The research at Dartmouth Center of Cancer Nanotechnology Excellence consists of 4 projects and is supported by 3 scientific cores.
Schematic of an iron-core nanoparticle with an iron oxide layer and a dextran coating.
The NP Core provides well-characterized magnetic nanoparticles for all project-based research activities. It will develop, produce, and characterize the unique iron/iron oxide core/shell nanocomposite particles that originate at Dartmouth, and it will also characterize and ensure the quality control of nanoparticles purchased either through commercial suppliers or provided by our industrial partners. This oversight of the DCCNE particle use is important during the early stages of the DCCNE's existence while the unique Dartmouth particles are under development. Project 1 will be the earliest recipient and NP Core personnel will work closely with Project 1 leaders to provide these particles.
Specific services provided by the NP Core:
Temperature vs. time for Dartmouth's Fe/Fe3O4 core-shell particles in methanol and commercial dextran-coated Fe oxide in water (5mg/ml).
H = 150 Oe @ 250 kHz
- Produce a range (8-100 nm) of magnetic iron/iron oxide core/shell nanocomposite particles
- Produce biocompatible coatings on the magnetic nanoparticles
- Characterize the magnetic nanoparticle size and size distribution
- Measure the magnetic properties of the magnetic nanoparticles
- Measure the electromagnetic power absorption properties of the magnetic nanoparticles
- Assist project personnel with selection, characterization, and quality control issues associated with the use of commercial and/or corporate-partner purchased and/or supplied nanoparticles for research studies conducted under the auspices of the DCCNE
TEM images of the iron nanoparticle synthesized from microemulsion: (a) O/W = 7:1; (b) O/W = 2.5:1, (c) showing core-shell structure; (d) SAD pattern (110), (200), (220) from α-Fe and (220), (311), (511) from Fe3O4
The TPB Core provides toxicological, pathological, and pharmacokinetic/biodistribution support to the DCCNE projects. The TPB Core builds upon existing expertise within the Norris Cotton Cancer Center's Clinical Pharmacology and Pathology Shared Resources, but it extends considerably services that are specific to the DCCNE.
The primary goal of the TPB Core is to support project investigators in identifying and understanding how magnetic nanoparticle constructs (imaging and therapy, targeted and non-targeted) are distributed in the central vascular compartment (plasma) tumor and normal tissues (organs) over specific post-injection time points. In addition, the TPB Core will provide full pathology and toxicology (gross and histopathological) assessments of tumor and normal tissue changes that may occur as a result of magnetic nanoparticles being administered systemically or intra-tumorally.
Specific services offered by the TPB Core include:
- Bioanalytical and pharmacokinetic analyses
- Pharmacokinetic-pharmacodynamic (PK-PD) modeling
- Toxicokinetic and pathologic evaluation/assays
The TPB Core is vital for determining any toxicity associated with the therapies, which is essential prior to designing clinical trials.
The BDAC Core provides state-of-the-art quantitative data analysis, physical modeling and numerical methods support to the DCCNE projects. Data analyses will focus on the characterization of magnetic nanoparticle properties, quantifying their distribution in tissue and assessing their treatment effect in animal experiments. Statistical considerations will require sophisticated and advanced techniques, including methods for spatial statistics and treatment of multidimensional sources of variation (e.g., variation in time from sample to sample and treatment response from individual to individual). BDAC Core personnel will work closely with project leaders to formulate criteria for validating models through statistical hypothesis testing and optimal design of experiments to achieve statistical significance.
The core will also employ physical modeling and numerical methods in an effort to understand the electromagnetic interactions that occur when magnetic nanoparticles (having different physical properties) are placed in an alternating magnetic field in biological environments and, hence, investigate the impact that biological parameters (e.g., blood flow) are expected to have on the ability to increase tumor temperatures locally.