Magnatic Nanoparticles and Nanocomposites: Development for Medical and Environmental Applications

We apply chemical engineering fundamentals to the rational design, synthesis, and application of novel nanoparticle systems and macromolecular materials. In particular, we are interested in designing and applying advanced materials based on magnetic nanoparticles (MNPs) and nanocomposites. Magnetic nanocomposites are a relatively new class of advanced materials, which have attracted interest as intelligent materials for biomaterial and other applications. In our lab, we are primarily interested in MNPs due to their ability to respond to an alternating magnetic field (AMF) resulting in local energy delivery and potentially localized heating. We have incorporated MNPs into nanocomposites that exhibit new and unique properties such as remote actuation, and the resultant properties of the nanocomposite can be easily tailored by manipulating the composition of the polymer and the nanoparticulate material. Here, some of our recent activities in the development and application of MNPs and their nanocomposites will be presented. In particular, the application of functionalized MNPs for cancer therapy and environmental remediation will be highlighted. For potential cancer therapy applications, we have been particularly interested in determining the role of reactive oxygen species (ROS) catalytically generated from the surface of iron oxide MNPs, and using a methylene blue degradation assay, we demonstrated that magnetically mediated energy delivery (MagMED) is capable of enhancing the Fenton-like generation of ROS. Here, further studies of the surface reactivity of MNPs and the enhancement of this reactivity with AMF exposure will be presented, as well as the effects of small molecule and macromolecular coatings. These demonstrations illustrate the potential of AMF-induced ROS in cancer therapy. For environmental applications, AMF exposure and the associated energy delivery can be used to carry out various functions. For example, we will present data showing the AMF exposure being used to change the binding properties of an MNP coating

Addressing PFAS Contamination in Blood Bank Supplies with Hydrogel Nanocomposite Sorbents

Environmental pollutants continue to be a threat to global human health. Persistent contaminants, such as perfluoroalkyl substances (PFAS), have been linked to a multitude of adverse health effects such as cancerous tumors, increased blood cholesterol levels and liver damage. The dominant source of exposure to PFAS is through contaminated drinking water, and accumulation has been found to occur significantly in human blood serum. Thus, high-risk groups who are receiving frequent blood transfusions are exposed to these harmful chemicals in a dual fashion, which could prove detrimental. Traditional sorbents that display an affinity for PFAS include powdered activated carbon and clay. Recently, a protein found in plasma, albumin, has been identified as the major carrier protein for PFAS in human blood. The two most widely detected PFAS in human serum are perfluorooctanesulfonic acid, PFOS, and perfluorooctanoic acid, PFOA. As such, this work aims to develop hydrogel nanocomposites that have the capability to remove PFOA and PFOS from human blood serum. Crosslinked acrylamide polymers were synthesized with varied crosslinking densities of 0.1 mol%, 1 mol%, and 10 mol% to evaluate potential exclusion of serum proteins. In order to incorporate physiochemical properties of sorbents known to bind PFOA and PFOS, varied amounts of dried particulates were integrated into the synthesized hydrogels. Powdered activated carbon, sodium montmorillonite clay, and bovine serum albumin were studied at loadings of 1 wt% and 5 wt% respective to total reactant weight. The synthesized hydrogels were characterized via FTIR and TGA analysis. Competitive binding to evaluate PFOA and PFOS affinity was completed in a binding matrix of pH 7.4, similar to that of blood serum

Recent Advances on Iron Oxide Magnetic Nanoparticles as Sorbents of Organic Pollutants in Water and Wastewater Treatment

The constant growth in population worldwide over the past decades continues to put forward the need to provide access to safe, clean water to meet human needs. There is a need for cost-effective technologies for water and wastewater treatment that can meet the global demands and the rigorous water quality standards and at the same maximizing pollutant efficiency removal. Current remediation technologies have failed in keeping up with these factors without becoming cost-prohibitive. Most recently, nanotechnology has been sought as the best alternative to increase access to water supplies by remediating those already contaminated and offering ways to access unconventional sources. The use of iron oxide magnetic nanoparticles as nanoadsorbents has led way to a new class of magnetic separation strategies for water treatment. This review focuses on highlighting some of the most recent advances in core-shell iron oxide magnetic nanoparticles and nanocomposites containing iron oxide nanoparticles currently being developed for water and wastewater treatment of organic pollutants. We discuss the novelty of these novel materials and the insight gained from their advances that can help develop cost-effective reusable technologies for scale-up and commercial use

Treating Proximal Tibial Growth Plate Injuries Using Poly(Lactic-co-Glycolic Acid) Scaffolds

