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Development of Janus Nanocomposites as a Multifunctional Nanocarrier for Cancer Therapy

Wang, Feng
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1393236316

Abstract Details

2013, PhD, University of Cincinnati, Engineering and Applied Science: Materials Science.
With the advancement of nanotechnology, cancer therapy requires that the carrier at nanoscale integrates cell targeting, imaging, drug storage and controlled drug release simultaneously. Extensive efforts have been devoted to isotropic sphere nanoparticle based carrier systems for their uniform surface properties. However, multifunctionality also leads to a challenge issue: different moieties may interfere with each other in bioconjugation process due to the similar conjugation chemistry applied to the same surface. As a result, Janus nanoparticles which are anisotropic in shape, composition or surface chemistry have attracted increasing attention. Asymmetric composition could achieve multifunctionality simultaneously. More importantly, surfaces could be selectively loaded with targeting ligands, imaging probes or drugs, which made the Janus nanoparticles “truly multifunctional entities”. A variety of fabrication methods have been studied to synthesize Janus nanoparticles for applications such as surfactants, magnetic-fluorescent display or imaging, and catalysts, etc. In contrast, exploration in the biomedical application field is rather limited. Based on our previous work on iron oxides@polystyrene matrix multifunctional nanoparticles and yolk-shell nanocomposites, we designed the polystyrene/Fe3O4@SiO2 superparamagnetic Janus nanocomposites (SJNCs). The SJNCs (~300 nm) are composed of a polystyrene (PS) core and a silica half shell embedded with iron oxide nanoparticles. We demonstrated the innovative dual functionalities on independent surfaces were obtained simultaneously during one-pot facile synthesis, which is much more convenient than the previous report on generating the similar structure through selectively coating. PS surfaces were decorated with carboxyl groups and silanol groups on silica surfaces provided enormous opportunities for further functionalization. To achieve cell targeting and controlled drug release, we conjugated folic acid (FA) to the PS and doxorubicin (DOX), an anti-cancer drug to the silica via a pH-sensitive hydrazone bond (FA-SJNCs-DOX). Drug release behaviors in different buffer solutions (pH 5.0, 6.0 and 7.4) displayed clear pH dependence. To evaluate the in vitro cell targeting and drug release, cell cytotoxicity of FA-SJNCs-DOX against human breast cancer line MDA-MB-231 was tested. Significant difference of the concentrations killing 50 % of the cells (IC50) was observed from targeted and non-targeted group. It is hypothesized that targeted nanocomposites (FA-SJNCs-DOX) could be internalized by cancer cells via folate receptor mediated endocytosis and release the drug at a faster rate in endocytic compartments (pH 4.5~6.5), compared to under physiological condition (pH 7.4) from the non-targeted group (SJNCs-DOX), thus providing highly localized controlled drug delivery. More interestingly, the incorporated iron oxides could provide potential application such as MRI, magnetic targeting and hyperthermia, thus making the Janus nanocomposites a truly versatile platform for wide biomedical application.
Donglu Shi, Ph.D. (Committee Chair)
Vikram Kuppa, Ph.D. (Committee Member)
Giovanni Pauletti, Ph.D. (Committee Member)
Vesselin Shanov, Ph.D. (Committee Member)
128 p.
Materials Science
Janus; Nanocomposites; Surface functionalization; Cancer therapy

Recommended Citations

Citations

  • Wang, F. (2013). Development of Janus Nanocomposites as a Multifunctional Nanocarrier for Cancer Therapy [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1393236316

    APA Style (7th edition)

  • Wang, Feng. Development of Janus Nanocomposites as a Multifunctional Nanocarrier for Cancer Therapy. 2013. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1393236316.

    MLA Style (8th edition)

  • Wang, Feng. "Development of Janus Nanocomposites as a Multifunctional Nanocarrier for Cancer Therapy." Doctoral dissertation, University of Cincinnati, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1393236316

    Chicago Manual of Style (17th edition)

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© 2013, some rights reserved.Creative Commons License Development of Janus Nanocomposites as a Multifunctional Nanocarrier for Cancer Therapy by Feng Wang is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.