Towner R.A.,Oklahoma Medical Research Foundation |
Smith N.,Oklahoma Medical Research Foundation |
Asano Y.,Oklahoma Medical Research Foundation |
He T.,Oklahoma Medical Research Foundation |
And 5 more authors.
Tissue Engineering - Part A | Year: 2010
In tissue engineering it is often necessary to assess angiogenesis associated with engineered tissue grafts. The levels of vascular endothelial growth factor receptor 2 (VEGF-R2) is elevated during angiogenesis. The goal of this study was to develop and assess a novel magnetic resonance imaging (MRI) molecular probe for the in vivo detection of VEGF-R2 in an experimental rodent model of disease. The possible use of the probe in tissue engineering applications is discussed. The molecular targeting agent we used in our study incorporated a magnetite-based dextran-coated nanoparticle backbone covalently bound to an anti-VEGF-R2 antibody. We used molecular MRI with an anti-VEGF-R2 probe to detect in vivo VEGF-R2 levels as a molecular marker for gliomas (primary brain tumors). Tumor regions were compared with normal tissue. Nonimmune nonspecific normal rat immunoglobulin G coupled to the dextran-coated nanoparticles was used as a control. Prussian blue staining for iron-based nanoprobes was used to confirm the specificity of the probe for VEGF-R2 in glioma tissue. VEGF-R2 levels in tumor tissues were also confirmed in western blots and via immunohistochemistry. Based on our results, in vivo evaluation of tissue angiogenesis using molecular MRI is possible in tissue engineering applications. Copyright 2010, Mary Ann Liebert, Inc.
Seeney C.,NanobioMagnetics Inc. |
Ojwang J.O.,NanobioMagnetics Inc. |
Weiss R.D.,Arkival Technology Corporation |
Klostergaard J.,University of Houston
Nanomedicine | Year: 2012
Superparamagnetic iron oxide nanoparticles (SPIONs) are being developed as vehicles for the selective targeting of therapeutics and bioactive compounds. Presented herein is a brief review of the history of approaches to magnetic-based drug delivery platforms, leading to current concepts of magnetically vectored therapeutics via functionalized SPION-prodrugs. With this background, recent experimental results are discussed that demonstrate the use of shaped external magnetic field gradients, generated by designed configurations of permanent magnets, to drive the concentration/accumulation of modified SPION-prodrug constructs at a tumor site, followed by tumor extravasation and activation of the prodrug within the tumor microenvironment. In order to successfully translate this approach to clinical application, one of the key requirements is the ability to magnetically drive ('vector') the SPION to human-scale tumor settings. In this review, various configurations of permanent magnets are described and models are presented that demonstrate that magnetic field gradients can potentially be focused and extended to lengths of several inches in vivo. This modification thereby increases the range of the delivery platform, and offers the potential for the treatment of visceral as well as superficial tumors and for translation from preclinical animal tumor models to clinical settings. The methodology of magnetically vectored prodrug therapeutics, as a means for selective localized targeting of tumor tissue, and minimizing harm to normal tissue, has the additional advantage of raising the therapeutic index compared with that of free drugs, thus, offering great potential as a cancer treatment modality. © 2012 Future Medicine Ltd.
Klostergaard J.,University of Houston |
Seeney C.E.,NanoBioMagnetics Inc.
Maturitas | Year: 2012
Nanotechnology holds the promise of novel and more effective treatments for vexing human health issues. Among these are the use of nanoparticle platforms for site-specific delivery of therapeutics to tumors, both by passive and active mechanisms; the latter includes magnetic vectoring of magnetically responsive nanoparticles (MNP) that are functionalized to carry a drug payload that is released at the tumor. The conceptual basis, which actually dates back a number of decades, resides in physical (magnetic) enhancement, with magnetic field gradients aligned non-parallel to the direction of flow in the tumor vasculature, of existing passive mechanisms for extravasation and accumulation of MNP in the tumor interstitial fluid, followed by MNP internalization. In this review, we will assess the most recent developments and current status of this approach, considering MNP that are composed of one or more of the three elements that are ferromagnetic at physiological temperature: nickel, cobalt and iron. The effects on cellular functions in vitro, the ability to successfully vector the platform in vivo, the anti-tumor effects of such localized nano-vectors, and any associated toxicities for these MNP will be presented. The merits and shortcomings of nanomaterials made of each of the three elements will be highlighted, and a roadmap for moving this long-established approach forward to clinical evaluation will be put forth. © 2012 Elsevier Ireland Ltd. All rights reserved.
Klostergaard J.,University of Houston |
Bankson J.,University of Houston |
Woodward W.,University of Houston |
Gibson D.,NanoBioMagnetics Inc. |
Seeney C.,NanoBioMagnetics Inc.
AIP Conference Proceedings | Year: 2010
We propose that physical targeting of therapeutics to tumors using magnetically-responsive nanoparticles (MNPs) will enhance intratumoral drug levels compared to free drugs in an effort to overcome tumor resistance. We evaluated the feasibility of magnetic enhancement of tumor extravasation of systemically-administered MNPs in human xenografts implanted in the mammary fatpads of nude mice. Mice with orthotopic tumors were injected systemically with MNPs, with a focused magnetic field juxtaposed over the tumor. Magnetic resonance imaging and scanning electron microscopy both indicated successful tumor localization of MNPs. Next, MNPs were modified with poly-ethylene-glycol (PEG) and their clearance compared by estimating signal attenuation in liver due to iron accumulation. The results suggested that PEG substitution could retard the rate of MNP plasma clearance, which may allow greater magnetically-enhanced tumor localization. We propose that this technology is clinically scalable to many types of both superficial as well as some viscerable tumors with existing magnetic technology. © 2010 American Institute of Physics.
Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 99.97K | Year: 2010
This Small Business Innovation Research (SBIR) Phase I project aims to develop a tumor-specific delivery technology based on the use of superparamagnetic nanoparticles as vehicles for the delivery of paclitaxel. The magnetic vectoring drug delivery platform uses external shaped magnetic field gradients to concentrate nanoparticle-drug constructs at a target site, followed by tumor extravasation. This project will focus on the treatment of superficial tumors, such as locally advanced breast cancers (LABC). These tumors pose a difficult and, as yet, unresolved clinical problem as most patients presenting with this disease will experience resistance and pronounced toxicity for current therapeutics. Therefore, a significant need exists for advanced therapies that can improve patient outcomes. A key distinguishing feature of this technology is the potential to overcome tumor interstitial pressure that normally tends to thwart free drug penetration.
The broader/commercial impact of this project will be the potential to provide localized delivery of therapeutics in a manner that improves both therapeutic and economic benefits to patients. The urgency for such advanced delivery methods is increasing as new classes of pharmaceuticals, such as siRNAs and stem cells, are being developed and brought to market. Because these new therapeutics are more effective through localized therapy, advanced delivery systems that support their full therapeutic potential must be developed. The capacity to magnetically vector therapeutics, tumor-specifically, will have a significant impact on both patient treatment strategies and outcomes.