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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

Schematic diagram depicting the facile route to polymer nanotube preparation, via photocrosslinking the knot polymers within AAO pores followed by template dissolution in sodium hydroxide.
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f2: Schematic diagram depicting the facile route to polymer nanotube preparation, via photocrosslinking the knot polymers within AAO pores followed by template dissolution in sodium hydroxide.

Mentions: Figure 2 shows the simple process used to synthesize the nanotubes, whereby the polymer is dissolved in a solvent, added to the template surface, and exposed to UV light. Figure 3a shows the “small” template, used to synthesize nanotubes of 200 nm diameter and Fig. 3b shows the nanotubes which have been released from the template by the addition of NaOH. Figures 3c and 1d show that the diameter and length of the nanotubes can be adjusted by varying the pore size of the AAO template used (length distributions shown in Fig. 3e). The “small” and “large” templates have pores suitable for the production of tubes with diameters of approximately 230 nm and 350 nm respectively as shown in Figs 3f and 1g respectively. Many tubes have a curved but regular morphology, with predominantly “open” ends, but with the occasional “test tube” like closed end as shown in Fig. 3g. One explanation for the formation of hollow tubes instead of solid nanowires is that the template is rapidly wetted by the pre-polymer mix in acetone (Supplementary Information Fig. 4), but the acetone evaporates quickly leaving the pre-polymer on the pore wall prior to crosslinking. Wall defects are rare (Supplementary Information Fig. 5) but may occur where the pore filling results in only a thin layer of polymer. Whilst explaining the difference in diameter between the “small” and “large” nanotubes is straightforward (i.e. it is dependent on the pore diameter of the template) the reason that the length distributions typically vary is less clear. Perhaps the mechanical stability of the smaller nanotubes is lower than that of the large nanotubes due to the greater confinement within the smaller pores suppressing the intermolecular entanglements or crosslinks. It was therefore desired to analyze if varying the pore depth of the template could alter the length distribution of the nanotubes. For this study, a standard deep pore “large” template (100 μm) was used to synthesize nanotubes which were compared with nanotubes produced in a shallow pore “large” template with a depth of 10 μm. This should, in theory, restrict the maximum nanotube length to 10 μm. Supplementary Information Fig. 6 shows that this restricted pore depth does indeed reduce the length distributions with a limited length dependent on the depth of the pore, but does not produce an exact predetermined nanotube length. The majority of tubes for either template are between 2–4 μm in length probably in part due to mechanical instability, in-complete template wetting (more layers could be applied in future), or breaking during template dissolution. However, since aspect ratio is likely to affect toxicity, this is a precise way to set a maximal length of the nanotubes.


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)

Schematic diagram depicting the facile route to polymer nanotube preparation, via photocrosslinking the knot polymers within AAO pores followed by template dissolution in sodium hydroxide.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Schematic diagram depicting the facile route to polymer nanotube preparation, via photocrosslinking the knot polymers within AAO pores followed by template dissolution in sodium hydroxide.
Mentions: Figure 2 shows the simple process used to synthesize the nanotubes, whereby the polymer is dissolved in a solvent, added to the template surface, and exposed to UV light. Figure 3a shows the “small” template, used to synthesize nanotubes of 200 nm diameter and Fig. 3b shows the nanotubes which have been released from the template by the addition of NaOH. Figures 3c and 1d show that the diameter and length of the nanotubes can be adjusted by varying the pore size of the AAO template used (length distributions shown in Fig. 3e). The “small” and “large” templates have pores suitable for the production of tubes with diameters of approximately 230 nm and 350 nm respectively as shown in Figs 3f and 1g respectively. Many tubes have a curved but regular morphology, with predominantly “open” ends, but with the occasional “test tube” like closed end as shown in Fig. 3g. One explanation for the formation of hollow tubes instead of solid nanowires is that the template is rapidly wetted by the pre-polymer mix in acetone (Supplementary Information Fig. 4), but the acetone evaporates quickly leaving the pre-polymer on the pore wall prior to crosslinking. Wall defects are rare (Supplementary Information Fig. 5) but may occur where the pore filling results in only a thin layer of polymer. Whilst explaining the difference in diameter between the “small” and “large” nanotubes is straightforward (i.e. it is dependent on the pore diameter of the template) the reason that the length distributions typically vary is less clear. Perhaps the mechanical stability of the smaller nanotubes is lower than that of the large nanotubes due to the greater confinement within the smaller pores suppressing the intermolecular entanglements or crosslinks. It was therefore desired to analyze if varying the pore depth of the template could alter the length distribution of the nanotubes. For this study, a standard deep pore “large” template (100 μm) was used to synthesize nanotubes which were compared with nanotubes produced in a shallow pore “large” template with a depth of 10 μm. This should, in theory, restrict the maximum nanotube length to 10 μm. Supplementary Information Fig. 6 shows that this restricted pore depth does indeed reduce the length distributions with a limited length dependent on the depth of the pore, but does not produce an exact predetermined nanotube length. The majority of tubes for either template are between 2–4 μm in length probably in part due to mechanical instability, in-complete template wetting (more layers could be applied in future), or breaking during template dissolution. However, since aspect ratio is likely to affect toxicity, this is a precise way to set a maximal length of the nanotubes.

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