Biocompatibility of Multi-Imaging Engineered Mesoporous Silica Nanoparticles: In Vitro and Adult and Fetal In Vivo Studies

Abstract

Despite potentially serious adverse effects of engineered nanoparticles on maternal health and fetal development, little is known about their transport across the placenta. Human and animal studies are primarily limited to ex vivo approaches; the lack of a real-time, minimally invasive tool to study transplacental transport is clear. We have developed functionalized mesoporous silica nanoparticles (MSN) for use in magnetic resonance, ultrasound, and fluorescent imaging. This material is designed as a model for, or a carrier of, environmental toxicants, allowing for in vivo evaluation. To establish a baseline of biocompatibility, we present data describing MSN tolerance using in vitro and in vivo models. In cultured cells, MSN were tolerated to a dose of 125 µg/mL with minimal effect on viability and doubling time. For the 42 day duration of the study, none of the mice exhibited behaviors usually indicative of distress (lethargy, anemia, loss of appetite, etc.). In gravid mice, the body and organ weights of MSN-exposed dams were equivalent to those of control dams. Embryos exposed to MSN during early gestation were underweight by a small degree, while embryos exposed during late gestation were of a slightly larger weight. The rate of spontaneous fetal resorptions were equivalent in exposed and control mice. Maternal livers and sera were screened for a complement of cytokines/chemokines and reactive oxygen/nitrogen species (ROS/RNS). Only granulocyte-colony stimulating factor was elevated in mice exposed to MSN during late gestation, while ROS/RNS levels were elevated in mice exposed during early/mid gestation. These findings may usher future experiments investigating environmental toxicants using real-time assessment of transport across the placenta.

Multifunctional nanoparticles for real-time evaluation of toxicity during fetal development

“…To ensure a homogeneous particle size and morphology, the particles were characterized after each step in the synthesis and were reported previously [ 30 – 32 ]. Briefly, the Gd 2 O 3 colloid prepared in diethylene glycol was measured by DLS, having a number PSD-based radius of 7.4 nm and a polydispersity index of 0.209.…”

“…When compared with MSN not bearing trifluoropropyl groups, the TFP-FITC-Gd 2 O 3 -MSN agars also generated a clear ultrasound contrast. Additionally, we observed contrast changes in vivo when previously evaluating the biocompatibility of the particles [ 30 ]. Powder XRD analysis confirmed ordered pores in the diffraction pattern of the Gd 2 O 3 -MSN as evident by an intense d 100 peak at 2.5 2θ, and well resolved d 110 and d 200 peaks at 3.83 and 4.40 2θ, respectively.…”

“…First, a gadolinium oxide-MSN core was manufactured as reported previously [ 30 – 32 ], yielding 1.79 grams. Next, FITC (5.0 mg, 0.0128 mmol) was reacted with aminopropyltrimethoxysilane (2.2345 μL, 0.0128 mmol) in DMSO (1 mL) for 2 hours, and FITC-Gd 2 O 3 -MSN was prepared by grafting 0.05 mL of the resulting product on the previously synthesized Gd 2 O 3 -MSN (100 mg) in toluene (25 mL) under reflux for 24 hours.…”

“…We predict applicability in clinically relevant imaging modalities (MRI, ultrasound) as well as in study in nano-size toxicant in animal models. Given that our particle compounds are not toxic based on systematic studies [ 30 ], we envision the covalent linking of difficult to track environmental pollutants of interest, and use of this technology as vehicles for real-time, non-invasive studies.…”

Physical‐, chemical‐, and biological‐responsive nanomedicine for cancer therapy

“…(Longmire, Choyke, & Kobayashi, 2008). Fortunately, many excellent researchers have studied the metabolism of the nanoparticles and have made great progress (D. Liu, Poon, Lu, He, & Lin, 2014;Niemirowicz et al, 2017;Sweeney, Adamcakovadodd, Thorne, & Assouline, 2017). Gold nanoparticles and iron oxide nanoparticles with small particle size (within 6 nm) can be cleared by the kidneys (H. Deng, Dai, Ma, & Zhang, 2015).…”