Higher cationic charge density on nanoparticles is correlated with higher toxicity to bacteria.

Aggregation is a known consequence of nanoparticle use in biology and medicine; however, nanoparticle characterization is typically performed under the pretext of well-dispersed, aqueous conditions. Here, we systematically characterize the effects of aggregation on the alternating magnetic field induced heating and magnetic resonance (MR) imaging performance of iron oxide nanoparticles (IONPs) in non-ideal biological systems. Specifically, the behavior of IONP aggregates composed of ~10 nm primary particles, but with aggregate hydrodynamic sizes ranging from 50 nm to 700 nm, was characterized in phosphate buffered saline and fetal bovine serum suspensions, as well as in gels and cells. We demonstrate up to a 50% reduction in heating, linked to the extent of aggregation. To quantify aggregate morphology, we used a combination of hydrodynamic radii distribution, intrinsic viscosity, and electron microscopy measurements to describe the aggregates as quasifractal entities with fractal dimensions in the 1.8–2.0 range. Importantly, we are able to correlate the observed decrease in magnetic field induced heating with a corresponding decrease in longitudinal relaxation rate (R1) in MR imaging, irrespective of the extent of aggregation. Finally, we show in vivo proof-of-principle use of this powerful new imaging method, providing a critical tool for predicting heating in clinical cancer hyperthermia.

Practical biomedical application of mesoporous silica nanoparticles is limited by poor particle dispersity and stability due to serious irreversible aggregation in biological media. To solve this problem, hydrothermally treated mesoporous silica nanoparticles of small size with dual-organosilane (hydrophilic and hydrophobic silane) surface modification have been synthesized. These highly organomodified mesoporous silica nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, N(2) adsorption-desorption, dynamic light scattering, zeta potential, and solid-state (29)Si NMR, and they prove to be very stable in simulated body fluid at physiological temperature. Additionally, they can be dried to a powdered solid and easily redispersed in biological media, maintaining their small size for a period of at least 15 days. Furthermore, this preparation method can be expanded to synthesize redispersible fluorescent and magnetic mesoporous silica nanoparticles. The highly stable and redispersible mesoporous silica NPs show minimal toxicity during in vitro cellular assays. Most importantly, two types of doxorubicin, water-soluble doxorubicin and poorly water-soluble doxorubicin, can be loaded into these highly stable mesoporous silica nanoparticles, and these drug-loaded nanoparticles can also be well-redispersed in aqueous solution. Enhanced cytotoxicity to cervical cancer (HeLa) cells was found upon treatment with water-soluble doxorubicin-loaded nanoparticles compared to free water-soluble doxorubicin. These results suggest that highly stable, redispersible, and small mesoporous silica nanoparticles are promising agents for in vivo biomedical applications.

Nickel manganese cobalt oxide (NMC) comprises a class of lithium intercalation compounds with the composition L x Ni y Mn z Co 1-y-z O 2 (0 < x,y,z < 1). These compounds are of emerging importance in nanoparticle form as cathode materials for lithium-ion batteries used in transportation and consumer electronics. To evaluate the potential environmental impact of release of this material in the environment, we synthesized NMC nanosheets and investigated their interaction with Shewanella oneidensis, a soil and sediment bacterium. Exposure to 5 mg/L NMC significantly impaired bacterial population growth and respiration. Measurements of NMC surface composition by X-ray photoelectron spectroscopy and of the composition of the suspending solution via inductively coupled plasma-optical emission spectroscopy (ICP-OES) demonstrated incongruent material dissolution and measurable release of all four metal constituents (Li, Mn, Co, and Ni) into solution. Speciation modeling and assessment of bacterial response to metal ion exposure (via cell growth and respiration measurements) established that the observed bacterial inhibition arose from the metal ions released from the NMC, with the largest effects arising from Ni(II) and Co(II) species.

Since the first report of mesoporous silica nanoparticles in 2001, many efforts have been made to develop them for biomedical applications. With the emergence of new designs and increasingly complex synthetic schemes, mesoporous silica nanoparticles have never been more promising. For this promise to be fulfilled, however, practical considerations for biomedical use must be carefully addressed. Many current mesoporous silica reports, even those reporting in vivo work, neglect the observation of nanoparticle size, pore structure, aggregation state, and biodegradability under biological conditions before administration. These critical considerations, beginning at synthetic stages, must be taken into account to make effective and safe mesoporous silica nanoparticles for biomedical use and timely application in clinical trials. Herein, we present a comprehensive review of mesoporous silica nanoparticle synthetic strategies, pointing out nanoparticle behavior under biological conditions and how it may affect in vitro and in vivo results.