Surface Modification of Stöber Silica Nanoparticles with Controlled Moiety Densities Determines Their Cytotoxicity Profiles in Macrophages

Abstract

Physicochemical properties of nanomaterials play important roles in determining their toxicological profiles during nano-biointeraction. Among them, surface modification is one of the most effective manners to tune the cytotoxicity induced by nanomaterials. However, currently, there is no consistency in surface modification including moiety types and quantities considering the conflicting toxicological profiles of particles across different studies. In this study, in order to systematically investigate how the moiety density affects cytotoxicity of NPs, we chose three different types of functional groups, that is, −NH2, −COOH, and −PEG, and further controlled their densities on modified Stöber silica nanoparticles (NPs). We demonstrated that densities of functional groups could significantly affect the cytotoxicities of Stöber silica NPs. Regardless of the types of functional groups, high grafting densities could ameliorate the cytotoxicities induced by Stöber silica NPs in macrophages, for example, J774A.1 and N9 cells. When equal amounts of functional groups were present, the cell viability increased in the order of −COOH < −NH2 < −PEG. Furthermore, it was shown that surface modification could significantly affect the quantities of the surface silanol, which is the determining factor that affects their cytotoxicity. These results show that it is critical to control the surface moiety both quantitatively and qualitatively, which can tune the interaction outcomes at the nano-bio interface. The results found in this article provide useful guidance to adjust nanomaterial cytotoxicity for safer biomedical applications.

Size and surface modification of silica nanoparticles affect the severity of lung toxicity by modulating endosomal ROS generation in macrophages

“…The exact mechanism of silica nanoparticleinduced cellular toxicity has not been elucidated. However, it is assumed that interaction of the silanol moiety of a particle surface with the cellular membrane and induction of ROS generation are involved [36,37]. Accordingly, we rst assessed intracellular ROS levels induced by silica-NPs using DCFDA, and found that amine modi cation of silica-NPs signi cantly attenuated intracellular ROS levels in RAW264.7 cells, which is concordant with previous observations [26] [35].…”

Porous Nanomaterials Targeting Autophagy in Bone Regeneration

“…For example, Wang et al [126] reported that SiNPs increased LC3B expression in hepatocytes in a dose-and time-dependent manner, in accordance with the SiNP-induced cytotoxicity in hepatocytes. The study of Li, M., showed that the cytotoxicity of silica nanoparticles on macrophages was related to surface charge, and the cell survival rate increased with the surface modification of -COOH (negative charge), -NH 2 (positive charge), and polyethylene glycol (PEG, neutral) [127]. However, some researchers have discovered that MSNs have a positive effect on the cell viabilities of macrophages through inducing autophagy.…”

Water-Dispersible, Colloidally Stable, Surface-Functionalizable Uniform Fiberlike Micelles Containing a π-Conjugated Oligo(p-phenylenevinylene) Core of Controlled Length

“…To overcome this problem, cationic trimethylammonium (−NMe 3 + ) groups were incorporated into the cross-linked shell of micelles to promote colloidal stability in water, and amine moieties (−NH 2 ) were introduced for subsequent functionalization. 79,85 Uniform fiberlike micelles (L n = 412 nm, L w /L n = 1.19, Figures 5A and S10A) were first prepared via self-seeding in ethanol, followed by shell-cross-linking by the methods described above (Figure S3, see SI for details) to give uniform micelles with L n of 411 nm (L w /L n = 1.16). Then, (3aminopropyl)triethoxysilane (APTES, 25.4 μL, 0.11 mmol), along with trimethyl [3-(triethoxysilyl)propyl]ammonium chloride (TMTESA, 24.0 mg, 0.08 mmol), were added into micelle dispersion (0.05 mg/mL in ethanol, 12 mL).…”

“…We then attempted to induce in situ cross-linking of the PTESPMA layer of the micelles by siloxane condensation of TES moieties under mild acidic conditions. − Uniform fiberlike micelles with a L n of 358 nm ( L w / L n = 1.18, Figure S6A) were used as a model for these shell-cross-linking reactions. An aqueous HCl solution (160 μL, 1.0 M) was added into the micelle dispersion (0.05 mg/mL in ethanol/THF with 0.5 vol % THF, 16 mL), followed by aging at 23 °C for 24 h. A relatively low micellar concentration (0.05 mg/mL) was used to prevent possible intermicellar cross-linking.…”

“…A number of previous reports have shown that micelles with a crystalline core can undergo fragmentation or disassembly upon transferring from organic solvents to aqueous media. − There are also several examples of PFS block copolymers that preserve their structure under these conditions. ,− The shell-cross-linked OPV 5 - b -PTESPMA micelles described above survived without fragmentation after transfer to water; however, they began to aggregate after several hours (Figure S9B). To overcome this problem, cationic trimethylammonium (−NMe 3 + ) groups were incorporated into the cross-linked shell of micelles to promote colloidal stability in water, and amine moieties (−NH 2 ) were introduced for subsequent functionalization. , …”