Publications by authors named "Christopher J Dayringer"

3 Publications

  • Page 1 of 1

Biconcave Carbon Nanodisks for Enhanced Drug Accumulation and Chemo-Photothermal Tumor Therapy.

Adv Healthc Mater 2019 04 11;8(8):e1801505. Epub 2019 Mar 11.

Department of Materials Science and Engineering, University of Washington, Seattle, Washington, DC, 98195, USA.

It is considered a significant challenge to construct nanocarriers that have high drug loading capacity and can overcome physiological barriers to deliver efficacious amounts of drugs to solid tumors. Here, the development of a safe, biconcave carbon nanodisk to address this challenge for treating breast cancer is reported. The nanodisk demonstrates fluorescent imaging capability, an exceedingly high loading capacity (947.8 mg g , 94.78 wt%) for doxorubicin (DOX), and pH-responsive drug release. It exhibits a higher uptake rate by tumor cells and greater accumulation in tumors in a mouse model than its carbon nanosphere counterpart. In addition, the nanodisk absorbs and transforms near-infrared (NIR) light to heat, which enables simultaneous NIR-responsive drug release for chemotherapy and generation of thermal energy for tumor cell destruction. Notably, this NIR-activated dual therapy demonstrates a near complete suppression of tumor growth in a mouse model of triple-negative breast cancer when DOX-loaded nanodisks are administered systemically.
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http://dx.doi.org/10.1002/adhm.201801505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483846PMC
April 2019

Approach to Rapid Synthesis and Functionalization of Iron Oxide Nanoparticles for High Gene Transfection.

ACS Appl Mater Interfaces 2016 Mar 4;8(10):6320-8. Epub 2016 Mar 4.

Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.

Surface functionalization of theranostic nanoparticles (NPs) typically relies on lengthy, aqueous postsynthesis labeling chemistries that have limited ability to fine-tune surface properties and can lead to NP heterogeneity. The need for a rapid, simple synthesis approach that can provide great control over the display of functional moieties on NP surfaces has led to increased use of highly selective bioorthoganol chemistries including metal-affinity coordination. Here we report a simple approach for rapid production of a superparamagnetic iron oxide NPs (SPIONs) with tunable functionality and high reproducibility under aqueous conditions. We utilize the high affinity complex formed between catechol and Fe((III)) as a means to dock well-defined catechol modified polymer modules on the surface of SPIONs during sonochemical coprecipitation synthesis. Polymer modules consisted of chitosan and poly(ethylene glycol) (PEG) copolymer (CP) modified with catechol (CCP), and CCP functionalized with cationic polyethylenimine (CCP-PEI) to facilitate binding and delivery of DNA for gene therapy. This rapid synthesis/functionalization approach provided excellent control over the extent of PEI labeling, improved SPION magnetic resonance imaging (MRI) contrast enhancement and produced an efficient transfection agent.
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http://dx.doi.org/10.1021/acsami.5b10883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829641PMC
March 2016

Nanoparticle mediated silencing of DNA repair sensitizes pediatric brain tumor cells to γ-irradiation.

Mol Oncol 2015 Jun 29;9(6):1071-80. Epub 2015 Jan 29.

Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA; Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA; Department of Radiology, University of Washington, Seattle, WA 98195, USA. Electronic address:

Medulloblastoma (MB) and ependymoma (EP) are the most common pediatric brain tumors, afflicting 3000 children annually. Radiotherapy (RT) is an integral component in the treatment of these tumors; however, the improvement in survival is often accompanied by radiation-induced adverse developmental and psychosocial sequelae. Therefore, there is an urgent need to develop strategies that can increase the sensitivity of brain tumors cells to RT while sparing adjacent healthy brain tissue. Apurinic endonuclease 1 (Ape1), an enzyme in the base excision repair pathway, has been implicated in radiation resistance in cancer. Pharmacological and specificity limitations inherent to small molecule inhibitors of Ape1 have hindered their clinical development. Here we report on a nanoparticle (NP) based siRNA delivery vehicle for knocking down Ape1 expression and sensitizing pediatric brain tumor cells to RT. The NP comprises a superparamagnetic iron oxide core coated with a biocompatible, biodegradable coating of chitosan, polyethylene glycol (PEG), and polyethyleneimine (PEI) that is able to bind and protect siRNA from degradation and to deliver siRNA to the perinuclear region of target cells. NPs loaded with siRNA against Ape1 (NP:siApe1) knocked down Ape1 expression over 75% in MB and EP cells, and reduced Ape1 activity by 80%. This reduction in Ape1 activity correlated with increased DNA damage post-irradiation, which resulted in decreased cell survival in clonogenic assays. The sensitization was specific to therapies generating abasic lesions as evidenced by NP:siRNA not increasing sensitivity to paclitaxel, a microtubule disrupting agent. Our results indicate NP-mediated delivery of siApe1 is a promising strategy for circumventing pediatric brain tumor resistance to RT.
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http://dx.doi.org/10.1016/j.molonc.2015.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439369PMC
June 2015
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