BackgroundAs the prevalence of therapeutic approaches involving transplanted cells increases, so does the need to noninvasively track the cells to determine their homing patterns. Of particular interest is the fate of transplanted embryonic stem cell-derived hematopoietic progenitor cells (HPCs) used to restore the bone marrow pool following sublethal myeloablative irradiation. The early homing patterns of cell engraftment are not well understood at this time. Until now, longitudinal studies were hindered by the necessity to sacrifice several mice at various time points of study, with samples of the population of lymphoid compartments subsequently analyzed by flow cytometry or fluorescence microscopy. Thus, long-term study and serial analysis of the transplanted cells within the same animal was cumbersome, making difficult an accurate documentation of engraftment, functionality, and cell reconstitution patterns.MethodsHere, we devised a noninvasive, nontoxic modality for tracking early HPC homing patterns in the same mice longitudinally over a period of 9 days using mesoporous silica nanoparticles (MSNs) and magnetic resonance imaging.ResultsThis approach of potential translational importance helps to demonstrate efficient uptake of MSNs by the HPCs as well as retention of MSN labeling in vivo as the cells were traced through various organs, such as the spleen, bone marrow, and kidney. Altogether, early detection of the whereabouts and engraftment of transplanted stem cells may be important to the overall outcome. To accomplish this, there is a need for the development of new noninvasive tools.ConclusionsOur data suggest that multifunctional MSNs can label viably blood-borne HPCs and may help document the distribution and homing in the host followed by successful reconstitution.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0944-8) contains supplementary material, which is available to authorized users.

BackgroundDespite being one of the most common cancers, bladder cancer is largely inefficiently and inaccurately staged and monitored. Current imaging methods detect cancer only when it has reached “visible” size and has significantly disrupted the structure of the organ. By that time, thousands of cells will have proliferated and perhaps metastasized. Repeated biopsies and scans are necessary to determine the effect of therapy on cancer growth. In this report, we describe a novel approach based on multimodal nanoparticle contrast agent technology and its application to a preclinical animal model of bladder cancer. The innovation relies on the engineering core of mesoporous silica with specific scanning contrast properties and surface modification that include fluorescence and magnetic resonance imaging (MRI) contrast. The overall dimensions of the nano-device are preset at 80–180 nm, depending on composition with a pore size of 2 nm. MethodsTo facilitate and expedite discoveries, we combined a well-known model of bladder cancer and our novel technology. We exposed nanoparticles to MB49 murine bladder cancer cells in vitro and found that 70 % of the cells were labeled by nanoparticles as measured by flow cytometry. The in vivo mouse model for bladder cancer is particularly well suited for T1- and T2-weighted MRI. ResultsUnder our experimental conditions, we demonstrate that the nanoparticles considerably improve tumor definition in terms of volumetric, intensity and structural characteristics. Important bladder tumor parameters can be ascertained, non-invasively, repetitively, and with great accuracy. Furthermore, since the particles are not biodegradable, repetitive injection is not required. This feature allows follow-up diagnostic evaluations during cancer treatment. Changes in MRI signals show that in situ uptake of free particles has predilection to tumor cells relative to normal bladder epithelium. The particle distribution within the tumors was corroborated by fluorescent microscopy of sections of excised bladders. In addition, MRI imaging revealed fibrous finger-like projections into the tumors where particles insinuated themselves deeply. This morphological characteristic was confirmed by fluorescence microscopy. ConclusionsThese findings may present new options for therapeutic intervention. Ultimately, the combination of real-time and repeated MRI evaluation of the tumors enhanced by nanoparticle contrast may have the potential for translation into human clinical studies for tumor staging, therapeutic monitoring, and drug delivery.

No 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.