Michael L. Etheridge

The big picture on nanomedicine: the state of investigational and approved nanomedicine products

UNLABELLED Developments in nanomedicine are expected to provide solutions to many of modern medicines unsolved problems, so it is no surprise that the literature contains many articles discussing the subject. However, existing reviews tend to focus on specific sectors of nanomedicine or to take a very forward-looking stance and fail to provide a complete perspective on the current landscape. This article provides a more comprehensive and contemporary inventory of nanomedicine products. A keyword search of literature, clinical trial registries, and the Web yielded 247 nanomedicine products that are approved or in various stages of clinical study. Specific information on each was gathered, so the overall field could be described based on various dimensions, including FDA classification, approval status, nanoscale size, treated condition, nanostructure, and others. In addition to documenting the many nanomedicine products already in use in humans, this study identifies several interesting trends forecasting the future of nanomedicine. FROM THE CLINICAL EDITOR In this one of a kind review, the state of nanomedicine commercialization is discussed, concentrating only on nanomedicine-based developments and products that are either in clinical trials or have already been approved for use.

Accounting for biological aggregation in heating and imaging of magnetic nanoparticles.

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.

Predictable Heating and Positive MRI Contrast from a Mesoporous Silica-Coated Iron Oxide Nanoparticle

Iron oxide nanoparticles have great potential as diagnostic and therapeutic agents in cancer and other diseases; however, biological aggregation severely limits their function in vivo. Aggregates can cause poor biodistribution, reduced heating capability, and can confound their visualization and quantification by magnetic resonance imaging (MRI). Herein, we demonstrate that the incorporation of a functionalized mesoporous silica shell can prevent aggregation and enable the practical use of high-heating, high-contrast iron oxide nanoparticles in vitro and in vivo. Unmodified and mesoporous silica-coated iron oxide nanoparticles were characterized in biologically relevant environments including phosphate buffered saline, simulated body fluid, whole mouse blood, lymph node carcinoma of prostate (LNCaP) cells, and after direct injection into LNCaP prostate cancer tumors in nude mice. Once coated, iron oxide nanoparticles maintained colloidal stability along with high heating and relaxivity behaviors (SARFe = 204 W/g Fe at 190 kHz and 20 kA/m and r1 = 6.9 mM(-1) s(-1) at 1.4 T). Colloidal stability and minimal nonspecific cell uptake allowed for effective heating in salt and agarose suspensions and strong signal enhancement in MR imaging in vivo. These results show that (1) aggregation can lower the heating and imaging performance of magnetic nanoparticles and (2) a coating of functionalized mesoporous silica can mitigate this issue, potentially improving clinical planning and practical use.

Quantifying iron‐oxide nanoparticles at high concentration based on longitudinal relaxation using a three‐dimensional SWIFT look‐locker sequence

Iron‐oxide nanoparticles (IONPs) have proven utility as contrast agents in many MRI applications. Previous quantitative IONP mapping has been performed using mainly T2* mapping methods. However, in applications requiring high IONP concentrations, such as magnetic nanoparticles based thermal therapies, conventional pulse sequences are unable to map T2* because the signal decays too rapidly. In this article, sweep imaging with Fourier transformation (SWIFT) sequence is combined with the Look‐Locker method to map T1 of IONPs in high concentrations.

RF heating of magnetic nanoparticles improves the thawing of cryopreserved biomaterials

While vitrified cryopreservation holds great promise, practical application has been limited to smaller systems (cells and thin tissues) due to diffusive heat and mass transfer limitations, which are typically manifested as devitrification and cracking failures during thaw. Here then we describe a new approach for rapidly and uniformly heating cryopreserved biospecimens with radiofrequency (RF) excited magnetic nanoparticles (mNPs). Importantly, heating rates can be increased several fold over conventional boundary heating techniques and are independent of sample size. Initial differential scanning calorimetry studies indicate that the addition of the mNPs has minimal impact on the freeze-thaw behavior of the cryoprotectant systems themselves. Then proof-of-principle experiments in aqueous and cryoprotectant solutions demonstrate the ability to heat at rates high enough to mitigate or eliminate devitrification (hundreds of °C/min) and scaled heat transfer modeling is used to illustrate the potential of this innovative approach. Finally, X-ray micro-computed-tomography (micro-CT) is investigated as a planning and quality control tool, where the density-based measurements are able to quantify changes in cryoprotectant concentration, mNP concentration, and the frozen state (i.e. crystallized versus vitrified).

