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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 depiction ((a,c) insert) of functionalizing the nanotubes with magnetite.TEM images of: (b) magnetite nanoparticles, (c) a functionalized nanotube with a magnetic end, (d,e) sample images of magnetic nanotubes before magnetic filter separation and, (f) magnetically functionalized nanotubes after purification.
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f5: Schematic depiction ((a,c) insert) of functionalizing the nanotubes with magnetite.TEM images of: (b) magnetite nanoparticles, (c) a functionalized nanotube with a magnetic end, (d,e) sample images of magnetic nanotubes before magnetic filter separation and, (f) magnetically functionalized nanotubes after purification.

Mentions: The process of filling the nanotubes with ferric oxide (Fe2O3) is depicted in Fig. 5a, where Fe2O3 nanoparticles are added into the polymer solution prior to crosslinking. A previous study into the formation of microscale magnetic manipulators used electrospinning to form polymer fibers containing superparamagnetic cobalt nanoparticles26. Although they demonstrated the connection of hippocampal neurons, the materials produced were micron scale, not hollow, and had to be cut into sections with a razor. Here we use an in situ filling mechanism that allows tube formation and magnetic functionalization. TEM analysis of the nanoparticles alone (Fig. 5b) shows a range of sizes but all are far below the 200 nm pores of the smallest AAO template used. Nanotubes could be produced which contained Fe2O3 at one end as shown in Fig. 5c–e. However, approximately half of the nanotubes appeared not to be functionalized as no nanoparticles could be observed at the tube ends. To sort the magnetic nanotubes from the non-magnetic nanotubes, a magnetic cell sorter was used (Supplementary Information Fig. 11). In this way, nanotubes containing Fe2O3 were attracted to the filter (under the effect of an external magnetic field) whilst the non-functionalized nanotubes passed through. After removal of the external magnetic field the functionalized nanotubes could be passed into a separate Eppendorf tube. 46% of the nanotubes were functionalized (Supplementary Information Fig. 11) and collected for subsequent analysis with Fig. 5f showing three such tubes together. Since none of the TEM images of the functionalized tubes either before or after filtration sorting showed free nanoparticles it can be assumed that all were incorporated during the photo-crosslinking. Thus an approximation of the weight percentage of Fe2O3 per nanotubes can be calculated from the average weight of the functionalized nanotube pellet. The value of 2.7 wt% Fe2O3 incorporation can only be taken as an approximation across the average of six batches of functionalized nanotubes. Since only about a half of the nanotubes was functionalized and only at one end, it would suggest that infiltration of the Fe2O3 nanoparticles into the template pores is poor and would have to be further improved if a greater weight percentage of Fe2O3 was desired.


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 depiction ((a,c) insert) of functionalizing the nanotubes with magnetite.TEM images of: (b) magnetite nanoparticles, (c) a functionalized nanotube with a magnetic end, (d,e) sample images of magnetic nanotubes before magnetic filter separation and, (f) magnetically functionalized nanotubes after purification.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Schematic depiction ((a,c) insert) of functionalizing the nanotubes with magnetite.TEM images of: (b) magnetite nanoparticles, (c) a functionalized nanotube with a magnetic end, (d,e) sample images of magnetic nanotubes before magnetic filter separation and, (f) magnetically functionalized nanotubes after purification.
Mentions: The process of filling the nanotubes with ferric oxide (Fe2O3) is depicted in Fig. 5a, where Fe2O3 nanoparticles are added into the polymer solution prior to crosslinking. A previous study into the formation of microscale magnetic manipulators used electrospinning to form polymer fibers containing superparamagnetic cobalt nanoparticles26. Although they demonstrated the connection of hippocampal neurons, the materials produced were micron scale, not hollow, and had to be cut into sections with a razor. Here we use an in situ filling mechanism that allows tube formation and magnetic functionalization. TEM analysis of the nanoparticles alone (Fig. 5b) shows a range of sizes but all are far below the 200 nm pores of the smallest AAO template used. Nanotubes could be produced which contained Fe2O3 at one end as shown in Fig. 5c–e. However, approximately half of the nanotubes appeared not to be functionalized as no nanoparticles could be observed at the tube ends. To sort the magnetic nanotubes from the non-magnetic nanotubes, a magnetic cell sorter was used (Supplementary Information Fig. 11). In this way, nanotubes containing Fe2O3 were attracted to the filter (under the effect of an external magnetic field) whilst the non-functionalized nanotubes passed through. After removal of the external magnetic field the functionalized nanotubes could be passed into a separate Eppendorf tube. 46% of the nanotubes were functionalized (Supplementary Information Fig. 11) and collected for subsequent analysis with Fig. 5f showing three such tubes together. Since none of the TEM images of the functionalized tubes either before or after filtration sorting showed free nanoparticles it can be assumed that all were incorporated during the photo-crosslinking. Thus an approximation of the weight percentage of Fe2O3 per nanotubes can be calculated from the average weight of the functionalized nanotube pellet. The value of 2.7 wt% Fe2O3 incorporation can only be taken as an approximation across the average of six batches of functionalized nanotubes. Since only about a half of the nanotubes was functionalized and only at one end, it would suggest that infiltration of the Fe2O3 nanoparticles into the template pores is poor and would have to be further improved if a greater weight percentage of Fe2O3 was desired.

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