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이규리,Allan E. David,Jian Zhang,신명철,Victor C. Yang 한국공업화학회 2017 Journal of Industrial and Engineering Chemistry Vol.54 No.-
Magnetic iron oxide nanoparticles (MIONs) have received much attention due to their unique properties such as ferromagnetic and superparamagnetic characters. These magnetic properties enable the broad use of MIONs in biomedical applications including magnetic resonance imaging (MRI), magnetically guided delivery, and hyperthermal therapy. In particular, magnetic field guided delivery systems have shown promising potential in the development of targeted drug delivery systems for brain tumors. This system facilitates the extravasation and accumulation of MIONs within the brain tumor under external magnetic field. However, the practical use of MIONs is highly limited due to the large physical size of MIONs required for the sufficient retention and accumulation of particles in the brain tumor. This study aims to enhance the accumulation and retention of MIONs in the brain tumor by in situ formation of large clusters of MIONs. To achieve this goal, MIONs with core size of 100 nm were modified with free thiol end groups by conjugating bi-functional poly(ethylene glycol) (NHS-PEG-SH). It is expected that the prepared MIONs-PEG-SH remain stable during the systemic circulation. When the circulating MIONs-PEG-SH are exposed to the external magnetic field applied to the brain tumor, the local concentration of MIONs-PEGSH can be increased and subsequent interactions among MIONs induce a disulfide bond formation. As a result, in situ formation of the large clusters of MIONs allows enhanced accumulation and retention of MIONs in a rat brain tumor model. Moreover, when doxorubicin is loaded onto the MIONs, the biodistribution of doxorubicin at brain tumor site is highly enhanced, suggesting their potential use in theranostic applications.
Chertok, Beata,David, Allan E.,Yang, Victor C. Elsevier 2011 Journal of controlled release Vol.155 No.3
<P><B>Abstract</B></P><P>Our previous studies demonstrated feasibility of magnetically-mediated retention of iron oxide nanoparticles in brain tumors after intravascular administration. The purpose of this study was to elucidate strategies for further improvement of this promising approach. In particular, we explored administration of the nanoparticles via a non-occluded carotid artery as a way to increase the passive exposure of tumor vasculature to nanoparticles for subsequent magnetic entrapment. However, aggregation of nanoparticles in the afferent vasculature interfered with tumor targeting. The magnetic setup employed in our experiments was found to generate a relatively uniform magnetic flux density over a broad range, exposing the region of the afferent vasculature to high magnetic force. To overcome this problem, the magnetic setup was modified with a 9-mm diameter cylindrical NdFeB magnet to exhibit steeper magnetic field topography. Six-fold reduction of the magnetic force at the injection site, achieved with this modification, alleviated the aggregation problem under the conditions of intact carotid blood flow. Using this setup, carotid administration was found to present 1.8-fold increase in nanoparticle accumulation in glioma compared to the intravenous route at 350mT. This increase was found to be in reasonable agreement with the theoretically estimated 1.9-fold advantage of carotid administration, <I>R</I><SUB><I>d</I></SUB>. The developed approach is expected to present an even greater advantage when applied to drug-loaded nanoparticles exhibiting higher values of <I>R</I><SUB><I>d</I></SUB>.</P> <P><B>Graphical abstract</B></P><P><ce:figure id='f0035'></ce:figure></P>
Nanoparticles for gene delivery: therapeutic and toxic effects
Choi, Young Suk,Lee, Mi Young,David, Allan E.,Park, Yoon Shin 대한독성유전단백체학회 2014 Molecular & cellular toxicology Vol. No.
Gene therapy has drawn significant attention as a potential method for treating both acute illnesses and chronic diseases. Current research efforts have focused on developing carriers that effectively compact and protect naked DNA, RNA and siRNA, which are rapidly degraded by enzymes in the blood. As an alternative to viral and polymeric carriers, nano-particles have been introduced as promising carriers with low toxicity profiles and well-controlled gene delivery efficiency. While significant advances have been made for in vitro applications, much still remains to be done, especially for in vivo translation. Here we provide a concise review on the development of nano-particles for gene delivery.
Park, Yoon Shin,Huang, Yongzhuo,Park, Yoon Jeong,David, Allan E.,White, Lindsay,He, Huining,Chung, Hee Sun,Yang, Victor C. Elsevier 2010 Journal of controlled release Vol.144 No.1
<P><B>Abstract</B></P><P>Hypoxia is a strong modulator of angiogenesis, accelerating adipose tissue expansion, suggesting that hypoxia inducible factor 1α (HIF1α) can be a novel target for anti-obesity. We conjugated antisense-HIF1α-oligonucleotide (ASO) with low molecular weight protamine (LMWP), a cell-penetrating peptide, to enhance its ability to block hypoxic-angiogenesis, thereby eliciting an anti-obesity effect. Nano-sized ASO-LMWP (AS-L) conjugates enhanced cellular uptake of ASO without yielding a cytotoxic effect and protected the ASO against enzymatic attack and chemical reduction. AS-L showed enhanced intra-cellular localization compared to naked ASO and the complex of ASO with lipofectamine during hypoxic-differentiation. Consequently AS-L induced significant down-regulation of leptin and VEGF gene expressions, thereby reducing fat accumulation in the cell.</P><P>This proof-of-concept study shows that AS-L produces an inhibitory effect on adipogenesis and angiogenesis during differentiation, indicating LMWP mediated ASO delivery can potentially be a safe and promising treatment for obesity.</P> <P><B>Graphical abstract</B></P><P></P>