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Magnetically Controllable Polymer Nanotubes from a Cyclized Crosslinker for Site-Specific Delivery of Doxorubicin.

Newland B, Leupelt D, Zheng Y, Thomas LS, Werner C, Steinhart M, Wang W - Sci Rep (2015)

Bottom Line: Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency.Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template.Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Centre for Biomaterials Dresden, Hohe Straße. 6, Dresden 01069, Germany.

ABSTRACT
Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency. The aim of this work was to develop a nanoscale drug carrier, which could be loaded with an anti-cancer drug and be directed by an external magnetic field. Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template. These polymer nanotubes (PNT) could be functionalized with iron oxide nanoparticles for magnetic manipulation, without affecting the large internal pore, or inherent low toxicity. Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes. Lastly, doxorubicin could be loaded to the PNTs, causing increased toxicity towards neuroblastoma cells, rendering a platform technology now ready for adaptation with different nanoparticles, degradable pre-polymers, and various therapeutics.

No MeSH data available.


Related in: MedlinePlus

Magnetically controlled nanotubes can be directed within a well plate.Light microscope images of doxorubicin loaded magnetically functionalized nanotube clusters, which, in the absence of an external magnetic field spread evenly across a well plate (a). In contrast, doxorubicin loaded magnetic nanotubes can be guided away from one side of the well (upper image of (b)) towards the opposite side of the same well (lower image of (b). This could be repeated in different directions ((c) and SI Figure S14) depending on the placement of the external magnetic field (example images from 6 replicates, scale bars = 200 μm).
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f7: Magnetically controlled nanotubes can be directed within a well plate.Light microscope images of doxorubicin loaded magnetically functionalized nanotube clusters, which, in the absence of an external magnetic field spread evenly across a well plate (a). In contrast, doxorubicin loaded magnetic nanotubes can be guided away from one side of the well (upper image of (b)) towards the opposite side of the same well (lower image of (b). This could be repeated in different directions ((c) and SI Figure S14) depending on the placement of the external magnetic field (example images from 6 replicates, scale bars = 200 μm).

Mentions: Non-functionalized nanotubes typically show an even spread across the cell monolayer (Supplementary Information Fig. 13). Functionalized nanotubes also show this even spread in the absence of an external magnetic field (Fig. 7a); however, the placement of the well plate upon a magnetic stirrer begins to drive the nanotubes in the direction determined by the magnetic field (see Supplementary Information Video 1). The nanotubes collect over at one side of the well plate (Fig. 7b,c, and Supplementary Information Fig. 14), which, despite an initial even covering, results in the opposite side of the well being completely devoid of nanotubes. These experiments highlight the ability of these nanotubes to be targeted to specific regions of cells in vitro, showing that the toxic effects of the doxorubicin can be localized instead of spread throughout the well. Finally, we show that doxorubicin released from non-functionalized and functionalized doxorubicin loaded nanotubes can be up-taken by the neuroblastoma cells by fluorescent microscopy without the up-take of the nanotubes themselves (Fig. 8 and Supplementary Information Fig. 15). At the highest concentration (240 μg/mL) most cells were shown to have up-taken doxorubicin as green fluorescence can be seen co-localizing with the cell regions shown by the brightfield images. However, at this concentration, empty nanotubes fluorescently labelled with fluorescein could be observed in the vicinity of the cells, but not within the lysosomes (indicated by LysoTracker® Deep Red, Life Technologies). This important finding indicates that the polymer nanotubes can act as a nanoscale carrier to deliver doxorubicin to cells without cell uptake or associated complications.


Magnetically Controllable Polymer Nanotubes from a Cyclized Crosslinker for Site-Specific Delivery of Doxorubicin.

Newland B, Leupelt D, Zheng Y, Thomas LS, Werner C, Steinhart M, Wang W - Sci Rep (2015)

Magnetically controlled nanotubes can be directed within a well plate.Light microscope images of doxorubicin loaded magnetically functionalized nanotube clusters, which, in the absence of an external magnetic field spread evenly across a well plate (a). In contrast, doxorubicin loaded magnetic nanotubes can be guided away from one side of the well (upper image of (b)) towards the opposite side of the same well (lower image of (b). This could be repeated in different directions ((c) and SI Figure S14) depending on the placement of the external magnetic field (example images from 6 replicates, scale bars = 200 μm).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664922&req=5

f7: Magnetically controlled nanotubes can be directed within a well plate.Light microscope images of doxorubicin loaded magnetically functionalized nanotube clusters, which, in the absence of an external magnetic field spread evenly across a well plate (a). In contrast, doxorubicin loaded magnetic nanotubes can be guided away from one side of the well (upper image of (b)) towards the opposite side of the same well (lower image of (b). This could be repeated in different directions ((c) and SI Figure S14) depending on the placement of the external magnetic field (example images from 6 replicates, scale bars = 200 μm).
Mentions: Non-functionalized nanotubes typically show an even spread across the cell monolayer (Supplementary Information Fig. 13). Functionalized nanotubes also show this even spread in the absence of an external magnetic field (Fig. 7a); however, the placement of the well plate upon a magnetic stirrer begins to drive the nanotubes in the direction determined by the magnetic field (see Supplementary Information Video 1). The nanotubes collect over at one side of the well plate (Fig. 7b,c, and Supplementary Information Fig. 14), which, despite an initial even covering, results in the opposite side of the well being completely devoid of nanotubes. These experiments highlight the ability of these nanotubes to be targeted to specific regions of cells in vitro, showing that the toxic effects of the doxorubicin can be localized instead of spread throughout the well. Finally, we show that doxorubicin released from non-functionalized and functionalized doxorubicin loaded nanotubes can be up-taken by the neuroblastoma cells by fluorescent microscopy without the up-take of the nanotubes themselves (Fig. 8 and Supplementary Information Fig. 15). At the highest concentration (240 μg/mL) most cells were shown to have up-taken doxorubicin as green fluorescence can be seen co-localizing with the cell regions shown by the brightfield images. However, at this concentration, empty nanotubes fluorescently labelled with fluorescein could be observed in the vicinity of the cells, but not within the lysosomes (indicated by LysoTracker® Deep Red, Life Technologies). This important finding indicates that the polymer nanotubes can act as a nanoscale carrier to deliver doxorubicin to cells without cell uptake or associated complications.

Bottom Line: Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency.Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template.Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Centre for Biomaterials Dresden, Hohe Straße. 6, Dresden 01069, Germany.

ABSTRACT
Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency. The aim of this work was to develop a nanoscale drug carrier, which could be loaded with an anti-cancer drug and be directed by an external magnetic field. Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template. These polymer nanotubes (PNT) could be functionalized with iron oxide nanoparticles for magnetic manipulation, without affecting the large internal pore, or inherent low toxicity. Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes. Lastly, doxorubicin could be loaded to the PNTs, causing increased toxicity towards neuroblastoma cells, rendering a platform technology now ready for adaptation with different nanoparticles, degradable pre-polymers, and various therapeutics.

No MeSH data available.


Related in: MedlinePlus