Growth plate fractures account for nearly 18.5% of fractures in children. Depending on the type and severity of the injury, inhibited bone growth or angular deformity caused by bone forming in place of the growth plate can occur. The current treatment involves removal of the bony bar and replacing it with a filler substance, such as a free fat graft. Unfortunately, reformation of the bony bar frequently occurs, preventing the native growth plate from regenerating. The goal of this pilot study was to determine whether biodegradable scaffolds can enhance native growth plate regeneration following a simulated injury that resulted in bony bar formation in the proximal tibial growth plate of New Zealand white rabbits. After removing the bony bar, animals received one of the following treatments: porous poly(lactic-co-glycolic acid) (PLGA) scaffold; PLGA scaffold loaded with insulin-like growth factor I (IGF-I); PLGA scaffold loaded with IGF-I and seeded with autogenous bone marrow cells (BMCs) harvested at the time of implantation; or fat graft (as used clinically). The PLGA scaffold group showed an increased chondrocyte population and a reduced loss of the remaining native growth plate compared to the fat graft group (the control group). An additional increase in chondrocyte density was seen in scaffolds loaded with IGF-I, and even more so when BMCs were seeded on the scaffold. While there was no significant reduction in the angular deformation of the limbs, the PLGA scaffolds increased the amount of cartilage and reduced the amount of bony bar reformation

Compounds and Methods for Reducing Oxidative Stress

Antioxidant polymeric compounds are provided that comprise a plurality of monomeric portions, where each monomeric portion includes an antioxidant molecule interposed between at least two acrylate molecules, and where at least one acrylate molecule of each monomeric portion is linked by a diamine molecule to an acrylate molecule of an adjacent monomeric portion to thereby form the polymer. Methods of synthesizing polymeric compounds and methods of using the antioxidant polymeric compounds to reduce oxidative stress are also provided

Development of Novel \u3cem\u3eN\u3c/em\u3e-isopropylacrylamide (NIPAAm) Based Hydrogels with Varying Content of Chrysin Multiacrylate

A series of novel temperature responsive hydrogels were synthesized by free radical polymerization with varying content of chrysin multiacrylate (ChryMA). The goal was to study the impact of this novel polyphenolic-based multiacrylate on the properties of N-isopropylacrylamide (NIPAAm) hydrogels. The temperature responsive behavior of the copolymerized gels was characterized by swelling studies, and their lower critical solution temperature (LCST) was characterized through differential scanning calorimetry (DSC). It was shown that the incorporation of ChryMA decreased the swelling ratios of the hydrogels and shifted their LCSTs to a lower temperature. Gels with different ChryMA content showed different levels of response to temperature change. Higher content gels had a broader phase transition and smaller temperature response, which could be attributed to the increased hydrophobicity being introduced by the ChryMA

Highly Thiolated Poly (Beta-Amino Ester) Nanoparticles for Acute Redox Applications

Disulfides are used extensively in reversible cross-linking because of the ease of reduction into click-reactive thiols. However, the free-radical scavenging properties upon reduction are often under-considered. The free thiols produced upon reduction of this disulfide material mimic the cellular reducing chemistry (glutathione) that serves as a buffer against acute oxidative stress. A nanoparticle formulation producing biologically relevant concentrations of thiols may not only provide ample chemical conjugation sites, but potentially be useful against severe acute oxidative stress exposure, such as in targeted radioprotection. In this work, we describe the synthesis and characterization of highly thiolated poly (β-amino ester) (PBAE) nanoparticles formed from the reduction of bulk disulfide cross-linked PBAE hydrogels. Degradation-tunable PBAE hydrogels were initially synthesized containing up to 26 wt % cystamine, which were reduced into soluble thiolated oligomers and formulated into nanoparticles upon single emulsion. These thiolated nanoparticles were size-stable in phosphate buffered saline consisting of up to 11.0 ± 1.1 mM (3.7 ± 0.3 mmol thiol/g, n = 3 M ± SD), which is an antioxidant concentration within the order of magnitude of cellular glutathione (1–10 mM)

Synthesis and Characterization of CREKA-Conjugated Iron Oxide Nanoparticles for Hyperthermia Applications

One of the current challenges in the systemic delivery of nanoparticles in cancer therapy applications is the lack of effective tumor localization. Iron oxide nanoparticles coated with crosslinked dextran were functionalized with the tumor homing peptide CREKA, which binds to fibrinogen complexes in the extracellular matrix of tumors. This allows for the homing of these nanoparticles to tumor tissue. The iron oxide nanoparticle core allows for particle heating upon exposure to an alternating magnetic field (AMF) while the dextran coating stabilizes the particles in suspension and decreases the cytotoxicity of the system. Magnetically mediated hyperthermia (MMH) allows for the heating of tumor tissue to increase the efficacy of traditional cancer treatments using the iron oxide nanoparticles. While MMH provides the opportunity for localized heating, this method is currently limited by the lack of particle penetration into tumor tissue, even after effective targeted delivery to the tumor site. The CREKA-conjugated nanoparticles presented were characterized for their size, stability, biocompatibility, and heating capabilities. The particles were stable in PBS and media over at least twelve hours, had a hydrated diameter of 52 nm, and generated enough heat to raise solution temperatures well into the hyperthermia range (41 – 45 °C) when exposed to an AMF. Biocompatibility studies demonstrated that the particles have low cytotoxicity over long exposure times at low concentrations. A fibrinogen clotting assay was used to determine the binding affinity of CREKA-conjugated particles, which was significantly greater than the binding affinity of dextran, only coated iron oxide nanoparticles demonstrating the potential for this particle system to effectively home to a variety of tumor locations. Finally, it was shown that in vitro MMH increased the effects of cisplatin compared to cisplatin or MMH treatments alone