Page 68 - ASME_NEMB_2016_Program

Technical Program TRACK 5

microstructures replacing those ridges completely. These hierarchical struc- Magnetic iron oxide nanoparticles (MNPs) possess the unique ability to be
tures significantly enlarge the specific surface area of silica, enhancing DNA used in both a diagnostic and therapeutic capacity for cancer treatment by
absorption capability on the nanomembrane. We compared the performanc- utilizing their inherent magnetic resonance contrast and potential to gener-
es of our nanomembrane with commercial particles for DNA re-isolation in ate local heat when exposed to an alternating magnetic field (AMF). Recent
three aspects: recovery yield, purity and integrity. We were able to recover advances in the synthesis of MNPs through thermal decomposition have
about 3.2 microgram (80%) using our nanomembrane from 4 microgram ge- enabled fine size tuning within a wide range for distinct and monodisperse
nomic DNA, while magnetic particles only recovered about 20% DNA under populations. This level of control prompts an in-depth investigation of the
the same condition. DNA shearing induced by commercial particles was also nano size effects in magnetic fluid hyperthermia (MFH) and magnetic reso-
observed by running resulting DNA in gel electrophoresis. DNA isolated us- nance imaging (MRI). Here we synthesized an extensive array of MNPs and
ing small particles (100nm in diameter) were sheared much more significant- examined the influence of nanoparticle size for MRI and MFH at the solution,
ly compared with using large particles (5um in diameter). In contrast, DNA cellular, and tissue levels.
isolated using the silica nanomembrane retained their integrity. We also per-
formed DNA extraction from cultured cells utilizing our nanomembrane, and In this study, 8 different magnetite nanocrystals from 6 to 40 nm were
gel electrophoresis result demonstrated that the yield DNA had significantly synthesized by thermodecomposition of iron acetylacetonate. The room
high molecular weight DNA, over 50kb, comparable with those extracted temperature M-H curves for all nanocrystals exhibit minimal hysteresis and
through phenol/chloroform method in both yield and quality. Moreover, with high saturation magnetization approaching that of bulk magnetite. The nano-
the same amount of cultured cells as input (about 3 million), DNA yield using crystals below 10 nm in diameter have a reduced saturation magnetization
column and magnetic particles are only about 42% and 56% of that using in contrast to larger nanocrystals, suggesting the influence of a disordered
our nanomenbrane. surface layer on magnetization increases with the surface to volume ratio.
To confer aqueous solubility, the nanocrystals were coated with phospho-
Conclusions: In summary, we have demonstrated a novel method to fab- lipid-PEG using a dual solvent exchange method. Dynamic light scattering
ricate silica nanostructures based on self-wrinkling induced by thermal measurements showed that the coated MNPs were monodisperse in water.
shrinkage. The formation of overlaying hierarchical nanostructures on the The minimal hysteresis loop in the M-H curves of these MNPs suggests that
membrane is closely related to the thicknesses of silica deposition. These the primary mechanism of AMF heat generation can be attributed to Néelian
hierarchical nanostructures have vastly enlarged the specific area of silica, and Brownian relaxation. We found that when aqueous solutions of MNPs
thus enabling us to implement the nanomembrane in solid phase DNA were exposed to AMF, there was very low heating below 10 nm and a linear
extraction. We applied the silica nanomembrane for DNA extraction and relationship between the specific absorption rate (SAR) and the nanoparticle
demonstrated its better performance than commercial columns and parti- size above 10 nm. The maximum SAR was achieved with the 40 nm nano-
cles, in terms of DNA yield and quality. Therefore, we expect this hierarchical crystals at 2844 W/g with an AMF setting of 23.8 kA/m and 325 kHz. When
nanomembrane to be widely adapted in various DNA analyses. the MNPs were dispersed in glycerol, there was no significant change in
SAR, indicating that Néelian relaxation is dominating in heat generation. In
addition, our numerical analysis showed that the size dependence of SAR
could be explained by accounting for the contribution of the surface layer
WEDNESDAY, FEBRUARY, 24 to the anisotropic energy of MNPs. In the meantime, the MRI T2 contrast of
MNPs was assessed with a 0.47T Minispec Analyzer. Interestingly, there is
also a linear increase in the relaxivity with respect to the size of MNPs, with
5-6 the highest relaxivity occurring in the 40 nm MNPs at 850 mM-1s-1.
NANOPARTICLE SYNTHESIS The tumor tissue represents a heterogeneous microenvironment for MRI
and complicated thermodynamics for MFH due to homeostatic temperature
regulation. To this end, MNPs of 6 nm, 19 nm or 40 nm were examined in a
Hidalgo 9:30am - 11:00am mouse xenograft tumor model. After intratumoral injection of 50 µg of MNPs,
MR images clearly delineated the injection volume of MNPs of all sizes.
However, AMF treatment of the tumors injected with the 6 nm MNPs did not
9:30am Engineering magnetic nanoparticles for biomedical ap- induce an increase in temperature, while the 19 nm and 40 nm MNPs caused
plications in time-varying magnetic fields (Invited) an increase of 2.5 and 10.1 degree respectively. In histological examination,
only the 40 nm MNP-treated tumors showed strong TUNEL staining, which is
Keynote. NEMB2016-6038 consistent with the temperature measurements.

Carlos Rinaldi, University of Florida, Gainesville, FL, United States In summary, our study shows a linear correlation of SAR and T2 relaxivity
with respect to the size of magnetite nanocrystals as a result of the size-de-
Magnetic nanoparticles are unique among nanomaterials due to our ability pendency of their magnetic properties. Developing MNPs for MRI and MFH
to control their translation and rotation, and actuate thermal release, through applications requires careful consideration of the physicochemical proper-
the application of magnetic field gradients and time-varying magnetic fields. ties of the particles in order to achieve peak efficiency.
Furthermore, because of their biocompability and the fact that magnetic
fields penetrate through the body, magnetic nanoparticles possess tre- 10:20am Large-Scale Nanoparticle Synthesis through High Pre-
mendous potential for biomedical applications. In this talk I will discuss our cision Feedback Control of Parallelized Microfluidic Reactors
recent work aimed at engineering magnetic nanoparticles to tailor their
response to time-varying magnetic fields and for their application in thermal Technical Presentation. NEMB2016-6112
cancer therapy, magnetic particle imaging, and probing the mechanical
properties of biological environments.
Michael Toth, YongTae Kim, Georgia Institute of Technology, Atlan-
ta, GA, United States
10:00am Size Dependency for Magnetic Resonance Contrast
and Magnetic Fluid Hyperthermia
A wide range of nanoparticles (NPs) has been developed with the potential
to revolutionize therapeutics and diagnostics through targeted delivery of
Technical Presentation. NEMB2016-6023 drugs/genes and selective combination of imaging agents to specific cells/
tissues. Recent approaches using microfluidics produced NPs with higher
Christopher Quinto, Georgia Institute of Technology, Atlanta, GA, reproducibility by facilitating the micro- and nanoscale interactions of precur-
68 United States, Sheng Tong, Gang Bao, Rice University, Houston, sors in synthesizing several types of NPs than that of conventional bulk syn-
TX, United States thesis. However, these microfluidics-based NP syntheses have been largely
limited to small-scale production of specific single component NPs. There