THE BIG PICTURE ON SMALL MEDICINE: THE STATE OF NANOMEDICINE PRODUCTS APPROVED FOR USE OR IN CLINICAL TRIALS

UNLABELLED Developments in nanomedicine are expected to provide solutions to many of modern medicines unsolved problems, so it is no surprise that the literature contains many articles discussing the subject. However, existing reviews tend to focus on specific sectors of nanomedicine or to take a very forward-looking stance and fail to provide a complete perspective on the current landscape. This article provides a more comprehensive and contemporary inventory of nanomedicine products. A keyword search of literature, clinical trial registries, and the Web yielded 247 nanomedicine products that are approved or in various stages of clinical study. Specific information on each was gathered, so the overall field could be described based on various dimensions, including FDA classification, approval status, nanoscale size, treated condition, nanostructure, and others. In addition to documenting the many nanomedicine products already in use in humans, this study identifies several interesting trends forecasting the future of nanomedicine. FROM THE CLINICAL EDITOR In this one of a kind review, the state of nanomedicine commercialization is discussed, concentrating only on nanomedicine-based developments and products that are either in clinical trials or have already been approved for use.

Quantifying iron-oxide nanoparticles at high concentration based on longitudinal relaxation using a 3D SWIFT Look-Locker sequence

Iron‐oxide nanoparticles (IONPs) have proven utility as contrast agents in many MRI applications. Previous quantitative IONP mapping has been performed using mainly T2* mapping methods. However, in applications requiring high IONP concentrations, such as magnetic nanoparticles based thermal therapies, conventional pulse sequences are unable to map T2* because the signal decays too rapidly. In this article, sweep imaging with Fourier transformation (SWIFT) sequence is combined with the Look‐Locker method to map T1 of IONPs in high concentrations.

The big picture on nanomedicine

UNLABELLED Developments in nanomedicine are expected to provide solutions to many of modern medicines unsolved problems, so it is no surprise that the literature contains many articles discussing the subject. However, existing reviews tend to focus on specific sectors of nanomedicine or to take a very forward-looking stance and fail to provide a complete perspective on the current landscape. This article provides a more comprehensive and contemporary inventory of nanomedicine products. A keyword search of literature, clinical trial registries, and the Web yielded 247 nanomedicine products that are approved or in various stages of clinical study. Specific information on each was gathered, so the overall field could be described based on various dimensions, including FDA classification, approval status, nanoscale size, treated condition, nanostructure, and others. In addition to documenting the many nanomedicine products already in use in humans, this study identifies several interesting trends forecasting the future of nanomedicine. FROM THE CLINICAL EDITOR In this one of a kind review, the state of nanomedicine commercialization is discussed, concentrating only on nanomedicine-based developments and products that are either in clinical trials or have already been approved for use.

Investigating Electromagnetic Field, Nanoparticle Design, and Treatment Volume for Magnetic Nanoparticle Thermal Therapy

Magnetic nanoparticle (MNP) based thermal therapies are currently approved in Europe and poised for clinical translation in the US. The main benefits include the ability to focally and repeatedly treat tissues, including cancers, with a minimally-invasive platform. Nevertheless, a more complete understanding and control of MNP heating is necessary to effectively translate the approach to treat different sizes and geometries of cancer (See Figure 1). The present work discusses contrasts in heating between superparamagnetic and ferromagnetic nanoparticles (sMNP and fMNP), electromagnetic field-dependant MNP response, scaling of MNP volumetric heating, and the ability of theory to predict this behavior.Copyright

Quantifying iron-oxide nanoparticles at high concentration based on longitudinal relaxation using a three-dimensional SWIFT look-locker sequence: 3D SWIFT Look-Locker T1Mapping on IONPs

Iron‐oxide nanoparticles (IONPs) have proven utility as contrast agents in many MRI applications. Previous quantitative IONP mapping has been performed using mainly T2* mapping methods. However, in applications requiring high IONP concentrations, such as magnetic nanoparticles based thermal therapies, conventional pulse sequences are unable to map T2* because the signal decays too rapidly. In this article, sweep imaging with Fourier transformation (SWIFT) sequence is combined with the Look‐Locker method to map T1 of IONPs in high concentrations.