional group were prepared by silane treatment. We systematically investigated cellular internalization, toxicity, and innate immune response of HNPs in human breast cancer (SK-BR-3) and mouse alveolar macrophage (J774A.1) cells. Size- and surface functionality-dependent cellular uptake of HNPs was investigated by fluorescence labeling (fluorescein isothiocyanate), inductively coupled plasma-emission spectroscopy, and ultrastructural resolution using transmission electron microscopy. Viability, reactive oxygen species, and apoptosis/necrosis of HNP-treated J774A.1 revealed the size-dependent phenomenon. Innate immune response of HNP-treated macrophages was measured by three cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor α. Among the HNPs of different sizes, 50-nm HNPs demonstrated the highest toxic influence on macrophages. Among the HNPs with surface functionalities, cationic HNPs demonstrated the most toxic effect on J774A.1 and the highest uptake efficiency. The toxicity results of HNP-treated macrophages were consistent with the cellular internalization efficiency. These findings provide size- and surface functionality-dependent nanotoxicity and uptake of HNPs, and lead to HNPs for bioapplications such as drug delivery and imaging probe.

Gene expression profiles in primary duodenal chick cells following transfection with avian influenza virus H5 DNA plasmid encapsulated in silver nanoparticles

“…32 Induction of proinflammatory cytokines, such as IL-1, IL-6, and tumor necrosis factor, is also thought to be associated with cytotoxicity. 33 However, in the present study, no expression of IL-1 and IL-6 was found following inoculation of primary cells with naked plasmids (pIREGFP and pIREGFP-H5) or with AgNPs, AgNP-pIREGFP, or Lipo-pIREGFP.…”

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

“…Charged NPs, eg, gold particles, are more cytotoxic than neutral forms, 29 and positively charged ZnO, silica, silica-titania hollow, and gold nanoparticles act more cytotoxically than negative variants of similar size in nonphagocytic cells. [30][31][32][33][34] Cytotoxic action of poly(amidoamine) (PAMAM) dendrimers is correlated with the number of primary amino groups, 35 and cytotoxicity of PAMAM dendrimers decreased when amine groups were neutralized with acetyl groups. 36 Also, in in vivo experiments, high numbers of primary amine groups increased the toxicity of dendrimers.…”

Particle size- and number-dependent delivery to cells by layered double hydroxide nanoparticles

“…Of these characteristics, the particle size is a crucial factor which determines NP endocytosis pathway [17,18], uptake rate and efficiency [6,16,[19][20][21][22], in vitro cytotoxicity [23][24][25][26][27][28], immune responses [27][28][29][30], and the final localisation [15,31,32]. Thus size-dependent uptake of various NPs has been intensively investigated and widely reported.…”

“…This could be caused by several vague parameters without clear and consistent definition. The first one is NP size, which is normally characterised as the Z-average hydrodynamic diameter (measured by light scattering technology) [29,41,50] or the number average size (measured and statistically calculated from TEM or SEM images) [6,28]. The second term is the dose of nanoparticle.…”